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WO2019112383A1 - Metal mineral diaminate and preparation method therefor - Google Patents

Metal mineral diaminate and preparation method therefor Download PDF

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Publication number
WO2019112383A1
WO2019112383A1 PCT/KR2018/015552 KR2018015552W WO2019112383A1 WO 2019112383 A1 WO2019112383 A1 WO 2019112383A1 KR 2018015552 W KR2018015552 W KR 2018015552W WO 2019112383 A1 WO2019112383 A1 WO 2019112383A1
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WO
WIPO (PCT)
Prior art keywords
aspartate
glutamate
amino acid
bisaspartate
bisglutamate
Prior art date
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PCT/KR2018/015552
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French (fr)
Korean (ko)
Inventor
윤주석
김누리
Original Assignee
윤주석
주식회사 휴엔
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Application filed by 윤주석, 주식회사 휴엔 filed Critical 윤주석
Priority claimed from KR1020180156669A external-priority patent/KR102010558B1/en
Publication of WO2019112383A1 publication Critical patent/WO2019112383A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
    • C07F1/08—Copper compounds

Definitions

  • the present invention relates to a metal mineral dianimate and a novel process for producing the same, wherein a metal mineral source and a mono-molecular amino acid are reacted in an aqueous solution, selectively filtered, concentrated and dried under reduced pressure or spray-
  • the present invention relates to a method for producing a metallic mineral diamine which does not occur. More specifically, the present invention relates to a method for producing a metal mineral dianimide which is electrically neutral and has no byproducts by preparing a metal mineral source and an acidic amino acid by reacting them in an aqueous solution or by reacting a metal mineral source with an amino acid in an acidic aqueous solution .
  • Minerals are the main constituent of the body, and they are essential nutrients that play important physiological control functions such as permeability regulation and metabolism of cell membrane.
  • modern people eat a lot of supplements because it is difficult to consume all the necessary minerals in the body by the diet added to the food.
  • mineral supplements the most important thing when ingesting is absorption rate and utilization rate in vivo, and in order for the minerals to be absorbed to the metal ion in the small intestine, ionized minerals are more absorbed than a single substance.
  • Recent studies have also shown that when minerals are bound to proteins or amino acids, they are absorbed into the small intestine by the absorption pathway of amino acids. Accordingly, many studies on the binding of minerals and amino acids have been conducted, and metallic mineral chelates or mineral diaminates having enhanced bioabsorption rates have been developed.
  • the metal mineral diamine is a compound in which two molecules of amino acid monomers and divalent mineral ions are ionically and coordinately bound to each other.
  • the mineral chelate is a compound in which oligopeptides and mineral ions having about 6 to 10 amino acids are ion- And it means a structure that completely encloses minerals.
  • the minerals diaminate has a stronger binding force than a simple salt in which a mineral is combined with a single amino acid but has weaker binding force than a chelate in which the mineral is completely surrounded, such as a mineral chelate.
  • This difference in binding force shows a bioabsorption rate similar to that of the mineral chelate compound, but the bioavailability is higher than that of the mineral chelate compound.
  • mineral diamine binds mono-molecular amino acid to a single element of mineral, its molecular size is easy to permeate through the cell membrane and is directly absorbed through the barrier, so that the bioabsorption and bioavailability are high.
  • the metal mineral diaminate is a double bond structure of ionic bonding and coordination bonding. It is not decomposed while digestive organs go through, and active absorption occurs in the small intestine. It passes through the stomach and does not go through the same ionization process.
  • Prior Art Korean Patent Registration No. 10-0481326 discloses a method for producing an organic chelate according to claim 1, wherein 1) a salt containing a metal mineral to be coordinated with an amino acid is dissolved in water and then NaOH or KOH is used Thereby precipitating a metal hydroxide; 2) removing the water-soluble K 2 SO 4 , Na 2 SO 4 or KCl, NaCl salt in the aqueous solution with a filter press; 3) dissolving the metal hydroxide of filtered M (OH) 2 (wherein M is a metal ion) with hydrochloric acid; 4) completely dissolving and mixing the amino acid in the solution; 5) After the above mixing, slowly titrating to the pI value of the amino acid with NaOH; And 6) filtering and drying the resulting particles.
  • X is a divalent metal ion and AA is an amino acid.
  • X is a divalent metal ion
  • M is a divalent metal ion other than X
  • AA is an amino acid
  • X is a divalent metal ion and AA is an amino acid.
  • the present inventors have completed the present invention by developing a process for producing metallic mineral diamines that overcomes the above-mentioned problem of by-products.
  • the present invention provides metal mineral diamines and processes for their preparation.
  • the present invention also provides a composition comprising the metal mineral diaminate prepared by the above method in a pharmacologically effective amount, a nutritionally effective amount or a cosmetically effective amount.
  • the present invention also provides a cosmetic composition comprising a uridine or uridine derivative and a metallic mineral diaminate.
  • the present invention relates to a method for producing a metal mineral / mono-molecular amino acid aqueous solution, comprising the steps of: adding a metal mineral source and an amino acid to water at a concentration of 0.1 to 70% by weight; Reacting the prepared metal mineral amino acid aqueous solution under an acidic condition for a predetermined time; Optionally filtering or concentrating the reaction aqueous solution; And drying and pulverizing; And a method for producing the metal mineral diamine.
  • the present invention relates to a method for producing a metal mineral / mono-molecular amino acid aqueous solution, comprising the steps of: adding a metal mineral source and an amino acid to water at a concentration of 0.1 to 70% by weight; Reacting the aqueous solution of the metal mineral and amino acid by heating at 40 to 100 ⁇ with stirring for a certain period of time; Optionally filtering or concentrating the reaction aqueous solution; And drying and pulverizing; As a further means for solving the problems.
  • the metal mineral source solution and the amino acid solution may be mixed at a ratio of 1: 1 to 4 based on the molar ratio of the mineral and amino acid of the metal mineral source.
  • the pH of the metal mineral / amino acid aqueous solution is adjusted to a pH of 4 to 8 by using a buffer solution. I want to.
  • the present invention further provides a process for producing metallic mineral diamines characterized by further comprising the step of pulverizing the metallic mineral-amino acid aqueous solution by vacuum drying, freeze-drying or spray-drying, .
  • the present invention provides a method for producing metal mineral diamines, wherein the metal amino acid is an acidic amino acid.
  • the present invention provides a method for producing metallic mineral diamines, which comprises at least one metal mineral source and at least one amino acid, respectively, to solve the technical problems.
  • the present invention is based on the finding that the metal mineral diaminates are selected from the group consisting of copper glutamate / aspartate, cooper bisglutamate, cooper bisaspartate, zinc glutamate / aspartate, Zinc bisglutamate, zinc bisaspartate, iron glutamate / aspartate, iron bisglutamate, iron bisaspartate, iron bisglutamate, / Iron aspartate, iron glutamate / bisaspartate, chromium glutamate / aspartate, chromium bisglutamate, chromium bisaspartate, ), Chromium bisglutamate / aspartate, aspartate, chromium glutamate / bisaspartate, covalt glutamate / aspartate, covalt bisglutamate, covalt bisaspartate, magnesium glutamate / for example, magnesium glutamate / aspartate, magnesium bisglutamate, magnesium bisaspartate, manganese glutamate
  • the present invention aims to solve the technical problem by providing an electrically neutral metal mineral dianimate produced by the above method.
  • the present invention relates to the above-mentioned metal mineral dianimide, which comprises copper glutamate / aspartate, cooper bisglutamate, cooper bisaspartate, zinc glutamate / aspartate, zinc glutamate / aspartate, ), Zinc bisglutamate, zinc bisaspartate, iron glutamate / aspartate, iron bisglutamate, iron bisaspartate, iron bis
  • the present invention relates to a method for the treatment and / or prophylaxis of an inflammatory disease or condition selected from the group consisting of iron bisglutamate / aspartate, iron glutamate / bisaspartate, chromium glutamate / aspartate, chromium bisglutamate, chromium bisaspartate, bisaspartate, chromium bisglue / aspartate, cobalt bisaspartate, cobalt glutamate / aspartate, cobalt bisglutamate, cobalt bisaspartate,
  • the present invention aims at solving the technical problems by providing an antiinflammatory pharmaceutical composition comprising a uridine or uridine derivative and a metal mineral diamine.
  • the present invention aims at solving technical problems by providing a cosmetic composition comprising a uridine or uridine derivative and a metallic mineral diaminate.
  • the present invention relates to a process for producing a novel metal mineral dianimate by reacting a metal mineral source with an acidic amino acid in an aqueous solution or by reacting a metal mineral source with an amino acid in an acidic aqueous solution, Dried, freeze-dried or spray-dried to produce a metal-mineral dianimide which is electrically neutral and free of byproducts.
  • the present invention relates to a metal mineral dianimate produced by the above method, which maintains stability at a temperature and a pH, does not affect the physical properties and taste of the product, exhibits a high absorption rate in the body, , Feed, and plant growth promoters.
  • FIG. 1 is a view showing the bonding and structural formula of a metallic mineral diaminate.
  • FIG. 2 is a photograph of a zinc aspartate diaminate prepared by spray drying.
  • Figure 3 is a photograph of manganese aspartic acid diaminate prepared by spray drying.
  • 4 is a photograph of calcium glutamic acid diaminate prepared by spray drying.
  • Figure 5 shows the effect of zinc aspartate diaminate on the production of nitric oxide of RAW 264.7 cells treated with lipopolysaccharide.
  • the molar ratio of the minerals to the amino acids in the metal mineral source is 1: 1 to 4, and as the solvent, water can be preferably used. However, if it can be easily removed after the reaction without affecting other reactants, It is not.
  • the solvent may be water, an alkaline solvent, an acidic solvent or an organic solvent. Further, in the case of using a neutral or alkaline amino acid in order to increase the efficiency of the process in an aqueous solution, a buffer solution may be added to satisfy an acidic aqueous solution condition.
  • the pH is preferably adjusted to a pH of from 4 to 8, more preferably from 5 to 7.5, in order to maintain smooth reactivity and neutrality of the product.
  • the reaction temperature is preferably from 0 to 100 ° C, and if the temperature is too low, the reactivity is deteriorated. On the other hand, if the temperature is too high, there is a problem of excessive energy use and a possibility that some amino acids are altered.
  • the metal mineral source that can be used in the present invention is not particularly limited and includes salts of metals having a valence of 2 or more such as calcium, copper, zinc, iron, chromium, cobalt, manganese, magnesium, selenium, , And in some cases, a mixture of two or more thereof may be used.
  • the metallic mineral source include copper sulfate, magnesium carbonate, magnesium lactate, magnesium carbonate, magnesium sulfate, magnesium gluconate, magnesium chloride, manganese sulfate, manganese chloride, zinc oxide, zinc sulfate, zinc gluconate, Calcium ferric oxide, calcium ferric oxide, calcium lactate, calcium carbonate, calcium citrate, calcium phosphate dibasic, calcium hydroxide, tribasic calcium phosphate, calcium gluconate, and chromium chloride.
  • the metal mineral source of the present invention may be a natural or artificially synthesized non-natural metal mineral resource present in nature, or it may be a pharmaceutical raw material, a food raw material, a cosmetic raw material, or an industrial raw material, Or a mixture of two or more thereof.
  • the amino acid which can be used in the present invention is not particularly limited, but in order to satisfy the acidic reaction condition, the amino acid is preferably, for example, glutamic acid or aspartic acid, and may be used in a mixture form of two or more thereof have.
  • the amino acid is not an acidic amino acid such as glutamic acid and aspartic acid, it is preferable to use an acidic aqueous solution. In some cases, a heating process may be required for the production of smooth diaminates.
  • the diamination reaction using the metal mineral source and the amino acid of the present invention can be expressed as shown in the following reaction formula (1).
  • X is a divalent metal ion
  • AA is an amino acid
  • X is a divalent metal ion
  • AA is an amino acid
  • X is a divalent metal ion
  • AA is an amino acid
  • X is a divalent metal ion
  • AA is an amino acid
  • X is a divalent metal ion
  • AA is an amino acid
  • X is a divalent metal ion
  • AA is an amino acid
  • the present invention relates to a metal mineral diamine represented by the following formula (1) or (2) prepared by the above method.
  • M is a divalent metal ion and AA is an amino acid.
  • M ' is a trivalent metal ion and AA is an amino acid.
  • Spray drying technology is a process in which a liquid sample such as a liquid, an organic solution, an emulsion, a dispersion or a suspension is sprayed, atomized, and brought into contact with a hot air stream.
  • the spray dryer is a device for spraying a liquid sample into a fine droplet form, and then evaporating water (water) or an organic solvent using a hot dry gas to produce a powder.
  • Spray drying takes place in a single step of liquid phase drying and has advantages such as cost reduction, easy scale-up, and simplification of processing process.
  • temperature-sensitive materials such as enzymes, proteins, or antibiotics can be pulverized without thermal deformation by using a spray drying technique, in the present invention,
  • the amino acid solution was prepared by powder drying and mineral chelate formation.
  • the sample solution must be pumpable, uniform, and free from impurities such as aqueous solutions, emulsions, suspensions or organic solutions.
  • pretreatment of the sample solution will greatly affect the particle size, shape and particle coating of the final spray product.
  • Additives such as lubricants, defloccants or other special substances must be incorporated into the sample solution in very small amounts.
  • a metal mineral / amino acid aqueous solution prepared by stirring each metal mineral aqueous solution and an amino acid aqueous solution was used as a sample.
  • a variety of nozzles are used to dispense the sample solution to obtain finer droplets.
  • a commonly used type of nozzle is a two fluid nozzle, a pressure nozzle, a rotary disk atomizer, or an ultrasonic nozzle.
  • the inlet temperature (the temperature of the drying gas) can be spray dried at a temperature of 50 to 550 ° C.
  • a metal mineral / amino acid aqueous solution is spray dried at a temperature of preferably 50 to 150 ° C.
  • the selection of the dispensing device takes into account the amount and nature of the sample solution to be treated and the nature of the spray dryer desired to be made.
  • the nozzle is selected according to the particle size of the mineral diamine, which is the final product.
  • a metallic mineral / amino acid aqueous solution prepared by stirring a metallic mineral aqueous solution and an amino acid aqueous solution is pulverized using the above-described spray drying apparatus to prepare a metallic mineral diaminate.
  • Representative amino acid metal mineral diamines that can be prepared through the reaction of the present invention include, but are not limited to, the following.
  • the metal mineral chelate produced by the method described above may be selected from the group consisting of calcium glutamate / aspartate, calcium glutamate / methionine, calcium glutamate / glycine, calcium aspartate / methionine calcium aspartate / methionine, calcium aspartate / glycine, calcium methionine / glycine, calcium bisglutamate, calcium bisaspartate, calcium bis-methionine calcium bismethionine or calcium bisglycine, and furthermore, one or more of these may be combined to produce a new metal mineral diaminate mixture.
  • the metal mineral diaminate is analyzed by the method of 1 FT-IR infrared spectroscopy (metal mineral diamine structure), 3 ICP emission spectrometry (element content measurement), and 3 amino acid analysis (amino acid content measurement) Respectively.
  • the metal mineral diaminate compound obtained in Example 1 was subjected to a safety test according to long-term preservation in an aqueous solution.
  • Experimental conditions were as follows: 1) the pH of the distilled water was adjusted to 3, 5, 7, and 9, the sample was added with the compound, and 2) the pH was adjusted to 3, 5, 7, A sample to which the above compound is added in a commercially available beverage (Vita 500, Bacchus, or Orange juice), 4) a sample in which the compound is added to skin lotion in commercially available cosmetics, 5) A sample in which the compound is added to a plant growth promoter.
  • a commercially available beverage Vita 500, Bacchus, or Orange juice
  • the present invention relates to a composition containing the amino acid diaminate of the above formula (1) or (2) in a pharmaceutical or nutritional or cosmetically effective amount.
  • the metal mineral diaminates of formula (I) or (II) may be formulated into various pharmaceutical dosage forms as desired.
  • the diaminates of formula (I) or (II) may be mixed with various pharmaceutically acceptable carriers which may be selected according to the formulations to be prepared.
  • the pharmaceutical composition according to the present invention can be formulated into injectable or oral formulations as desired.
  • the metal mineral diaminates of formula (I) or (II) as active ingredients can be formulated in a known manner using known pharmaceutical carriers and excipients and incorporated into unit dose forms or multi-dose containers.
  • the formulation form may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, and may contain conventional dispersing agents, suspending agents or stabilizing agents. It may also be in the form of a dry powder, for example, dissolved in sterile, pyrogen-free water before use.
  • the metal mineral diaminates of formula (I) or (II) may also be formulated as suppositories using conventional suppository bases such as corn butter or other glycerides.
  • Solid dosage forms for oral administration may be capsules, tablets, pills, powders, and granules, with capsule and tablet being particularly useful. Tablets and pills are preferably prepared as preservative.
  • the active ingredient metal mineral diaminate of formula (I) or (II) is mixed with one or more inert diluents such as sucrose, lactose, starch and the like, and a lubricant such as magnesium stearate, disintegrants, .
  • the metal mineral diamine of formula (I) or (II) according to the present invention or the composition containing it may be administered in combination with other medicaments.
  • the therapeutically effective amount means the amount of active ingredient effective to reduce or delay the onset of a clinical marker or symptom of a disease that alleviates, reduces or prevents symptoms of the disease requiring treatment.
  • a pharmacologically effective amount can be determined empirically by testing compounds in known in vivo and in vitro model systems for diseases in need of treatment.
  • the metal mineral diamine of formula (I) or (II) as the active ingredient is preferably contained in a unit dose of about 0.1 to 1000 mg.
  • the dosage depends on the physician's prescription depending on factors such as the patient's weight, age and the particular nature and severity of the disease. However, the dosage required for adult therapy is usually in the range of about 1 to 1000 mg per day, depending on the frequency and intensity of administration.
  • a total dosage of about 1 to 500 mg per day, separated by a single dose at the time of intramuscular or intravenous administration to an adult would suffice, but in some patients a higher daily dose may be desirable.
  • &quot cytologically effective amount " means an amount of the active ingredient that is effective for supplementing the nutritional metabolism of an object, which does not lead to disease, but which does not cause side effects due to overdosage.
  • the cosmetically effective amount refers to the amount of the active ingredient that is effective in improving the nutritional status related to the beauty of the object such as the health condition of the skin and the health condition of the hair and at the same time, do.
  • the nutritional effective amount and the cosmetically effective amount may be variably determined by various factors such as the use and properties of the composition to be used, so that the effective amount need not be particularly limited.
  • the composition according to the present invention may contain, depending on its use, for example, a pharmaceutical composition comprising a pharmaceutically acceptable carrier, a food comprising a nutraceutically acceptable carrier, a feed additive or beverage composition, And a cosmetic composition containing a carrier that is acceptable as a cosmetic composition.
  • the mineral diiminate compounds obtained in Experimental Examples 1 to 16 were added to commercially available Mierofhaiba (Hyundai Pharm) to confirm the effect on physical properties and taste.
  • 10 taste sensory evaluations were conducted on the taste, appearance and comprehensive evaluation of the sample aqueous solutions obtained in Experimental Examples 1 to 16 against 10 special sensory test agents.
  • the taste was evaluated by scoring five points of very weak (1), weak (2), normal (3), strong (4), and very strong (5) for bitter taste, pungent taste and strong taste. Color and clarification and comprehensive evaluation were performed in such a way as to score 5 points of very poor (1), poor (2), normal (3), good (4) and excellent (5).
  • the evaluation of taste is shown in Table 1 below, and the evaluation of appearance is shown in Table 2 below.
  • the mineral diiminate compound according to the present invention hardly affected the physical properties (taste, appearance, etc.) of the object to be added.
  • a powder mixture was prepared by mixing 0.5% by weight of 5-ribonucleotide with 99.5% by weight of the diaminate compound of Experimental Example 13, and the taste thereof was confirmed. As a result, it was confirmed that the same taste as that of sodium glutamate Respectively. Therefore, it was confirmed that the diaminate compound of the present invention had no problem in utilization as a seasoning.
  • the mineral diaminate compound obtained in Experimental Example 13 was mixed with 100 g of milk and kept for a long time. As a result, no precipitation was formed and no influence on the taste was observed.
  • the cosmetic lotion type containing the mineral diaminate compound obtained in Experimental Example 1 was prepared and maintained for a long time, and as a result, there was no discoloration and there was no problem even if it was used for skin.
  • Lipopolysaccharide is an outer membrane component of Gram-negative bacteria. When treated with cells, it induces inflammation and induces nitric oxide (NO) production. Since the produced nitric oxide induces inflammatory response to peripheral cells and induces proinflammatory stimulation, inhibition of nitric oxide production is important in the treatment of inflammatory diseases. Therefore, in order to examine the anti-inflammatory effect of the metal mineral diaiminate composite composition containing uridine, the degree of nitric oxide produced after lipopolysaccharide treatment of RAW 264.7 cells treated with the composite composition was observed.
  • RAW 264.7 macrophages used for the anti-inflammatory effect test were distributed from the Korean Cell Line Bank.
  • RAW264.7 macrophages were cultured in Dulbecco's modified Eagle minimal essential medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin and 1% streptomycin , DMEM), and then cultured at 37 ° C under 5% carbon dioxide for 24 hours.
  • the badge was changed every 2 days.
  • the prepared zinc aspartate diaminate was used as a stock solution at a concentration of 1 mg / ml by adding tertiary distilled water and stored at 4 ° C.
  • RAW 264.7 cells were plated at 2.5 ⁇ 10 5 cells / ml in a 24-well plate and cultured at 37 ° C. under 5% carbon dioxide for 24 hours.
  • zinc aspartate diaminate was treated to 25, 50, 100 and 200 ug / ml, respectively, and added to 100 ug / ml of uridine.
  • lipopolysaccharide (LPS) was cultured at 200 ng / ml for 24 hours.
  • RAW 264.7 cells treated with nothing were treated with negative control
  • RAW 264.7 cells treated with only 200 ng / ml of lipopolysaccharide were treated with positive control
  • zinc ascapartate diaminate 25 50, 100 and 200 ug / ml each of uridine
  • RAW 264.7 cells treated with 200 ng / ml of lipopolysaccharide after one hour of treatment with ug / ml were designated Experimental Groups 1, 2, 3 and 4, respectively.
  • Figure 5 shows the effect of zinc aspartate diaminate on the production of nitric oxide of RAW 264.7 cells treated with lipopolysaccharide.
  • uridine derivatives uridine phosphate, uracil, uridine monophosphate, uridine diphosphate, triacetyl uridine, tribenzonyl uridine, uridine, 5-ethyl uridine, 2-deoxyuridine, or isopropylidene uridine may be used.

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Abstract

The present invention relates to a metal mineral diaminate and a novel preparation method therefor and, specifically, to a method for preparing a metal mineral diaminate causing no byproduct by allowing a metal mineral source to react with a monomolecular amino acid in an aqueous solution, followed by selective filtration, concentration, and drying, such as drying under reduced pressure or spray-drying. More specifically, the present invention relates to a method for preparing a metal mineral diaminate, which is electrically neutral and has no byproduct, by preparing the metal mineral diaminate through a reaction of a metal mineral source and an acidic amino acid in an aqueous solution or a reaction of a metal mineral source and an amino acid in an acidic aqueous solution.

Description

금속 미네랄 디아미네이트 및 이의 제조방법METAL MINERAL DIAMONATE AND METHOD FOR PRODUCING THE SAME
본 발명은 금속 미네랄 디아미네이트 및 이의 신규한 제조방법에 관한 것으로 금속 미네랄원과 단분자 아미노산을 수용액상에서 반응시키고 선택적으로 여과, 농축하고 감압건조 혹은 분무건조(spray-drying) 등 건조하여 부산물이 발생되지 않는 금속 미네랄 디아미네이트를 제조하는 방법에 관한 것이다. 더욱 구체적으로는 수용액에서 금속 미네랄원과 산성 아미노산을 반응시켜 제조하거나, 산성의 수용액 상에서 금속 미네랄원과 아미노산을 반응시켜 제조함으로써, 전기적으로 중성이고 부산물이 없는 금속 미네랄 디아미네이트를 제조하는 방법에 관한 것이다. The present invention relates to a metal mineral dianimate and a novel process for producing the same, wherein a metal mineral source and a mono-molecular amino acid are reacted in an aqueous solution, selectively filtered, concentrated and dried under reduced pressure or spray- The present invention relates to a method for producing a metallic mineral diamine which does not occur. More specifically, the present invention relates to a method for producing a metal mineral dianimide which is electrically neutral and has no byproducts by preparing a metal mineral source and an acidic amino acid by reacting them in an aqueous solution or by reacting a metal mineral source with an amino acid in an acidic aqueous solution .
미네랄은 몸을 구성하는 주요 성분으로서, 세포막의 투과성 조절, 대사작용 등 중요한 생리조절 기능의 역할을 하는 필수 영양물질이다. 그러나 현대인들은 식품에 첨가된 식이로 체내에 필요한 미네랄을 모두 섭취하기 어렵기 때문에 보충제로서 많이 섭취하는 실정이다. 이러한 미네랄 보충제로서 섭취 시 가장 중요한 것은 생체 내 흡수율 및 이용률이며, 미네랄이 소장에서 금속이온으로 흡수 되기 위해서는 단일 물질보다 이온화된 미네랄이 잘 흡수된다. 또한 최근 연구에 따르면 미네랄과 단백질 또는 아미노산으로 결합할 경우, 아미노산의 흡수 경로에 따라 소장으로 흡수되는 것으로 밝혀졌다. 이에 따라 미네랄과 아미노산의 결합에 대한 많은 연구가 진행되고 있는 실정이며, 생체흡수율이 증진된 금속 미네랄 킬레이트 또는 미네랄 디아미네이트가 개발되고 있다.Minerals are the main constituent of the body, and they are essential nutrients that play important physiological control functions such as permeability regulation and metabolism of cell membrane. However, modern people eat a lot of supplements because it is difficult to consume all the necessary minerals in the body by the diet added to the food. As such mineral supplements, the most important thing when ingesting is absorption rate and utilization rate in vivo, and in order for the minerals to be absorbed to the metal ion in the small intestine, ionized minerals are more absorbed than a single substance. Recent studies have also shown that when minerals are bound to proteins or amino acids, they are absorbed into the small intestine by the absorption pathway of amino acids. Accordingly, many studies on the binding of minerals and amino acids have been conducted, and metallic mineral chelates or mineral diaminates having enhanced bioabsorption rates have been developed.
금속 미네랄 디아미네이트는 2분자의 아미노산 단분자와 2가 미네랄이온이 이온 및 배위결합하는 화합물이며, 미네랄 킬레이트는 아미노산 수가 6~10개 정도인 올리고펩티드와 미네랄이온이 이온 및 배위결합을 통해 환상의 구조를 가지며 미네랄을 완전히 감싼 구조를 의미한다. 상기 미네랄 디아미네이트는 미네랄이 1개의 아미노산과 결합한 형태인 단순염보다 강한 결합력을 갖지만, 미네랄 킬레이트과 같이 미네랄을 완전히 포위하는 형태인 킬레이트보다는 약한 결합력을 가지고 있다.The metal mineral diamine is a compound in which two molecules of amino acid monomers and divalent mineral ions are ionically and coordinately bound to each other. The mineral chelate is a compound in which oligopeptides and mineral ions having about 6 to 10 amino acids are ion- And it means a structure that completely encloses minerals. The minerals diaminate has a stronger binding force than a simple salt in which a mineral is combined with a single amino acid but has weaker binding force than a chelate in which the mineral is completely surrounded, such as a mineral chelate.
이러한 결합력의 차이는 미네랄 킬레이트 화합물과 유사한 생체 흡수율을 나타내지만, 생체 이용률에 있어서는 미네랄 킬레이트 화합물보다 미네랄 디아미네이트가 높다. 또한, 미네랄 디아미네이트는 단분자 아미노산을 미네랄 단일 원소에 결합시켰기 때문에 분자크기가 세포막을 투과하기에 용이하며, 장벽을 통해 직접 흡수되므로 생체 내 흡수율와 생체 이용률이 높다. 특히 금속 미네랄 디아미네이트는 이온결합과 배위결합의 이중 결합구조로 소화기관을 거치는 중에 분해가 되지 않고 소장에서 활성 흡수가 일어나며, 무기태와 같은 이온화 과정을 거치지 않고, 위장을 통과하여 소장에서 최대 흡수되며, 전기적으로 중성이고, 분자량이 400이하인 소립자로서 장벽에서 쉽게 흡수되어 생체 이용률이 높다. 뿐만 아니라, 분자량이 400이하이므로 피부를 통한 흡수도 가능하므로 경구제나 주사제 외에도 연고나 화장품 등 피부제품으로의 응용이 용이하다. 즉, 금속 미네랄 디아미네이트는 운반분자로서 아미노산을 사용하여 금속 미네랄을 흡수시키게 되면, 흡수를 위하여 활성부위에 대한 경쟁과 관련된 문제와, 금속 미네랄간의 특수미량요소의 흡수저해를 회피할 수 있는 장점이 있다. 따라서 이러한 금속 미네랄 디아미네이트에 제조방법에 대한 연구가 필요한 실정이다. 기존의 금속 미네랄 디아미네이트의 제조방법은, 염화물 또는 황산염과 같은 수용성의 염의 형태를 갖고 있는 물질을 사용하면, 반응공정을 알칼리 상태로 반응이 원활히 이루어지도록 한다. 그러나 부산물이 금속 미네랄 디아미네이트에 함유 될 수 있으며, 또한 부산물은 금속 미네랄 디아미네이트 제조반응에 간섭을 주거나 흡수에 영향을 줄 수 있다. This difference in binding force shows a bioabsorption rate similar to that of the mineral chelate compound, but the bioavailability is higher than that of the mineral chelate compound. In addition, since mineral diamine binds mono-molecular amino acid to a single element of mineral, its molecular size is easy to permeate through the cell membrane and is directly absorbed through the barrier, so that the bioabsorption and bioavailability are high. In particular, the metal mineral diaminate is a double bond structure of ionic bonding and coordination bonding. It is not decomposed while digestive organs go through, and active absorption occurs in the small intestine. It passes through the stomach and does not go through the same ionization process. Absorbed, electrically neutral, small particle with a molecular weight of 400 or less, easily absorbed from the barrier and high bioavailability. In addition, since the molecular weight is less than 400, absorption through the skin is also possible, so it is easy to apply to skin products such as ointment and cosmetics in addition to oral agents and injections. In other words, when metal minerals are absorbed by using amino acids as transporting molecules, metal minerals diamine has problems related to competition for active sites for absorbing, and advantages of avoiding absorption of special trace elements between metal minerals . Therefore, it is necessary to study the preparation method for such metallic mineral diamines. In the conventional method for producing metallic mineral diamines, when a substance having a water-soluble salt form such as chloride or sulfate is used, the reaction is carried out in an alkaline state. However, byproducts may be contained in the metallic mineral diaminate, and the byproducts may interfere with or affect the absorption of the metallic mineral diaminate.
선행기술 대한민국 등록특허 제10-0481326호 '유기태 킬레이트의 제조방법'을 살펴본 바에 의하면, 청구항 1에 있어서, 1) 아미노산과 배위결합시킬 금속 미네랄을 포함하는 염을 물에 녹인 후 NaOH나 KOH를 사용하여 수산화금속을 석출시키는 단계; 2) 상기 수용액에서 수용성인 K 2SO 4, Na 2SO 4 또는 KCl, NaCl염을 필터프레스로 제거하는 단계; 3) 걸러진 M(OH) 2 (여기서 M은 금속이온임)의 수산화금속을 염산으로 용해시키는 단계; 4) 아미노산을 상기 용액에 완전 용해시켜 혼합하는 단계; 5) 상기 혼합 후, NaOH로 아미노산의 pI값까지 서서히 적정하는 단계; 및 6) 생성된 입자를 여과 건조하는 단계로 구성된 다음 화학식 1의 유기태 킬레이트의 제조 방법으로 기재되어 있다. Prior Art Korean Patent Registration No. 10-0481326 discloses a method for producing an organic chelate according to claim 1, wherein 1) a salt containing a metal mineral to be coordinated with an amino acid is dissolved in water and then NaOH or KOH is used Thereby precipitating a metal hydroxide; 2) removing the water-soluble K 2 SO 4 , Na 2 SO 4 or KCl, NaCl salt in the aqueous solution with a filter press; 3) dissolving the metal hydroxide of filtered M (OH) 2 (wherein M is a metal ion) with hydrochloric acid; 4) completely dissolving and mixing the amino acid in the solution; 5) After the above mixing, slowly titrating to the pI value of the amino acid with NaOH; And 6) filtering and drying the resulting particles.
하기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the following scheme, X is a divalent metal ion and AA is an amino acid.
XCO 3 + 2H(AA) → X(AA) 2 + CO 2 + H 2O XCO 3 + 2H (AA) - > X (AA) 2 + CO 2 + H 2 O
하기 반응식에서, X 는 2가 금속이온이고, M 은 X 이외의 2가 금속이온이며, AA 는 아미노산이다.In the following reaction formula, X is a divalent metal ion, M is a divalent metal ion other than X, and AA is an amino acid.
XCO 3 + 2H(AA) + MSO 4 → M(AA) 2 + CO 2 + H 2O + XSO 4 XCO 3 + 2H (AA) + MSO 4 ? M (AA) 2 + CO 2 + H 2 O + XSO 4
하기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the following scheme, X is a divalent metal ion and AA is an amino acid.
XCO 3 + 2H(AA) → X(AA) 2 + CO 2 + H 2O ------ (1)XCO 3 + 2H (AA) - > X (AA) 2 + CO 2 + H 2 O -
X(AA) 2 + MSO 4 → M(AA) 2 + XSO 4 ----------- (2)X (AA) 2 + MSO 4 ? M (AA) 2 + XSO 4 ????? (2)
따라서 선행 기술에서는 상기 반응식들에서 볼 수 있는 바와 같이, 금속의 탄산염과 아미노산을 반응한 뒤, 금속의 황산염을 이용한 치환반응을 거쳐야 하므로 반응공정이 부산물의 제거공정이 거쳐야 하는 문제가 발생한다. 이에 본 발명자는 부산물이 생성되는 상기 문제점을 극복한 금속 미네랄 디아미네이트를 제조방법을 개발함으로서 본 발명을 완성하였다.Therefore, in the prior art, since the metal carbonate is reacted with the amino acid and then the metal is replaced with the sulfate, as shown in the above reaction schemes, there is a problem that the reaction process requires the removal of by-products. Accordingly, the present inventors have completed the present invention by developing a process for producing metallic mineral diamines that overcomes the above-mentioned problem of by-products.
본 발명은 금속 미네랄 디아미네이트 및 이의 제조방법을 제공하는 것이다. The present invention provides metal mineral diamines and processes for their preparation.
더욱 구체적으로는 수용액에서 금속 미네랄원과 산성 아미노산을 반응시켜 제조하거나 산성의 수용액 상에서 금속 미네랄원과 아미노산을 반응시켜 제조하고, 제조된 용액을 선택적으로 여과, 농축하고 감압건조 혹은 분무건조(spray-drying) 등 건조하여 전기적으로 중성이고 부산물이 없는 금속 미네랄 디아미네이트 및 이를 제조하는 방법을 제공하는 것이다. 또한, 본 발명은 상기 방법에 의해 제조된 금속 미네랄 디아미네이트를 약리학적 유효량, 식품영양학적 유효량 또는 화장학적 유효량으로 함유하고 있는 조성물을 제공하는 것이다. 또한, 본 발명은 우리딘 또는 우리딘 유도체와 금속 미네랄 디아미네이트를 포함하는 화장료 조성물을 제공하는 것이다.More specifically, it is prepared by reacting a metal mineral source with an acidic amino acid in an aqueous solution, or by reacting a metal mineral source with an amino acid in an acidic aqueous solution. The resulting solution is selectively filtered, concentrated and dried under reduced pressure or spray- drying and the like to provide a metal mineral dianimide which is electrically neutral and free from by-products and a method for producing the same. The present invention also provides a composition comprising the metal mineral diaminate prepared by the above method in a pharmacologically effective amount, a nutritionally effective amount or a cosmetically effective amount. The present invention also provides a cosmetic composition comprising a uridine or uridine derivative and a metallic mineral diaminate.
본 발명은 금속 미네랄원과 아미노산을 0.1 내지 70중량%의 농도로 물에 첨가하여 금속 미네랄·단분자 아미노산 수용액을 제조하거나 각각의 수용액을 제조하여 혼합하는 단계; 상기 제조된 금속 미네랄아미노산 수용액을 일정시간 산성의 조건하에서 반응시키는 단계; 선택적으로 반응 수용액을 여과하거나 농축하는 단계; 및 건조하여 분말화하는 단계; 를 포함하는 금속 미네랄 디아미네이트의 제조방법을 과제 해결을 위한 수단으로 제공한다.The present invention relates to a method for producing a metal mineral / mono-molecular amino acid aqueous solution, comprising the steps of: adding a metal mineral source and an amino acid to water at a concentration of 0.1 to 70% by weight; Reacting the prepared metal mineral amino acid aqueous solution under an acidic condition for a predetermined time; Optionally filtering or concentrating the reaction aqueous solution; And drying and pulverizing; And a method for producing the metal mineral diamine.
한 본 발명은 금속 미네랄원과 아미노산을 0.1 내지 70중량%의 농도로 물에 첨가하여 금속 미네랄·단분자 아미노산 수용액을 제조하거나 각각의 수용액을 제조하여 혼합하는 단계; 상기 금속 미네랄·아미노산 수용액을 일정시간 교반하면서 40 내지 100℃로 가온하여 반응하는 단계; 선택적으로 반응 수용액을 여과하거나 농축하는 단계; 및 건조하여 분말화하는 단계; 를 포함하는 금속 미네랄 디아미네이트의 제조방법을 과제 해결을 위한 또 다른 수단으로 제공한다.The present invention relates to a method for producing a metal mineral / mono-molecular amino acid aqueous solution, comprising the steps of: adding a metal mineral source and an amino acid to water at a concentration of 0.1 to 70% by weight; Reacting the aqueous solution of the metal mineral and amino acid by heating at 40 to 100 캜 with stirring for a certain period of time; Optionally filtering or concentrating the reaction aqueous solution; And drying and pulverizing; As a further means for solving the problems.
본 발명은, 상기 금속 미네랄원 용액과 아미노산 용액은 금속 미네랄원의 미네랄과 아미노산의 몰비를 기준으로 1 : 1 내지 4의 비율로 혼합된 것을 특징으로 할 수 있다.In the present invention, the metal mineral source solution and the amino acid solution may be mixed at a ratio of 1: 1 to 4 based on the molar ratio of the mineral and amino acid of the metal mineral source.
본 발명은, 상기 아미노산이 알칼리성 아미노산인 경우, 상기 금속 미네랄·아미노산 수용액의 산도를 완충용액을 사용하여 pH4~8로 조절는 것임을 특징으로 하는 금속 미네랄 디아미네이트의 제조방법을 제공함으로서 기술적 문제를 해결하고자 한다.In the present invention, when the amino acid is an alkaline amino acid, the pH of the metal mineral / amino acid aqueous solution is adjusted to a pH of 4 to 8 by using a buffer solution. I want to.
본 발명은, 상기 금속 미네랄·아미노산 수용액을 감압건조, 동결건조 또는 분무건조(spray-drying)하여 분말화하는 단계를 더욱 포함하는 것을 특징으로 하는 금속 미네랄 디아미네이트의 제조방법을 제공함으로서 기술적 문제를 해결하고자 한다.The present invention further provides a process for producing metallic mineral diamines characterized by further comprising the step of pulverizing the metallic mineral-amino acid aqueous solution by vacuum drying, freeze-drying or spray-drying, .
본 발명은, 상기 금속 아미노산은 산성아미노산인 것을 특징으로 하는 금속 미네랄 디아미네이트의 제조방법을 제공함으로서 기술적 문제를 해결하고자 한다.The present invention provides a method for producing metal mineral diamines, wherein the metal amino acid is an acidic amino acid.
본 발명은, 상기 금속 미네랄원과 아미노산이 각각 1종 이상 포함하는 것을 특징으로 하는 금속 미네랄 디아미네이트의 제조방법을 제공함으로서 기술적 문제를 해결하고자 한다. The present invention provides a method for producing metallic mineral diamines, which comprises at least one metal mineral source and at least one amino acid, respectively, to solve the technical problems.
본 발명은, 금속 미네랄 디아미네이트는 구리 글루타메이트/아스파테이트(cooper glutamate/aspartate), 구리 비스글루타메이트(cooper bisglutamate), 구리 비스아스파테이트(cooper bisaspartate), 아연 글루타메이트/아스파테이트(zinc glutamate/aspartate), 아연 비스글루타메이트(zinc bisglutamate), 아연 비스아스파테이트(zinc bisaspartate), 철 글루타메이트/아스파테이트(iron glutamate/aspartate), 철 비스글루타메이트(iron bisglutamate), 철 비스아스파테이트(iron bisaspartate), 철 비스글루타메이트/아스파테이트(iron bisglutamate/aspartate), 철 글루타메이트/비스아스파테이트(iron glutamate/ bisaspartate), 크롬 글루타메이트/아스파테이트(chromium glutamate/aspartate), 크롬 비스글루타메이트(chromium bisglutamate), 크롬 비스아스파테이트(chromium bisaspartate), 크롬 비스글루타메이트/아스파테이트(chromium bisglutamate/aspartate), 크롬 글루타메이트/비스아스파테이트 (chromium glutamate/ bisaspartate), 코발트 글루타메이트/아스파테이트(covalt glutamate/aspartate), 코발트 비스글루타메이트(covalt bisglutamate), 코발트 비스아스파테이트(covalt bisaspartate), 마그네슘 글루타메이트/스파테이트(magnesium glutamate/aspartate), 마그네슘 비스글루타메이트(magnesium bisglutamate), 마그네슘 비스아스파테이트(magnesium bisaspartate), 망간 글루타메이트/아스파테이트(manganese glutamate/aspartate), 망간 비스글루타메이트(manganese bisglutamate) 또는 망간 비스아스파테이트(manganese bisaspartate)에서 선택된 어느 하나인 것을 특징으로 하는 금속 미네랄 디아미네이트의 제조방법을 제공함으로서 기술적 문제를 해결하고자 한다. The present invention is based on the finding that the metal mineral diaminates are selected from the group consisting of copper glutamate / aspartate, cooper bisglutamate, cooper bisaspartate, zinc glutamate / aspartate, Zinc bisglutamate, zinc bisaspartate, iron glutamate / aspartate, iron bisglutamate, iron bisaspartate, iron bisglutamate, / Iron aspartate, iron glutamate / bisaspartate, chromium glutamate / aspartate, chromium bisglutamate, chromium bisaspartate, ), Chromium bisglutamate / aspartate, aspartate, chromium glutamate / bisaspartate, covalt glutamate / aspartate, covalt bisglutamate, covalt bisaspartate, magnesium glutamate / for example, magnesium glutamate / aspartate, magnesium bisglutamate, magnesium bisaspartate, manganese glutamate / aspartate, manganese bisglutamate or manganese bisaspartate, and bisaspartate. The present invention provides a method for preparing the metal mineral diamine.
본 발명은, 상기 방법으로 제조된 전기적으로 중성인 금속 미네랄 디아미네이트를 제공함으로서 기술적 문제를 해결하고자 한다. The present invention aims to solve the technical problem by providing an electrically neutral metal mineral dianimate produced by the above method.
본 발명은, 상기 금속 미네랄 디아미네이트는 구리 글루타메이트/아스파테이트(cooper glutamate/aspartate), 구리 비스글루타메이트(cooper bisglutamate), 구리 비스아스파테이트(cooper bisaspartate), 아연 글루타메이트/아스파테이트(zinc glutamate/aspartate), 아연 비스글루타메이트(zinc bisglutamate), 아연 비스아스파테이트(zinc bisaspartate), 철 글루타메이트/아스파테이트(iron glutamate/aspartate), 철 비스글루타메이트(iron bisglutamate), 철 비스아스파테이트(iron bisaspartate), 철 비스글루타메이트/아스파테이트(iron bisglutamate/aspartate), 철 글루타메이트/비스아스파테이트(iron glutamate/ bisaspartate), 크롬 글루타메이트/아스파테이트(chromium glutamate/aspartate), 크롬 비스글루타메이트(chromium bisglutamate), 크롬 비스아스파테이트(chromium bisaspartate), 크롬 비스글루타메이트/아스파테이트(chromium bisglutamate/aspartate), 크롬 글루타메이트/비스아스파테이트 (chromium glutamate/ bisaspartate), 코발트 글루타메이트/아스파테이트(covalt glutamate/aspartate), 코발트 비스글루타메이트(covalt bisglutamate), 코발트 비스아스파테이트(covalt bisaspartate), 마그네슘 글루타메이트/아스파테이트(magnesium glutamate/aspartate), 마그네슘 비스글루타메이트(magnesium bisglutamate), 마그네슘 비스아스파테이트(magnesium bisaspartate), 망간 글루타메이트/아스파테이트(manganese glutamate/aspartate), 망간 비스글루타메이트(manganese bisglutamate) 또는 망간 비스아스파테이트(manganese bisaspartate)에서 선택된 어느 하나 인것을 특징으로 하는 금속 미네랄 디아미네이트를 제공함으로서 기술적 문제를 해결하고자 한다.The present invention relates to the above-mentioned metal mineral dianimide, which comprises copper glutamate / aspartate, cooper bisglutamate, cooper bisaspartate, zinc glutamate / aspartate, zinc glutamate / aspartate, ), Zinc bisglutamate, zinc bisaspartate, iron glutamate / aspartate, iron bisglutamate, iron bisaspartate, iron bis The present invention relates to a method for the treatment and / or prophylaxis of an inflammatory disease or condition selected from the group consisting of iron bisglutamate / aspartate, iron glutamate / bisaspartate, chromium glutamate / aspartate, chromium bisglutamate, chromium bisaspartate, bisaspartate, chromium bisglue / aspartate, cobalt bisaspartate, cobalt glutamate / aspartate, cobalt bisglutamate, cobalt bisaspartate, magnesium glutamate / aspartate, chromium glutamate / bisaspartate, But are not limited to, magnesium glutamate / aspartate, magnesium bisglutamate, magnesium bisaspartate, manganese glutamate / aspartate, manganese bisglutamate or manganese bisaspartate and manganese bisaspartate. The present invention is directed to solve the technical problems by providing the metal mineral diamine.
본 발명은, 우리딘 또는 우리딘 유도체와 금속 미네랄 디아미네이트를 포함하는 항염증 의약 조성물을 제공함으로서 기술적 문제를 해결하고자 한다.The present invention aims at solving the technical problems by providing an antiinflammatory pharmaceutical composition comprising a uridine or uridine derivative and a metal mineral diamine.
본 발명은, 우리딘 또는 우리딘 유도체와 금속 미네랄 디아미네이트를 포함하는 화장료 조성물을 제공함으로서 기술적 문제를 해결하고자 한다.The present invention aims at solving technical problems by providing a cosmetic composition comprising a uridine or uridine derivative and a metallic mineral diaminate.
본 발명은 신규한 금속 미네랄 디아미네이트의 제조방법에 관한 것으로, 더욱 상세하게는 수용액에서 금속 미네랄원과 산성 아미노산을 반응시켜 제조하거나 산성의 수용액 상에서 금속 미네랄원과 아미노산을 반응시켜 제조하고, 제조된 용액을 감압건조, 동결건조 또는 분무건조(spray-drying)하여 전기적으로 중성이고 부산물이 없는 금속 미네랄 디아미네이트를 제조하는 방법을 제공할 수 있다. 본 발명은 상기 방법에 의해 제조된 금속 미네랄 디아미네이트는 온도 및 pH에서 안정성을 유지하고, 제품의 물성과 맛에 영향을 미치지 않으며, 높은 체내 흡수율을 나타내므로, 의약품, 음료, 화장품, 일반식품, 사료, 식물성장 촉진제로서 널리 활용될 수 있다.More particularly, the present invention relates to a process for producing a novel metal mineral dianimate by reacting a metal mineral source with an acidic amino acid in an aqueous solution or by reacting a metal mineral source with an amino acid in an acidic aqueous solution, Dried, freeze-dried or spray-dried to produce a metal-mineral dianimide which is electrically neutral and free of byproducts. The present invention relates to a metal mineral dianimate produced by the above method, which maintains stability at a temperature and a pH, does not affect the physical properties and taste of the product, exhibits a high absorption rate in the body, , Feed, and plant growth promoters.
도 1은 금속 미네랄 디아미네이트의 결합 및 구조식을 나타낸 도면이다. 도 2는 분무건조를 이용하여 제조한 아연 아스파르트산 디아미네이트의 사진이다. 도 3은 분무건조를 이용하여 제조한 망간 아스파르트산 디아미네이트의 사진이다. 도 4는 분무건조를 이용하여 제조한 칼슘 글루탐산 디아미네이트의 사진이다. 도 5는 아연 아스파테이트 디아미네이트가 리포폴리사카라이드가 처리된 RAW 264.7 세포의 산화질소 생성에 미치는 효과를 나타낸 도면이다.BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a view showing the bonding and structural formula of a metallic mineral diaminate. FIG. 2 is a photograph of a zinc aspartate diaminate prepared by spray drying. Figure 3 is a photograph of manganese aspartic acid diaminate prepared by spray drying. 4 is a photograph of calcium glutamic acid diaminate prepared by spray drying. Figure 5 shows the effect of zinc aspartate diaminate on the production of nitric oxide of RAW 264.7 cells treated with lipopolysaccharide.
본 명세서 및 청구범위에 사용된 용어나 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 안되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다. 따라서 본 명세서에 기재된 제조예, 실험예, 실시예 및 도면에 기술된 사항은 본 발명의 가장 바람직한 일 예에 불과할 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다.The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary meanings and the inventor can properly define the concept of the term to describe its invention in the best possible way And should be construed in accordance with the principles and meanings and concepts consistent with the technical idea of the present invention. Therefore, the manufacturing examples, the experimental examples, the examples, and the drawings described in the present specification are merely the most preferred examples of the present invention and do not represent all the technical ideas of the present invention. Therefore, It should be understood that various equivalents and modifications may be made.
실시예 1. 분무건조 방법으로 금속 미네랄 디아미네이트 제조EXAMPLE 1 Preparation of metallic mineral diaminate by spray drying
금속 미네랄원과 아미노산을 0.1 내지 70중량%의 농도로 용매 물에 첨가하여 금속 미네랄 수용액 및 아미노산 수용액을 각각 제조하여 혼합하거나 또는 혼합하여 수용액을 제조하는 단계; 상기 각 금속 미네랄 수용액 및 아미노산 수용액을 혼합하여 제조한 수용액 또는 각각 제조한 수용액을 혼합한 수용액을 여과하여 금속 미네랄·아미노산 수용액을 제조하는 단계; 상기 금속 미네랄·아미노산 수용액을 필요에 따라 교반하면서 40 내지 100℃로 가온하여 반응하는 단계; 및 금속 미네랄·아미노산 수용액을 분무건조하여 분말화 하는 단계를 포함하는 금속 미네랄 디아미네이트의 제조방법으로 제조한다.Adding a metal mineral source and an amino acid in a concentration of 0.1 to 70% by weight to a solvent to prepare an aqueous solution of a metal mineral and an aqueous solution of an amino acid, respectively, and mixing or mixing them to prepare an aqueous solution; Preparing an aqueous metal mineral / amino acid solution by filtering an aqueous solution prepared by mixing each aqueous solution of metal mineral and an aqueous solution of amino acid or an aqueous solution obtained by mixing the prepared aqueous solution; Reacting the metal mineral-amino acid aqueous solution with heating at 40 to 100 ° C while stirring as required; And a step of spray-drying and pulverizing a metal mineral / amino acid aqueous solution.
상기 금속 미네랄원의 미네랄과 아미노산의 몰비를 1:1 ~ 4로 혼합하며, 용매로는 바람직하게 물이 사용될 수 있지만, 기타 반응물에 영향을 미치지 않으면서 반응 후 용이하게 제거될 수 있는 것이라면 특별히 제한되는 것은 아니다. 용매는 물, 알칼리성 용매, 산성용매 또는 유기용매를 사용할 수 있다. 또한, 수용액에서 공정의 효율성을 높이기 위하여 중성 또는 알카리성의 아미노산을 사용하는 경우, 산성의 수용액조건을 충족하기 위하여 완충액 용액을 첨가할 수 있다. pH는 원활한 반응성과 생성물의 중성을 유지하기 위하여, pH 4 내지 8로 조절하는 것이 바람직하며, 더욱 바람직한 반응 pH 는 5 내지 7.5 이다. 반응온도는 0 내지 100℃인 것이 바람직하며, 온도가 너무 낮으면 반응성이 떨어지고, 반면에 온도가 너무 높으면 과도한 에너지 사용의 문제점과 일부 아미노산이 변질된 가능성이 있으므로 바람직하지 않다.The molar ratio of the minerals to the amino acids in the metal mineral source is 1: 1 to 4, and as the solvent, water can be preferably used. However, if it can be easily removed after the reaction without affecting other reactants, It is not. The solvent may be water, an alkaline solvent, an acidic solvent or an organic solvent. Further, in the case of using a neutral or alkaline amino acid in order to increase the efficiency of the process in an aqueous solution, a buffer solution may be added to satisfy an acidic aqueous solution condition. The pH is preferably adjusted to a pH of from 4 to 8, more preferably from 5 to 7.5, in order to maintain smooth reactivity and neutrality of the product. The reaction temperature is preferably from 0 to 100 ° C, and if the temperature is too low, the reactivity is deteriorated. On the other hand, if the temperature is too high, there is a problem of excessive energy use and a possibility that some amino acids are altered.
1) 금속 미네랄원과 아미노산1) Metal Mineral Resources and Amino Acids
본 발명에 사용될 수 있는 금속 미네랄원은 특별히 제한되는 것은 아니며, 예를 들어, 칼슘, 구리, 아연, 철, 크롬, 코발트, 망간, 마그네슘, 셀레늄 등의 2가 또는 그 이상의 원자가를 가진 금속들의 염을 포함하며, 경우에 따라서는, 이들의 둘 또는 그 이상의 혼합물이 사용될 수도 있다. 상기 금속 미네랄원의 구체적인 예로는, 황산동, 글구콘산동, 산화마그네슘, 젖산마그네슘, 탄산마그네슘, 황산마그네슘, 글로콘산마그네슘, 염화마그네슘, 황산망간, 염화망간, 산화아연, 황산아연, 글루콘산아연, 구연산철, 젖산철, 황산제일철, 푸마르산제일철, 인산철, 산화칼슘, 젖산칼슘, 탄산칼슘, 구연산칼슘, 제이인산칼슘, 수산화칼슘, 제삼인산칼슘, 글루콘산칼슘, 염화크롬을 들 수 있다. 본 발명의 금속 미네랄원은 자연계에 존재하는 천연이거나, 인위적으로 합성한 비천연의 금속 미네랄원이거나, 그것이 의약원료, 식품원료, 화장품원료이거나 또는 공업용원료인 경우에도 무방하며, 경우에 따라서는 이들의 둘 또는 그 이상의 혼합 형태로 사용될 수도 있다. 본 발명에 사용될 수 있는 아미노산은 특별히 한정되는 것은 아니나, 산성의 반응조건을 충족하기 위하여 아미노산은 예를 들어, 글루타민산, 아스파르트산이 바람직하며, 경우에 따라서는 이들의 둘 또는 그 이상의 혼합 형태로 사용될 수도 있다. 아미노산이 글루타민산과 아스파르트산과 같은 산성아미노산이 아닌 경우에는 산성의 수용액을 사용하는 것이 바람직하다. 또한, 경우에 따라서 원활한 디아미네이트의 제조를 위하여 가온공정이 필요로 될 수 있다.The metal mineral source that can be used in the present invention is not particularly limited and includes salts of metals having a valence of 2 or more such as calcium, copper, zinc, iron, chromium, cobalt, manganese, magnesium, selenium, , And in some cases, a mixture of two or more thereof may be used. Specific examples of the metallic mineral source include copper sulfate, magnesium carbonate, magnesium lactate, magnesium carbonate, magnesium sulfate, magnesium gluconate, magnesium chloride, manganese sulfate, manganese chloride, zinc oxide, zinc sulfate, zinc gluconate, Calcium ferric oxide, calcium ferric oxide, calcium lactate, calcium carbonate, calcium citrate, calcium phosphate dibasic, calcium hydroxide, tribasic calcium phosphate, calcium gluconate, and chromium chloride. The metal mineral source of the present invention may be a natural or artificially synthesized non-natural metal mineral resource present in nature, or it may be a pharmaceutical raw material, a food raw material, a cosmetic raw material, or an industrial raw material, Or a mixture of two or more thereof. The amino acid which can be used in the present invention is not particularly limited, but in order to satisfy the acidic reaction condition, the amino acid is preferably, for example, glutamic acid or aspartic acid, and may be used in a mixture form of two or more thereof have. When the amino acid is not an acidic amino acid such as glutamic acid and aspartic acid, it is preferable to use an acidic aqueous solution. In some cases, a heating process may be required for the production of smooth diaminates.
2) 금속 미네랄원과 아미노산의 반응 2) Reaction of metal mineral source with amino acid
본 발명의 금속 미네랄원과 아미노산을 이용한 디아미네이트 반응은 하기 반응식 1과 같이 표현될 수 있다.The diamination reaction using the metal mineral source and the amino acid of the present invention can be expressed as shown in the following reaction formula (1).
반응식 1 (산화금속 미네랄인 경우)Scheme 1 (for metal oxide minerals)
XO + 2H(AA) → X(AA) 2 + H 2OXO + 2H (AA) → X (AA) 2 + H 2 O
상기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the above reaction formula, X is a divalent metal ion, and AA is an amino acid.
반응식 2 (젖산금속 미네랄인 경우)Reaction formula 2 (in the case of lactic acid metal mineral)
X·+ 2H(AA) → X(AA) 2 + 2 lactic acidX + 2H (AA) - > X (AA) 2 + 2 lactic acid
상기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the above reaction formula, X is a divalent metal ion, and AA is an amino acid.
반응식 3 (구연산금속 미네랄인 경우)Reaction 3 (in the case of metal citrate minerals)
X·+ 2H(AA) → X(AA) 2 + 2 citric acidX + 2H (AA) - > X (AA) 2 + 2 citric acid
상기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the above reaction formula, X is a divalent metal ion, and AA is an amino acid.
반응식 4 (글루콘산금속 미네랄인 경우)Reaction formula 4 (in the case of metal gluconate mineral)
X·+ 2H(AA) → X(AA) 2 + 2 gluconic acidX + 2H (AA) - > X (AA) 2 + 2 gluconic acid
상기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the above reaction formula, X is a divalent metal ion, and AA is an amino acid.
반응식 5 (염화금속 미네랄인 경우)Scheme 5 (in the case of metal chloride minerals)
X·+ 2H(AA) → X(AA) 2 + 2 HClX + 2H (AA) - > X (AA) 2 + 2 HCl
상기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the above reaction formula, X is a divalent metal ion, and AA is an amino acid.
반응식 7 (황산금속 미네랄인 경우)Scheme 7 (in the case of metal sulfate minerals)
X·+ 2H(AA) → X(AA) 2 + H 2SO 4 X · + 2H (AA) → X (AA) 2 + H 2 SO 4
상기 반응식에서, X 는 2가 금속이온이고, AA 는 아미노산이다.In the above reaction formula, X is a divalent metal ion, and AA is an amino acid.
상기 반응식들에서 볼 수 있는 바와 같이, 본 발명에 따른 방법으로 금속 미네랄 디아미네이트를 제조하면, 황산나트륨을 포함한 부반응물이 발생하지 않으며, 부산물 또한 각각 휘발되거나 그 자체로서 생성물에 영향을 끼치지 않으므로 생성물의 분리가 용이하고, 전기적으로 중성 형태의 금속 미네랄 디아미네이트가 제조될 수 있다. 무엇보다 매개 또는 치환공정이 전혀 없으며, 단일 반응만으로 제조할 수 있어 경제적으로 매우 효과적인 장점이 있다. 즉, 본 발명은 상기방법으로 제조된 하기 화학식 1 또는 화학식 2로서 표시되는 금속 미네랄 디아미네이트에 관한 것이다.As can be seen from the above reaction schemes, when the metal mineral diamine is prepared by the process according to the present invention, no byproducts including sodium sulfate are produced, and the by-products also do not volatilize or affect the products as such The separation of the product is easy, and an electrically neutral metal mineral diamine can be produced. Above all, there is no mediation or substitution process, and it is possible to manufacture by only a single reaction, which is economically very effective. That is, the present invention relates to a metal mineral diamine represented by the following formula (1) or (2) prepared by the above method.
화학식 1Formula 1
M(AA) 2M (AA) 2
상기 식에서, M 은 2가 금속이온이고, AA 는 아미노산이다.Wherein M is a divalent metal ion and AA is an amino acid.
상기 화학식 1의 구조식을 도 1에 도시하였다.The structural formula of the above formula (1) is shown in Fig.
화학식 2(2)
M'(AA) 3M '(AA) 3
상기 식에서 M' 는 3가 금속이온이고, AA 는 아미노산이다.Wherein M 'is a trivalent metal ion and AA is an amino acid.
3) 분무건조 3) Spray drying
분무건조(Spray drying) 기술은 액상, 유기용액, 에멀젼, 분산액(dispersion) 또는 현탁액(suspension)과 같은 액상시료를 분무, 미립화하여서 열풍기류 속에 접촉시키면 증발후 건조되어서 분말화 된다. 분무건조장치(Spray dryer)는 액상 시료를 분무하여, 미세한 droplet 형태로 만든 후, 뜨거운 건조 가스를 이용하여 물(수분)이나 유기용매를 증발시켜서 분말을 제조하는 장치이다. 분무건조(Spray drying)는 액상의 건조 분말화 단일 단계에서 이루어지며, 비용 절감, 손쉬운 Scale-up, 처리 공정의 단순화와 같은 이점을 가지고 있다. 더불어, 효소(enzyme), 단백질 또는 항생물질(antibiotic)과 같이 온도에 민감한 물질은 분무건조(Spray drying) 기술을 사용하여, 열적 변형이 없이 분말화가 가능하기 때문에, 본 발명에서는 상기 미네랄원 용액과 아미노산 용액을 분말건조를 통해 미네랄 킬레이트 제조 및 분말화 하였다. Spray drying technology is a process in which a liquid sample such as a liquid, an organic solution, an emulsion, a dispersion or a suspension is sprayed, atomized, and brought into contact with a hot air stream. The spray dryer is a device for spraying a liquid sample into a fine droplet form, and then evaporating water (water) or an organic solvent using a hot dry gas to produce a powder. Spray drying takes place in a single step of liquid phase drying and has advantages such as cost reduction, easy scale-up, and simplification of processing process. In addition, since temperature-sensitive materials such as enzymes, proteins, or antibiotics can be pulverized without thermal deformation by using a spray drying technique, in the present invention, The amino acid solution was prepared by powder drying and mineral chelate formation.
① 시료 ① Sample
시료 용액은 반드시 펌프로 이송이 가능하여야 하며, 균일하여야 하며 불순물이 없는 수용액, 에멀젼, 현탁액(suspension) 또는 유기용액이어야 한다. 또한, 시료 용액의 전처리는 최종 분무 생성물의 입자 크기, 형태, 입자 코팅에 많은 영향을 미치게 된다. 윤활제(lubricant), 해교제(defloccant) 또는 다른 특별한 물질과 같은 첨가제는 매우 작은 양을 시료용액에 배합해야 한다. 본 발명에서는 각 금속 미네랄 수용액과 아미노산 수용액을 교반하여 제조한 금속 미네랄·아미노산 수용액을 시료로 사용하였다. The sample solution must be pumpable, uniform, and free from impurities such as aqueous solutions, emulsions, suspensions or organic solutions. In addition, pretreatment of the sample solution will greatly affect the particle size, shape and particle coating of the final spray product. Additives such as lubricants, defloccants or other special substances must be incorporated into the sample solution in very small amounts. In the present invention, a metal mineral / amino acid aqueous solution prepared by stirring each metal mineral aqueous solution and an amino acid aqueous solution was used as a sample.
② 분무 / 건조 가스 접촉② Spray / dry gas contact
시료 용액을 분주하여 보다 미세한 물방울(droplet)을 얻기 위해서 다양한 방식의 nozzle을 사용한다. 일반적으로 사용되는 노즐(nozzle)의 형태는 이중 노즐(two fluid nozzle), 압력 노즐(pressure nozzle), 회전 디스크 애토마이저(rotary disk atomizer) 또는 초음파 노즐(ultrasonic nozzle)이 있다. 주입구(inlet) 온도(건조 가스의 온도)는 50~550℃로 분무건조 가능하며 바람직하게는 50~150℃의 온도로 금속 미네랄·아미노산 수용액을 분무 건조한다. 분주 장치의 선택은 처리하고자 하는 시료 용액의 양과 특성 그리고 만들고자 하는 분무 건조물의 특성을 고려한다. 본 발명에서는 최종 산물인 미네랄 디아미네이트의 입자크기에 따라 노즐을 선택하여 제조한다. A variety of nozzles are used to dispense the sample solution to obtain finer droplets. A commonly used type of nozzle is a two fluid nozzle, a pressure nozzle, a rotary disk atomizer, or an ultrasonic nozzle. The inlet temperature (the temperature of the drying gas) can be spray dried at a temperature of 50 to 550 ° C., and a metal mineral / amino acid aqueous solution is spray dried at a temperature of preferably 50 to 150 ° C. The selection of the dispensing device takes into account the amount and nature of the sample solution to be treated and the nature of the spray dryer desired to be made. In the present invention, the nozzle is selected according to the particle size of the mineral diamine, which is the final product.
③ 증발(evaporation), 입자 형태 생성 및 건조③ evaporation, formation of particles and drying
분사 장치에서 분사된 시료 용액은 droplet을 생성하고, 이 droplet가 뜨거운 건조 공기와 접촉하자 마자 droplet 표면에 포화된 기화 가스가 얇은 막을 형성한다. 이 얇은 막에서 증발(evaporation)이 발생한다. 높은 비표면적, 적정 온도, 열에 의한 수분 변화율, 질량 변화에 따라서 효과적인 건조가 가능하며, 증발(evaporation)은 가스의 온도를 떨어뜨리며, 최종 생산물의 열에 의한 피해를 최소화한다. 본 발명에서는 금속 미네랄 수용액과 아미노산 수용액을 교반하여 제조한 금속 미네랄·아미노산 수용액을 상기 분무건조장치를 이용하여 분말화 함으로써, 금속 미네랄 디아미네이트를 제조하였다.The sample solution injected from the injector generates droplets, and as soon as the droplets come into contact with hot dry air, the vaporized gas saturated on the droplet surface forms a thin film. Evaporation occurs in this thin film. Effective drying is possible according to the high specific surface area, the optimum temperature, the rate of moisture change by heat, the mass change, and the evaporation lowers the temperature of the gas and minimizes the heat damage of the final product. In the present invention, a metallic mineral / amino acid aqueous solution prepared by stirring a metallic mineral aqueous solution and an amino acid aqueous solution is pulverized using the above-described spray drying apparatus to prepare a metallic mineral diaminate.
4) 제조된 금속 미네랄 킬레이트 4) The produced metal mineral chelate
본 발명의 반응을 통해 제조될 수 있는 대표적인 아미노산 금속 미네랄디아미네이트의 종류를 보면 다음과 같지만, 이로 제한되는 것은 아니다. 상기 제시된 방법으로 제조한 금속 미네랄 킬레이트는 칼슘 글루타메이트/아스파테이트 (calcium glutamate/aspartate), 칼슘 글루타메이트/메치오닌(calcium glutamate/methionine), 칼슘 글루타메이트/글리신(calcium glutamate/glycine), 칼슘 아스파테이트/메치오닌(calcium aspartate/methionine), 칼슘 아스파테이트/글리신(calcium aspartate/glycine), 칼슘 메치오닌/글리신(calcium methionine/glycine), 칼슘 비스글루타메이트(calcium bisglutamate), 칼슘 비스아스파테이트(calcium bisaspartate), 칼슘 비스메치오닌 (calcium bismethionine) 또는 칼슘 비스글리신(calcium bisglycine)으로 제조되며, 또한, 이들을 하나 이상 조합하여 새로운 금속 미네랄 디아미네이트 혼합물을 제조할 수 있다. 또한, 구리 글루타메이트/아스파테이트(cooper glutamate/aspartate), 구리 비스글루타메이트(cooper bisglutamate), 구리 비스아스파테이트(cooper bisaspartate), 아연 글루타메이트/아스파테이트(zinc glutamate/aspartate), 아연 비스글루타메이트(zinc bisglutamate), 아연 비스아스파테이트(zinc bisaspartate), 철 글루타메이트/아스파테이트(iron glutamate/aspartate), 철 비스글루타메이트(iron bisglutamate), 철 비스아스파테이트(iron bisaspartate), 철 비스글루타메이트/아스파테이트(iron bisglutamate/aspartate), 철 글루타메이트/비스아스파테이트(iron glutamate/ bisaspartate), 크롬 글루타메이트/아스파테이트(chromium glutamate/aspartate), 크롬 비스글루타메이트(chromium bisglutamate), 크롬 비스아스파테이트(chromium bisaspartate), 크롬 비스글루타메이트/아스파테이트(chromium bisglutamate/aspartate), 크롬 글루타메이트/비스아스파테이트(chromium glutamate/ bisaspartate), 코발트 글루타메이트/아스파테이트(covalt glutamate/aspartate), 코발트 비스글루타메이트(covalt bisglutamate), 코발트 비스아스파테이트(covalt bisaspartate), 마그네슘 글루타메이트/아스파테이트(magnesium glutamate/aspartate), 마그네슘 비스글루타메이트(magnesium bisglutamate), 마그네슘 비스아스파테이트(magnesium bisaspartate), 망간 글루타메이트/아스파테이트(manganese glutamate/aspartate), 망간 비스글루타메이트(manganese bisglutamate) 또는 망간 비스아스파테이트(manganese bisaspartate)으로 제조되며, 또한, 이들을 하나 이상 조합하여 새로운 금속 미네랄 디아미네이트 혼합물을 제조할 수 있다.Representative amino acid metal mineral diamines that can be prepared through the reaction of the present invention include, but are not limited to, the following. The metal mineral chelate produced by the method described above may be selected from the group consisting of calcium glutamate / aspartate, calcium glutamate / methionine, calcium glutamate / glycine, calcium aspartate / methionine calcium aspartate / methionine, calcium aspartate / glycine, calcium methionine / glycine, calcium bisglutamate, calcium bisaspartate, calcium bis-methionine calcium bismethionine or calcium bisglycine, and furthermore, one or more of these may be combined to produce a new metal mineral diaminate mixture. It is also possible to use copper glutamate / aspartate, cooper bisglutamate, cooper bisaspartate, zinc glutamate / aspartate, zinc bisglutamate, Zinc bisaspartate, iron glutamate / aspartate, iron bisglutamate, iron bisaspartate, iron bisglutamate / aspartate, ), Iron glutamate / bisaspartate, chromium glutamate / aspartate, chromium bisglutamate, chromium bisaspartate, chromium bis glutamate / aspartate, (chromium bisglutamate / aspartate), chromium glutamate / bisla Cobalt glutamate / aspartate, covalt bisglutamate, covalt bisaspartate, magnesium glutamate / aspartate, cobalt glutamate / aspartate, cobalt glutamate / aspartate, Magnesium bisglutamate, magnesium bisaspartate, manganese glutamate / aspartate, manganese bisglutamate or manganese bisaspartate, and is also prepared from magnesium bisaspartate, , One or more of which may be combined to produce a new metal mineral dianemate mixture.
5) 금속 미네랄 디아미네이트 분석5) Analysis of metallic mineral diaminate
상기 금속 미네랄 디아미네이트는 ① FT-IR 적외선분광법(금속 미네랄 디아미네이트 구조), ③ ICP발광분석법(원소 함량측정), ③아미노산분석법(아미노산 함량측정)의 방법으로 금속 미네랄 디아미네이트를 분석하였다.  The metal mineral diaminate is analyzed by the method of ① FT-IR infrared spectroscopy (metal mineral diamine structure), ③ ICP emission spectrometry (element content measurement), and ③ amino acid analysis (amino acid content measurement) Respectively.
실시예2. 금속 미네랄 디아미네이트의 안정성 실험Example 2. Stability test of metallic mineral diaminate
실시예 1에서 얻어진 금속 미네랄 디아미네이트 화합물에 대해 수용액상에서의 장기보존에 따른 안전성 실험을 행하였다. The metal mineral diaminate compound obtained in Example 1 was subjected to a safety test according to long-term preservation in an aqueous solution.
실험조건 : 1) 증류수의 pH를 각각 3, 5, 7, 및 9로 조절하고 상기 화합물을 첨가한 시료, 2) 완충액을 사용하여 pH를 각각 3, 5, 7, 및 9로 조절하고 상기 화합물을 첨가한 시료, 3) 시판되고 있는 음료(비타500, 박카스, 오렌지쥬스)에 상기 화합물을 첨가한 시료, 4) 시판되고 있는 화장품 중 스킨로션에 상기 화합물을 첨가한 시료, 5) 시판되고 있는 식물생장촉진제에 상기 화합물을 첨가한 시료.Experimental conditions were as follows: 1) the pH of the distilled water was adjusted to 3, 5, 7, and 9, the sample was added with the compound, and 2) the pH was adjusted to 3, 5, 7, A sample to which the above compound is added in a commercially available beverage (Vita 500, Bacchus, or Orange juice), 4) a sample in which the compound is added to skin lotion in commercially available cosmetics, 5) A sample in which the compound is added to a plant growth promoter.
이들 시료를 4, 25 및 50℃에 각각 보관한 후, 침전 및 pH의 변화를 측정하였다. 상기의 실험 조건에서 안정성을 3 개월 동안 확인한 결과, 침전 현상이나 유의적인 pH의 변화가 없었다. 따라서, 본 발명에 의하여 제조된 아미노산 금속 미네랄디아미네이트가 수용액상에서 다양한 pH와 온도의 조건에서 매우 안정한 화합물임을 입증되었다.These samples were stored at 4, 25 and 50 ° C, respectively, and the changes of the precipitation and pH were measured. As a result of confirming the stability for 3 months under the above experimental conditions, there was no precipitation phenomenon or significant pH change. Thus, it has been demonstrated that the amino acid metal mineral diamines prepared by the present invention are very stable compounds in aqueous solution at various pH and temperature conditions.
실시예3. 금속 미네랄 디아미네이트를 함유한 조성물 제조 Example 3. Preparation of Composition Containing Metal Mineral Diaminate
본 발명은 상기 화학식 1 또는 2 의 아미노산 디아미네이트를 약제학적 또는 식품영양학적 또는 화장학적 유효량으로 함유하는 조성물에 관한 것이다.The present invention relates to a composition containing the amino acid diaminate of the above formula (1) or (2) in a pharmaceutical or nutritional or cosmetically effective amount.
1) 약학적 제제 1) Pharmaceutical preparations
화학식 1 또는 2의 금속 미네랄 디아미네이트는 목적하는 바에 따라 다양한 약제학적 투여 형태로 제형화될 수 있다. 본 발명에 따른 약제학적 조성물을 제조함에 있어서, 화학식 1 또는 2의 디아미네이트를 제조하고자 하는 제형에 따라 선택될 수 있는 다양한 약제학적으로 허용되는 담체와 함께 혼합하여 사용할 수 있다. 예를 들어, 본 발명에 따른 약제 조성물은 목적하는 바에 따라 주사용 제제, 경구용 제제로 제형화될 수 있다. 활성성분으로서 화학식 1 또는 2의 금속 미네랄 디아미네이트는 공지된 제약용 담체와 부형제를 이용하는 공지의 방법으로 제제화되어 단위 용량 형태 또는 다용량 용기에 내입될 수 있다. 제제 형태는 오일 또는 수성 매질 중의 용액, 현탁액 또는 유화액 형태일 수 있으며, 통상의 분산제, 현탁제 또는 안정화제를 함유할 수 있다. 또한, 예를 들어, 무균, 발열물질이 제거된 물로 사용 전에 녹여 사용하는 건조 분말의 형태일 수도 있다. 화학식 1 또는 2의 금속 미네랄 디아미네이트는, 또한, 코아버터 또는 기타 글리세리드와 같은 통상의 좌약기제를 이용하여 좌약으로 제제될 수도 있다. 경구 투여용 고체투여 형태는 캅셀제, 정제, 환제, 산제 및 입제가 가능하고, 특히 캅셀제와 정제가 유용하다. 정제 및 환제는 장피제로 제조하는 것이 바람직하다. 고체투여 형태에는 활성성분인 화학식 1 또는 2의 금속 미네랄 디아미네이트는 슈크로오즈, 락토오즈, 전분 등과 같은 하나 이상의 불활성 희석제 및 마그네슘 스테아레이트와 같은 윤활제, 붕해제, 결합제등과 같은 딤체와 혼합시킴으로써 제조할 수 있다. 필요한 경우, 본 발명에 따른 화학식 1 또는 2의 금속 미네랄 디아미네이트 또는 그것을 함유하는 조성물은, 기타의 약제와 조합하여 투여할 수도 있다. 상기 약리학적 유효량(therapeutically effective amount)이란, 치료를 요하는 질병의 증상을 경감 또는 줄이거나 예방을 요하는 질병의 임상학적 마커 또는 증상의 개시를 줄이거나 지연시키는데 유효한 활성성분의 량을 의미한다. 약리학적 유효량은 치료를 요하는 질병에 대한 공지된 생체내( in vivo) 및 생체외( in vitro) 모델 시스템에서 화합물을 실험함으로써 경험적으로 결정될 수 있다. 단위 용량 형태로 제형화하는 경우, 활성성분으로서 화학식 1 또는 2의 금속 미네랄 디아미네이트는 약 0.1 내지 1000 ㎎의 단위 용량으로 함유되는 것이 바람직하다. 투여량은 환자의 체중, 나이 및 질병의 특수한 성질과 심각성과 같은 요인에 따라 의사의 처방에 따른다. 그러나, 성인 치료에 필요한 투여량은 투여의 빈도와 강도에 따라 하루에 약 1 내지 1000 ㎎ 범위 가 보통이다. 성인에게 근육내 또는 정맥내 투여시 일회 투여량으로 분리하여 하루에 보통 약 1 내지 500 ㎎의 전체 투여량 이면 충분할 것이나, 일부 환자의 경우 더 높은 일일 투여량이 바람직할 수 있다.The metal mineral diaminates of formula (I) or (II) may be formulated into various pharmaceutical dosage forms as desired. In preparing the pharmaceutical compositions according to the present invention, the diaminates of formula (I) or (II) may be mixed with various pharmaceutically acceptable carriers which may be selected according to the formulations to be prepared. For example, the pharmaceutical composition according to the present invention can be formulated into injectable or oral formulations as desired. The metal mineral diaminates of formula (I) or (II) as active ingredients can be formulated in a known manner using known pharmaceutical carriers and excipients and incorporated into unit dose forms or multi-dose containers. The formulation form may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, and may contain conventional dispersing agents, suspending agents or stabilizing agents. It may also be in the form of a dry powder, for example, dissolved in sterile, pyrogen-free water before use. The metal mineral diaminates of formula (I) or (II) may also be formulated as suppositories using conventional suppository bases such as corn butter or other glycerides. Solid dosage forms for oral administration may be capsules, tablets, pills, powders, and granules, with capsule and tablet being particularly useful. Tablets and pills are preferably prepared as preservative. In the solid dosage form, the active ingredient metal mineral diaminate of formula (I) or (II) is mixed with one or more inert diluents such as sucrose, lactose, starch and the like, and a lubricant such as magnesium stearate, disintegrants, . If necessary, the metal mineral diamine of formula (I) or (II) according to the present invention or the composition containing it may be administered in combination with other medicaments. The therapeutically effective amount means the amount of active ingredient effective to reduce or delay the onset of a clinical marker or symptom of a disease that alleviates, reduces or prevents symptoms of the disease requiring treatment. A pharmacologically effective amount can be determined empirically by testing compounds in known in vivo and in vitro model systems for diseases in need of treatment. When formulated in unit dose form, the metal mineral diamine of formula (I) or (II) as the active ingredient is preferably contained in a unit dose of about 0.1 to 1000 mg. The dosage depends on the physician's prescription depending on factors such as the patient's weight, age and the particular nature and severity of the disease. However, the dosage required for adult therapy is usually in the range of about 1 to 1000 mg per day, depending on the frequency and intensity of administration. A total dosage of about 1 to 500 mg per day, separated by a single dose at the time of intramuscular or intravenous administration to an adult would suffice, but in some patients a higher daily dose may be desirable.
2) 식품영학적 유효량2) food spiritual effective amount
상기 식품영양학적 유효량(sitologically effective amount)이란, 질병에 이르는 정도는 아니지만 객체의 영양 신진대사를 보충하는데 유효하면서, 동시에 과량 투여에 따른 부작용을 유발하지 않는 활성성분의 량을 의미한다.The term " cytologically effective amount " means an amount of the active ingredient that is effective for supplementing the nutritional metabolism of an object, which does not lead to disease, but which does not cause side effects due to overdosage.
3) 화장학적 유효량3) Cosmetically effective amount
상기 화장학적 유효량(cosmetically effective amount)이란, 피부의 건강상태 및 모발의 건강상태 등 객체의 미용과 관련된 영양 상태를 향상시키는데 유효하면서, 동시에 과량 투여에 따른 부작용을 유발하지 않는 활성성분의 양을 의미한다. 상기 식품영양학적 유효량과 화장학적 유효량은 사용될 조성물의 용도 및 성상 등 다양한 요인들에 의해 가변적으로 결정될수 있으므로, 유효량을 특별히 한정지을 필요는 없다. 따라서, 본 발명에 따른 조성물에는 그것의 용도에 따라, 예를 들어, 약학적으로 허용되는 담체를 포함하는 약제 조성물, 식품영양학적으로 허용되는 담체를 포함하는 식품, 사료첨가제 또는 음료 조성물, 화장학적으로 허용되는 담체를 포함하는 화장품 조성물 등 다양한 용도로 응용되어 사용될 수 있다. 이하 실시예를 참조하여 본 발명의 내용을 상술하지만, 본 발명의 범주가 그것에 의해 한정되는 것은 아니다.The cosmetically effective amount refers to the amount of the active ingredient that is effective in improving the nutritional status related to the beauty of the object such as the health condition of the skin and the health condition of the hair and at the same time, do. The nutritional effective amount and the cosmetically effective amount may be variably determined by various factors such as the use and properties of the composition to be used, so that the effective amount need not be particularly limited. Thus, the composition according to the present invention may contain, depending on its use, for example, a pharmaceutical composition comprising a pharmaceutically acceptable carrier, a food comprising a nutraceutically acceptable carrier, a feed additive or beverage composition, And a cosmetic composition containing a carrier that is acceptable as a cosmetic composition. Hereinafter, the content of the present invention will be described with reference to Examples, but the scope of the present invention is not limited thereto.
[실험예 1] 아연-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 1] Preparation of zinc-aspartic acid metal mineral diaminate
산화아연 8g과 아스파르트산 27g 을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 산화아연 용액과 아스파르트산 용액을 혼합한 뒤 불순물을 제거하기 위해 여과하였다. 여과된 아연 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 그런 다음, 반응액을 분무건조하여 약 30 g의 아연-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 도 2는 분무건조를 이용하여 제조한 아연 아스파르트산 디아미네이트의 사진이다.8 g of zinc oxide and 27 g of aspartic acid were dissolved in 500 ml of solvent, respectively. The dissolved zinc oxide solution and the aspartic acid solution were mixed and then filtered to remove impurities. The filtered zinc aspartic acid solution was reacted with stirring at 60 캜. Then, the reaction solution was spray-dried to obtain about 30 g of zinc-aspartic acid metal mineral diamine powder. 2 is a photograph of a zinc aspartate diaminate prepared by spray drying.
[실험예 2] 아연-글루탐산 금속 미네랄 디아미네이트의 제조[Experimental Example 2] Preparation of zinc-glutamic acid metal mineral diaminate
산화아연 8g과 글루탐산 30g 을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 산화아연 용액과 글루탐산 용액을 혼합한 뒤 불순물을 제거하기 위해 여과하였다. 여과된 아연과 글루탐산 용액을 60℃에서 교반하면서 반응시켰다. 그런 다음, 반응액을 분무건조하여 약 25 g의 아연-글루탐산 금속 미네랄 디아미네이트 분말을 얻었다. 8 g of zinc oxide and 30 g of glutamic acid were respectively dissolved in 500 ml of a solvent. The dissolved zinc oxide solution and the glutamic acid solution were mixed and then filtered to remove impurities. The filtered zinc and glutamic acid solutions were allowed to react at 60 < 0 > C with stirring. Then, the reaction solution was spray-dried to obtain about 25 g of zinc-glutamate metal mineral diaminate powder.
[실험예 3] 아연-메치오닌 금속 미네랄 디아미네이트의 제조[Experimental Example 3] Preparation of zinc-methionine metal mineral diaminate
산화아연 8g과 메치오닌 30g 을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 산화아연 용액과 메치오닌 용액을 혼합한 뒤 불순물을 제거하기 위해 여과하였다. pH가 4.5~6.5범위가 되도록 염산(HCl) 적정량을 점적하면서 반응액을 산성조건으로 만들었다. 여과된 아연과 메치오닌 용액을 60℃에서 교반하면서 반응시켰다. 그런 다음, 반응액을 분무건조하여 약 28 g의 아연-메치오닌 금속 미네랄 디아미네이트 분말을 얻었다. 8 g of zinc oxide and 30 g of methionine were dissolved in 500 ml of solvent water, respectively. The dissolved zinc oxide solution and the methionine solution were mixed and then filtered to remove impurities. The reaction solution was acidified while dropping an appropriate amount of hydrochloric acid (HCl) so that the pH was in the range of 4.5 to 6.5. The filtered zinc and methionine solution was allowed to react at 60 < 0 > C with stirring. Then, the reaction solution was spray-dried to obtain about 28 g of zinc-methionine metal mineral diaminate powder.
[실험예 4] 아연-글리신 금속 미네랄 디아미네이트의 제조[Experimental Example 4] Preparation of zinc-glycine metal mineral diaminate
산화아연 8g과 글리신 16g 을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 산화아연 용액과 글리신 용액의 불순물을 제거하기 위해 여과하였다. pH가 4.5~6.5범위가 되도록 염산(HCl) 적정량을 점적하면서 반응액을 산성조건으로 만들었다. 여과된 아연과 글리신 용액을 60℃에서 교반하면서 반응시켰다. 그런 다음, 반응액을 분무건조하여 약 17 g의 아연-글리신 금속 미네랄 디아미네이트 분말을 얻었다. 8 g of zinc oxide and 16 g of glycine were dissolved in 500 ml of a solvent, respectively. The dissolved zinc oxide solution and the glycine solution were filtered to remove impurities. The reaction solution was acidified while dropping an appropriate amount of hydrochloric acid (HCl) so that the pH was in the range of 4.5 to 6.5. The filtered zinc and glycine solutions were reacted at 60 < 0 > C with stirring. Then, the reaction solution was spray-dried to obtain about 17 g of zinc-glycine metal mineral diaminate powder.
[실험예 5] 아연-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 5] Preparation of zinc-aspartic acid metal mineral diaminate
글루콘산아연 46 g과 아스파르트산 27 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 글루콘산아연 용액과 아스파르트산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 아연과 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 55 g의 아연-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 46 g of zinc gluconate and 27 g of aspartic acid were respectively dissolved in 500 ml of a solvent water. The dissolved zinc gluconate solution and the aspartic acid solution were filtered to remove impurities. The filtered zinc and aspartic acid solutions were reacted with stirring at 60 < 0 > C. The reaction solution was spray-dried to obtain about 55 g of zinc-aspartic acid metal mineral diamine powder.
[실험예 6] 철-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 6] Preparation of iron-aspartic acid metal mineral diaminate
젖산철 24 g과 아스파르트산 27 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 젖산철 용액과 아스파르트산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 철과 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 35 g의 철-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 24 g of ferrous lactate and 27 g of aspartic acid were respectively dissolved in 500 ml of a solvent water. The dissolved ferric lactate solution and the aspartic acid solution were filtered to remove impurities. The filtered iron and aspartic acid solutions were reacted with stirring at 60 < 0 > C. The reaction solution was spray-dried to obtain about 35 g of iron-aspartic acid metal mineral diamine powder.
[실험예 7] 철-글루탐산 금속 미네랄 디아미네이트의 제조[Experimental Example 7] Preparation of iron-glutamic acid metal mineral diaminate
젖산철 24 g과 글루탐산 30 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 젖산철 용액과 글루탐산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 철과 글루탐산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 30 g의 철-글루탐산 금속 미네랄 디아미네이트 분말을 얻었다. 24 g of ferrous lactate and 30 g of glutamic acid were dissolved in 500 ml of a solvent, respectively. The dissolved iron lactate solution and the glutamic acid solution were filtered to remove impurities. The filtered iron and glutamic acid solution were reacted at 60 캜 with stirring. The reaction solution was spray-dried to obtain about 30 g of iron-glutamate metal mineral diamine powder.
[실험예 8] 철-메치오닌 금속 미네랄 디아미네이트의 제조[Experimental Example 8] Preparation of Iron-Methionine Metal Mineral Diaminate
젖산철 24 g과 메치오닌 30 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 젖산철 용액과 메치오닌 용액의 불순물을 제거하기 위해 여과하였다. 여과된 철과 메치오닌 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 28 g의 철-메치오닌 금속 미네랄 디아미네이트 분말을 얻었다. 24 g of ferrous lactate and 30 g of methionine were each dissolved in 500 ml of a solvent water. The dissolved iron lactate solution and the methionine solution were filtered to remove impurities. The filtered iron and methionine solution were reacted with stirring at 60 ° C. The reaction solution was spray-dried to obtain about 28 g of iron-methionine metal mineral diamine powder.
[실험예 9] 철-글리신 금속 미네랄 디아미네이트의 제조[Experimental Example 9] Preparation of Iron-Glycine Metal Mineral Diaminate
젖산철 24 g과 글리신 16 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 젖산철 용액과 글리신 용액의 불순물을 제거하기 위해 여과하였다. 여과된 젖산철과 글리신 용액을 60℃에서 교반하면서 반응시켰다. 반응을 분무건조하여 약 22 g의 철-글리신 금속 미네랄 디아미네이트 분말을 얻었다. 24 g of ferrous lactate and 16 g of glycine were each dissolved in 500 ml of a solvent water. The dissolved iron lactate solution and the glycine solution were filtered to remove impurities. The filtered ferric lactate and glycine solution were reacted at 60 DEG C with stirring. The reaction was spray dried to give about 22 g of iron-glycine metal mineral diaminate powder.
[실험예 10] 철-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 10] Preparation of iron-aspartic acid metal mineral diaminate
구연산철 25 g과 아스파르트산 27 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 젖산철 용액과 아스파르트산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 철과 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 반응을 분무건조하여 약 13 g의 철-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 25 g of iron citrate and 27 g of aspartic acid were respectively dissolved in 500 ml of a solvent water. The dissolved ferric lactate solution and the aspartic acid solution were filtered to remove impurities. The filtered iron and aspartic acid solutions were reacted with stirring at 60 < 0 > C. The reaction was spray dried to obtain about 13 g of iron-aspartic acid metal mineral diaminate powder.
[실험예 11] 마그네슘-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 11] Preparation of magnesium-aspartic acid metal mineral diaminate
수산화마그네슘 6 g과 아스파르트산 27 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 수산화마그네슘 용액과 아스파르트산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 마그네슘과 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 25 g의 마그네슘-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 6 g of magnesium hydroxide and 27 g of aspartic acid were each dissolved in 500 ml of a solvent water. The dissolved magnesium hydroxide solution and the aspartic acid solution were filtered to remove impurities. The filtered magnesium and aspartic acid solutions were reacted with stirring at 60 < 0 > C. The reaction solution was spray-dried to obtain about 25 g of magnesium-aspartic metal mineral diamine powder.
[실험예 12] 망간-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 12] Preparation of manganese-aspartic acid metal mineral diaminate
황산망간 15 g과 아스파르트산 27 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 황산망간 용액과 아스파르트산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 망간과 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 27 g의 칼슘-글루탐산 금속 미네랄 디아미네이트 분말을 얻었다. 도 3은 분무건조를 이용하여 제조한 망간 아스파르트산 디아미네이트의 사진이다.15 g of manganese sulfate and 27 g of aspartic acid were each dissolved in 500 ml of a solvent water. The dissolved manganese sulfate solution and the aspartic acid solution were filtered to remove impurities. The filtered manganese and aspartic acid solutions were reacted with stirring at 60 < 0 > C. The reaction solution was spray-dried to obtain about 27 g of calcium-glutamate metal mineral diaminate powder. Figure 3 is a photograph of manganese aspartic acid diaminate prepared by spray drying.
[실험예 13] 칼슘-글루탐산 금속 미네랄 디아미네이트의 제조[Experimental Example 13] Preparation of calcium-glutamic acid metal mineral diaminate
산화칼슘 6 g과 글루탐산 30 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 산화칼슘 용액과 글루탐산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 칼슘과 글루탐산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 75 g의 망간-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 도 4는 분무건조를 이용하여 제조한 칼슘 글루탐산 디아미네이트의 사진이다.6 g of calcium oxide and 30 g of glutamic acid were respectively dissolved in 500 ml of a solvent. The dissolved calcium oxide solution and the glutamic acid solution were filtered to remove impurities. The filtered calcium and glutamic acid solutions were allowed to react at 60 DEG C with stirring. The reaction solution was spray-dried to obtain about 75 g of manganese-aspartic acid metal mineral diamine powder. 4 is a photograph of calcium glutamic acid diaminate prepared by spray drying.
[실험예 14] 구리-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 14] Preparation of copper-aspartic acid metal mineral diaminate
황산동 16 g과 아스파르트산 27 g을 각각 500 ㎖의 용매 물에 용해하였다. 상기 용해된 황산동 용액과 아스파르트산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 구리와 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 28 g의 구리-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 16 g of copper sulfate and 27 g of aspartic acid were respectively dissolved in 500 ml of a solvent water. The solution was filtered to remove impurities of the dissolved copper sulfate solution and the aspartic acid solution. The filtered copper and aspartic acid solutions were reacted with stirring at 60 < 0 > C. The reaction solution was spray-dried to obtain about 28 g of a copper-aspartic acid metal mineral diamine powder.
[실험예 15] 크롬-아스파르트산 금속 미네랄 디아미네이트의 제조[Experimental Example 15] Preparation of chromium-aspartic acid metal mineral diaminate
염화크롬 13 g과 아스파르트산 27 g을 각각 500 ㎖의 용매 물에 용해하였다.상기 용해된 염화크롬 용액과 아스파르트산 용액의 불순물을 제거하기 위해 여과하였다. 여과된 크롬과 아스파르트산 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 20 g의 크롬-아스파르트산 금속 미네랄 디아미네이트 분말을 얻었다. 13 g of chromium chloride and 27 g of aspartic acid were respectively dissolved in 500 ml of a solvent, and the solution was filtered to remove impurities of the dissolved chromium chloride solution and aspartic acid solution. The filtered chromium and aspartic acid solutions were reacted with stirring at 60 < 0 > C. The reaction solution was spray-dried to obtain about 20 g of chromium-aspartic acid metal mineral diamine powder.
[실험예 16] 미네랄 복합체-아미노산 미네랄 디아미네이트의 제조[Experimental Example 16] Preparation of mineral complex-amino acid mineral diaminate
산화아연, 젖산철, 수산화마그네슘, 황산망간, 황산동 및 염화크롬 각 5g씩 30g을 2,000 ㎖의 물에 넣어 충분히 교반하여 용해하였다. 또한, 아스파르트산, 글루탐산, 메치오닌 및 글리신 각 10g씩 40 g을 넣어 물에 넣어 충분히 교반하여 용해하였다. 미네랄원과 아미노산 용액은 pH가 4.5~6.5범위가 되도록 염산(HCl) 적정량을 점적하면서 산성조건으로 만들었다. 충분히 용해한뒤, 불순물을 여과하여 제거하였다. 여과된 각 용액을 60℃에서 교반하면서 반응시켰다. 반응액을 분무건조하여 약 70 g의 수용성 복합 미네랄-아미노산 미네랄 디아미네이트를 얻었다.30 g of each of 5 g of each of zinc oxide, iron lactate, magnesium hydroxide, manganese sulfate, copper sulfate and chromium chloride was added to 2,000 ml of water and sufficiently dissolved by stirring. Further, 40 g of each of 10 g of aspartic acid, glutamic acid, methionine and glycine was added, and the mixture was sufficiently dissolved by stirring. The mineral source and amino acid solutions were made acidic by dropping the appropriate amount of hydrochloric acid (HCl) so that the pH was in the range of 4.5 to 6.5. After sufficiently dissolving, the impurities were removed by filtration. Each filtered solution was reacted with stirring at 60 ° C. The reaction solution was spray-dried to obtain about 70 g of a water-soluble complex mineral-amino acid mineral diaminate.
[실험예 17] 관능 시험[Experimental Example 17]
시판되고 있는 미에로화이바(현대약품)에 실험예 1 내지 16에서 얻어진 미네랄 디아미네이트 화합물을 첨가하여, 물성 및 맛에 미치는 영향을 확인하였다. 미네랄 디아미네이트 화합물을 1% 첨가하였을 때 미치는 영향을 검증하기 위하여, 전문 관능 검사요원 10 명을 상대로 실험예 1 내지 16에서 얻은 시료 수용액의 맛, 외관 및 종합적 평가에 대한 관능시험을 실시하였다. 이때 맛은 쓴맛, 떫은맛 및 텁텁한 맛에 각각 매우 약함(1), 약함(2), 보통(3), 강함(4), 아주 강함(5)의 5 점을 배점하는 방식으로 실시하였고, 외관은 색깔 및 청징도와 종합적 평가를 각각 아주 나쁨(1), 나쁨(2), 보통(3), 좋음(4), 아주 좋음(5)의 5 점을 배점하는 방식으로 실시하였다. 맛의 평가는 하기 표 1에 나타내었으며, 외관의 평가는 하기 표 2에 나타내었다.The mineral diiminate compounds obtained in Experimental Examples 1 to 16 were added to commercially available Mierofhaiba (Hyundai Pharm) to confirm the effect on physical properties and taste. In order to examine the effect of 1% addition of the mineral diaminate compound, 10 taste sensory evaluations were conducted on the taste, appearance and comprehensive evaluation of the sample aqueous solutions obtained in Experimental Examples 1 to 16 against 10 special sensory test agents. At this time, the taste was evaluated by scoring five points of very weak (1), weak (2), normal (3), strong (4), and very strong (5) for bitter taste, pungent taste and strong taste. Color and clarification and comprehensive evaluation were performed in such a way as to score 5 points of very poor (1), poor (2), normal (3), good (4) and excellent (5). The evaluation of taste is shown in Table 1 below, and the evaluation of appearance is shown in Table 2 below.
맛 평가Taste evaluation
조성물Composition 맛의 특성Characteristics of taste 종합적 평가Comprehensive evaluation
쓴맛bitter 떫은맛A bitter taste 텁텁한맛Tough taste
1One 1.51.5 1.41.4 1.41.4 1.431.43
22 1.01.0 1.21.2 1.11.1 1.101.10
33 1.31.3 1.21.2 1.21.2 1.231.23
44 0.80.8 0.90.9 0.90.9 0.870.87
55 1.21.2 1.11.1 1.11.1 1.131.13
66 1.31.3 1.11.1 1.21.2 1.201.20
77 1.41.4 1.21.2 1.51.5 1.371.37
88 1.01.0 1.31.3 0.80.8 1.031.03
99 0.80.8 1.51.5 0.70.7 0.900.90
1010 1.11.1 0.70.7 1.01.0 0.930.93
1111 1.21.2 1.11.1 1.11.1 1.131.13
1212 1.21.2 1.41.4 1.31.3 1.301.30
1313 1.51.5 1.01.0 1.01.0 1.171.17
1414 1.11.1 1.41.4 1.41.4 1.301.30
1515 1.21.2 1.21.2 1.01.0 1.031.03
1616 1.01.0 1.21.2 0.80.8 1.001.00
미에로화이바Miero Faiba 0.90.9 1.11.1 1.01.0 1.001.00
외관 평가Appearance evaluation
조성물Composition 맛의 특성Characteristics of taste 종합적 평가Comprehensive evaluation
색color 청정도cleanliness
1One 4.54.5 4.24.2 4.354.35
22 4.14.1 4.04.0 4.054.05
33 4.44.4 4.14.1 4.254.25
44 4.34.3 4.04.0 4.154.15
55 4.54.5 4.64.6 4.554.55
66 4.64.6 4.34.3 4.454.45
77 4.54.5 4.44.4 4.454.45
88 4.14.1 4.24.2 4.154.15
99 4.24.2 4.04.0 4.104.10
1010 4.54.5 4.64.6 4.554.55
1111 4.74.7 4.54.5 4.604.60
1212 4.64.6 4.14.1 4.354.35
1313 4.64.6 4.04.0 4.304.30
1414 4.54.5 4.24.2 4.354.35
1515 4.34.3 4.34.3 4.304.30
1616 4.24.2 4.24.2 4.204.20
미에로화이봐Mierohana Hey 4.54.5 4.44.4 4.454.45
그 결과, 본 발명에 따른 미네랄 디아미네이트 화합물은 첨가하는 대상물의 물성(맛, 외관 등)에 거의 영향을 미치지 않는 것으로 확인되었다.As a result, it was confirmed that the mineral diiminate compound according to the present invention hardly affected the physical properties (taste, appearance, etc.) of the object to be added.
[실험예 18] 칼슘-글루탐산 미네랄 디아미네이트의 식품 첨가물로서의 응용[Experimental Example 18] Application of calcium-glutamic acid mineral diaminate as a food additive
실험예 13의 디아미네이트 화합물 99.5 중량%에 5-리보뉴클레오티드 0.5 중량%를 혼합하여 분말 상 혼합물을 만들고, 그 것의 맛을 확인하여 본 결과, 기존 조미료인 글루타민산나트륨과 동일한 맛을 발휘함을 확인하였다. 따라서, 본 발명의 디아미네이트 화합물은 조미료로서의 활용에 문제가 없음이 확인되었다.A powder mixture was prepared by mixing 0.5% by weight of 5-ribonucleotide with 99.5% by weight of the diaminate compound of Experimental Example 13, and the taste thereof was confirmed. As a result, it was confirmed that the same taste as that of sodium glutamate Respectively. Therefore, it was confirmed that the diaminate compound of the present invention had no problem in utilization as a seasoning.
[실험예 19] 칼슘-글루탐산 미네랄 디아미네이트의 음료에의 적용[Experimental Example 19] Application of calcium-glutamic acid mineral diaminate to beverage
우유 100 g에 실험예 13에서 얻어진 미네랄 디아미네이트 화합물을 혼합하여 장시간 유지한 결과, 침전이 전혀 형성되지 않으며 맛에도 영향을 주지 않았다.The mineral diaminate compound obtained in Experimental Example 13 was mixed with 100 g of milk and kept for a long time. As a result, no precipitation was formed and no influence on the taste was observed.
[실험예 20] 화장품에의 적용[Experimental Example 20] Application to cosmetics
실험예 1에서 얻어진 미네랄 디아미네이트 화합물을 함유한 화장품(lotion type)을 제조하여 장시간 유지한 결과, 변색이 없었으며, 피부에 사용하여도 전혀 문제점이 없었다.The cosmetic lotion type containing the mineral diaminate compound obtained in Experimental Example 1 was prepared and maintained for a long time, and as a result, there was no discoloration and there was no problem even if it was used for skin.
실시예 4. 우리딘이 포함된 금속 미네랄 디아미네이트 복합조성물의 항염증 실험Example 4. Anti-inflammatory experiment of metal mineral diaiminate composite composition containing uridine
리포폴리사카라이드(lipopolysaccharide, LPS)는 그람 음성균의 외막 구성성분으로, 세포에 처리되면 염증을 유발하여 세포 내 산화질소(nitricoxide, NO) 생성을 유도하게 된다. 생성된 산화질소는 주변 세포에게 염증반응을 유도하여 전염증성 자극을 유발하기 때문에 산화질소 생성을 억제하는 것은 염증성 질환의 치료에 있어서 중요하다. 따라서, 우리딘이 포함된 금속 미네랄 디아미네이트 복합조성물의 항염증 효과를 검토하기 위해, 복합조성물이 처리된 RAW 264.7 세포에 리포폴리사카라이드를 처리한 뒤 생성되는 산화질소 정도를 관찰하였다.Lipopolysaccharide (LPS) is an outer membrane component of Gram-negative bacteria. When treated with cells, it induces inflammation and induces nitric oxide (NO) production. Since the produced nitric oxide induces inflammatory response to peripheral cells and induces proinflammatory stimulation, inhibition of nitric oxide production is important in the treatment of inflammatory diseases. Therefore, in order to examine the anti-inflammatory effect of the metal mineral diaiminate composite composition containing uridine, the degree of nitric oxide produced after lipopolysaccharide treatment of RAW 264.7 cells treated with the composite composition was observed.
1) 세포 배양1) Cell culture
항염증 효과 검증 실험에 사용한 RAW 264.7 대식세포는 한국 세포주 은행(Korean Cell Line Bank)으로부터 분양받았다. RAW264.7 대식세포를 10% 소태아혈청 (fetal bovine serum, FBS), 1% 페니실린(penicillin) 및 1% 스트렙토마이신(streptomycin)이 첨가된 둘베코 변형 이글스 최소영양배지(dulbecco modified Eagle minimal essential medium, DMEM)에 접종한 뒤, 37℃의 5% 이산화탄소 조건에서 24시간동안 배양하였다. 배지는 2일 마다 교체해주었다.RAW 264.7 macrophages used for the anti-inflammatory effect test were distributed from the Korean Cell Line Bank. RAW264.7 macrophages were cultured in Dulbecco's modified Eagle minimal essential medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin and 1% streptomycin , DMEM), and then cultured at 37 ° C under 5% carbon dioxide for 24 hours. The badge was changed every 2 days.
2) 아연 아스파테이트 디아미네이트 제조2) Preparation of zinc aspartate diaminate
상기 실험예 1의 아연 아스파테이트 제조방법과 동일한 방법으로 제조하였다. 제조된 아연 아스파테이트 디아미네이트에 3차 증류수를 첨가하여 1 mg/ml이 되도록하여 저장용액 (stock solution)으로 사용하였으며, 4℃ 에서 보관하였다.Was prepared in the same manner as in the zinc aspartate production method of Experimental Example 1 above. The prepared zinc aspartate diaminate was used as a stock solution at a concentration of 1 mg / ml by adding tertiary distilled water and stored at 4 ° C.
3) 산화질소(nitric oxide, NO) 생성 억제 효과 검증3) Verification of nitric oxide (NO) production inhibitory effect
RAW 264.7 세포를 24 웰 플레이트(well plate)에 2.5 ×10 5 cells/ml로 분주하고 37℃의 5% 이산화탄소 조건에서 24시간동안 배양하였다. 배양액에 아연 아스파테이트 디아미네이트를 각각 25, 50, 100 및 200 ug/ml가 되도록 처리하고, 우리딘 100 ug/ml가 되도록 첨가하였다. 그런 다음, 1시간 후에 리포폴리사카라이드(lipopolysaccharide, LPS)를 200 ng/ml로 처리하여 24시간 배양하였다. 배양액 100 ul와 그리스(griess) 시약(2.5 % 인산 용액 내에 1% 술파닐아미드 및 0.1% 나프틸에틸렌 디아민 함유) 100 ul를 혼합하여 어두운 곳에서 10분 동안 반응시킨 후 분광광도계를 사용하여 540nm에서 흡광도를 측정하였다. 그리스 시약은 배양액에 생성된 산화질소를 아질산염(nitrite)으로 전환시키며, 분광광도계를 사용하여 전환된 아질산염을 540 nm 파장에서 흡광도를 측정함으로 산화질소의 생성정도(%)를 비교할 수 있다. 아무것도 처리하지 않은 RAW 264.7 세포를 음성대조군, 리포폴리사카라이드200 ng/ml만 처리한 RAW 264.7 세포를 양성대조군, 아연 아스파테이트 디아미네이트 각각 25, 50, 100 및 200 ug/ml에 우리딘 100 ug/ml을 처리하고 1시간 후에 리포폴리사카라이드 200 ng/ml를 처리한 RAW 264.7 세포를 각각 실험군 1, 2, 3 및 4라고 정하였다. 도 5는 아연 아스파테이트 디아미네이트가 리포폴리사카라이드가 처리된 RAW 264.7 세포의 산화질소 생성에 미치는 효과를 나타낸 도면이다. 그 결과, 양성대조군과 비교하였을 때, 실험군 3 및 실험군 4에서 산화질소 생성이 약 60% 억제되었다. 따라서, 우리딘이 포함된 아연 아스파르트산 디아미네이트 복합조성물을 염증반응이 유도된 RAW 264.7 세포에 처리하였을 때, 염증반응을 유도하는 산화질소의 생성이 억제되었으므로 항염증에 우수한 효과가 있는 것을 확인하였다. 상기 우리딘 이외에 우리딘 유도체인 우리딘인산, 우라실(uracil), 우리딘모노포스페이트(uridine monophosphate), 우리딘디포스페이트(uridine diphosphate), 트리아세틸 우리딘(triacetyl uridine), 트리벤조닐 우리딘(tribenzonyl uridine), 5-에틸 우리딘(5-ethyl uridine), 2-데옥시우리딘(2-deoxyuridine) 또는 아이소프로필리딘 우리딘 (isopropylidene uridine) 등을 사용할 수 있다.RAW 264.7 cells were plated at 2.5 × 10 5 cells / ml in a 24-well plate and cultured at 37 ° C. under 5% carbon dioxide for 24 hours. To the culture, zinc aspartate diaminate was treated to 25, 50, 100 and 200 ug / ml, respectively, and added to 100 ug / ml of uridine. Then, 1 hour later, lipopolysaccharide (LPS) was cultured at 200 ng / ml for 24 hours. 100 μl of the culture solution and 100 μl of a griess reagent (containing 1% sulfanilamide and 0.1% naphthylethylenediamine in a 2.5% phosphoric acid solution) were mixed in a dark place for 10 minutes, and then the resultant was subjected to a spectrophotometer at 540 nm Absorbance was measured. The Greek reagent converts the nitric oxide produced in the culture medium to nitrite, and the conversion of nitrite converted to nitrite using a spectrophotometer can be compared with the rate of production of nitric oxide by measuring the absorbance at 540 nm wavelength. RAW 264.7 cells treated with nothing were treated with negative control, RAW 264.7 cells treated with only 200 ng / ml of lipopolysaccharide were treated with positive control, zinc ascapartate diaminate 25, 50, 100 and 200 ug / ml each of uridine 100 RAW 264.7 cells treated with 200 ng / ml of lipopolysaccharide after one hour of treatment with ug / ml were designated Experimental Groups 1, 2, 3 and 4, respectively. Figure 5 shows the effect of zinc aspartate diaminate on the production of nitric oxide of RAW 264.7 cells treated with lipopolysaccharide. As a result, nitric oxide production was inhibited by about 60% in the experimental group 3 and the experimental group 4 when compared with the positive control group. Therefore, it has been confirmed that the zinc aminosulfate diaminadate composite composition containing uridine is treated with RAW 264.7 cells induced by inflammation to inhibit the production of nitric oxide inducing an inflammatory reaction, thus showing excellent effects on anti-inflammation Respectively. In addition to the uridine, uridine derivatives uridine phosphate, uracil, uridine monophosphate, uridine diphosphate, triacetyl uridine, tribenzonyl uridine, uridine, 5-ethyl uridine, 2-deoxyuridine, or isopropylidene uridine may be used.

Claims (16)

  1. 금속 미네랄원과 아미노산을 0.1 내지 70중량%의 농도로 용매에 첨가하여 금속 미네랄·단분자 아미노산 용액을 제조하거나 각각의 용액을 제조하여 혼합하는 단계; 상기 제조된 금속 미네랄·아미노산 용액을 일정시간 산성의 조건하에서 반응시키는 단계; 및 건조하여 분말화하는 단계; 를 포함하는 금속 미네랄 디아미네이트의 제조방법.Adding a metal mineral source and an amino acid in a concentration of 0.1 to 70% by weight to a solvent to prepare a metal mineral / mono-molecular amino acid solution or preparing and mixing each solution; Reacting the prepared metal mineral amino acid solution under an acidic condition for a predetermined time; And drying and pulverizing; ≪ / RTI >
  2. 금속 미네랄원과 아미노산을 0.1 내지 70중량%의 농도로 용매에 첨가하여 금속 미네랄·단분자 아미노산 용액을 제조하거나 각각의 용액을 제조하여 혼합하는 단계; 상기 금속 미네랄·아미노산 용액을 일정시간 교반하면서 40 내지 100℃로 가온하여 반응하는 단계; 및 건조하여 분말화하는 단계; 를 포함하는 금속 미네랄 디아미네이트의 제조방법Adding a metal mineral source and an amino acid in a concentration of 0.1 to 70% by weight to a solvent to prepare a metal mineral / mono-molecular amino acid solution or preparing and mixing each solution; Reacting the metal mineral / amino acid solution by heating at 40 to 100 占 폚 with stirring for a predetermined time; And drying and pulverizing; METHOD FOR PRODUCING METAL MINERAL DIAMONATE
  3. 청구항 1 또는 2항 중 어느 하나의 항에 있어서, The method according to any one of claims 1 to 3,
    상기 금속 미네랄 용액과 아미노산 용액은 금속 미네랄원의 미네랄과 아미노산의 몰비를 기준으로 1 : 1 내지 4의 비율로 혼합제조된 것임 것을 특징으로 하는, 금속 미네랄 디아미네이트의 제조방법.Wherein the metal mineral solution and the amino acid solution are mixed at a ratio of 1: 1 to 4 based on the molar ratio of the mineral and amino acid of the mineral mineral source.
  4. 청구항 1 또는 2항 중 어느 하나의 항에 있어서, The method according to any one of claims 1 to 3,
    상기 아미노산이 알칼리성 아미노산인 경우, 상기 아미노산 용액의 산도를 완충용액을 사용하여 pH4 ~ 8로 조절하는 단계를 더 포함하는 것을 특징으로 하는, 금속 미네랄 디아미네이트의 제조방법.Wherein the pH of the amino acid solution is adjusted to pH 4 to 8 by using a buffer solution when the amino acid is an alkaline amino acid.
  5. 청구항 1 또는 2항 중 어느 하나의 항에 있어서, The method according to any one of claims 1 to 3,
    상기 금속 미네랄·아미노산 용액을 여과하는 단계를 더 포함하는 것을 특징으로 하는 금속 미네랄 디아미네이트의 제조방법.Further comprising the step of filtering the metal mineral / amino acid solution.
  6. 청구항 1 또는 2항 중 어느 하나의 항에 있어서, The method according to any one of claims 1 to 3,
    상기 금속 미네랄·아미노산 용액을 농축하는 단계를 더 포함하는 것을 특징으로 하는 금속 미네랄 디아미네이트의 제조방법. Further comprising concentrating the metal mineral / amino acid solution. ≪ RTI ID = 0.0 > 11. < / RTI >
  7. 청구항 1 또는 2항 중 어느 하나의 항에 있어서,The method according to any one of claims 1 to 3,
    상기 금속 아미노산은 산성 아미노산임을 특징으로 하는, 금속 미네랄 디아미네이트의 제조방법.Wherein the metal amino acid is an acidic amino acid.
  8. 청구항 1 또는 2항 중 어느 하나의 항에 있어서,The method according to any one of claims 1 to 3,
    상기 금속 미네랄원과 아미노산은 각각 1종 이상을 포함하는 것을 특징으로 하는, 금속 미네랄 디아미네이트의 제조방법.Wherein the metal mineral source and the amino acid each contain at least one kind of metal mineral source and amino acid.
  9. 청구항 1 또는 2항 중 어느 하나의 항에 있어서,The method according to any one of claims 1 to 3,
    상기 건조는 감압건조, 동결건조 또는 분무건조(spray-drying)방법 중에서 선택된 어느 하나인 것을 특징으로 하는, 금속 미네랄 디아미네이트의 제조방법.Wherein the drying is selected from the group consisting of vacuum drying, freeze drying, and spray-drying.
  10. 청구항 1 내지 9항 중 어느 하나의 항에 있어서,The method according to any one of claims 1 to 9,
    상기 용매는 물, 알칼리성 용매, 산성용매 또는 유기용매 중에서 선택된 어느 하나인 것을 특징으로 하는, 금속 미네랄 디아미네이트의 제조방법.Wherein the solvent is any one selected from water, an alkaline solvent, an acidic solvent, and an organic solvent.
  11. 청구항 1 또는 2항 중 어느 하나의 항에 있어서,The method according to any one of claims 1 to 3,
    상기 금속 미네랄 디아미네이트는 구리 글루타메이트/아스파테이트(cooper glutamate/aspartate), 구리 비스글루타메이트(cooper bisglutamate), 구리 비스아스파테이트(cooper bisaspartate), 아연 글루타메이트/아스파테이트(zinc glutamate/aspartate), 아연 비스글루타메이트(zinc bisglutamate), 아연 비스아스파테이트(zinc bisaspartate), 철 글루타메이트/아스파테이트(iron glutamate/aspartate), 철 비스글루타메이트(iron bisglutamate), 철 비스아스파테이트(iron bisaspartate), 철 비스글루타메이트/아스파테이트(iron bisglutamate/aspartate), 철 글루타메이트/비스아스파테이트(iron glutamate/ bisaspartate), 크롬 글루타메이트/아스파테이트(chromium glutamate/aspartate), 크롬 비스글루타메이트(chromium bisglutamate), 크롬 비스아스파테이트(chromium bisaspartate), 크롬 비스글루타메이트/아스파테이트(chromium bisglutamate/aspartate), 크롬 글루타메이트/비스아스파테이트 (chromium glutamate/ bisaspartate), 코발트 글루타메이트/아스파테이트(covalt glutamate/aspartate), 코발트 비스글루타메이트(covalt bisglutamate), 코발트 비스아스파테이트(covalt bisaspartate), 마그네슘 글루타메이트/스파테이트(magnesium glutamate/aspartate), 마그네슘 비스글루타메이트(magnesium bisglutamate), 마그네슘 비스아스파테이트(magnesium bisaspartate), 망간 글루타메이트/아스파테이트(manganese glutamate/aspartate), 망간 비스글루타메이트(manganese bisglutamate) 또는 망간 비스아스파테이트(manganese bisaspartate)에서 선택된 어느 하나인 것을 특징으로 하는, 금속 미네랄 디아미네이트의 제조방법The metal mineral diaminate is selected from the group consisting of copper glutamate / aspartate, cooper bisglutamate, cooper bisaspartate, zinc glutamate / aspartate, zinc bis But are not limited to, zinc bisglutamate, zinc bisaspartate, iron glutamate / aspartate, iron bisglutamate, iron bisaspartate, iron bisglutamate / aspartate iron bisglutamate / aspartate, iron glutamate / bisaspartate, chromium glutamate / aspartate, chromium bisglutamate, chromium bisaspartate, chromium glutamate / aspartate, ≪ RTI ID = 0.0 > Chromium bisglutamate / aspartate e), chromium glutamate / bisaspartate, covalt glutamate / aspartate, covalt bisglutamate, covalt bisaspartate, magnesium glutamate / for example, magnesium glutamate / aspartate, magnesium bisglutamate, magnesium bisaspartate, manganese glutamate / aspartate, manganese bisglutamate or manganese bisaspartate, bisaspartate), characterized in that the metal mineral diamine
  12. 청구항 1 또는 2항 중 어느 하나의 방법으로 제조된 전기적으로 중성인 금속 미네랄 디아미네이트.  An electrically neutral metallic mineral diaminate produced by the process of any one of claims 1 or 2.
  13. 청구항 9항에 있어서, The method of claim 9,
    상기 금속 미네랄 디아미네이트는 구리 글루타메이트/아스파테이트(cooper glutamate/aspartate), 구리 비스글루타메이트(cooper bisglutamate), 구리 비스아스파테이트(cooper bisaspartate), 아연 글루타메이트/아스파테이트(zinc glutamate/aspartate), 아연 비스글루타메이트(zinc bisglutamate), 아연 비스아스파테이트(zinc bisaspartate), 철 글루타메이트/아스파테이트(iron glutamate/aspartate), 철 비스글루타메이트(iron bisglutamate), 철 비스아스파테이트(iron bisaspartate), 철 비스글루타메이트/아스파테이트(iron bisglutamate/aspartate), 철 글루타메이트/비스아스파테이트(iron glutamate/ bisaspartate), 크롬 글루타메이트/아스파테이트(chromium glutamate/aspartate), 크롬 비스글루타메이트(chromium bisglutamate), 크롬 비스아스파테이트(chromium bisaspartate), 크롬 비스글루타메이트/아스파테이트(chromium bisglutamate/aspartate), 크롬 글루타메이트/비스아스파테이트 (chromium glutamate/ bisaspartate), 코발트 글루타메이트/아스파테이트(covalt glutamate/aspartate), 코발트 비스글루타메이트(covalt bisglutamate), 코발트 비스아스파테이트(covalt bisaspartate), 마그네슘 글루타메이트/아스파테이트(magnesium glutamate/aspartate), 마그네슘 비스글루타메이트(magnesium bisglutamate), 마그네슘 비스아스파테이트(magnesium bisaspartate), 망간 글루타메이트/아스파테이트(manganese glutamate/aspartate), 망간 비스글루타메이트(manganese bisglutamate) 또는 망간 비스아스파테이트(manganese bisaspartate)에서 선택된 어느 하나인 것을 특징으로 하는 금속 미네랄 디아미네이트.The metal mineral diaminate is selected from the group consisting of copper glutamate / aspartate, cooper bisglutamate, cooper bisaspartate, zinc glutamate / aspartate, zinc bis But are not limited to, zinc bisglutamate, zinc bisaspartate, iron glutamate / aspartate, iron bisglutamate, iron bisaspartate, iron bisglutamate / aspartate iron bisglutamate / aspartate, iron glutamate / bisaspartate, chromium glutamate / aspartate, chromium bisglutamate, chromium bisaspartate, chromium glutamate / aspartate, Chromium bisglutamate / aspartate te), chromium glutamate / bisaspartate, covalt glutamate / aspartate, covalt bisglutamate, covalt bisaspartate, magnesium glutamate / aspartate, for example, magnesium glutamate / aspartate, magnesium bisglutamate, magnesium bisaspartate, manganese glutamate / aspartate, manganese bisglutamate or manganese bisaspartate, bisaspartate. < RTI ID = 0.0 > 15. < / RTI >
  14. 우리딘 또는 우리딘 유도체와 금속 미네랄 디아미네이트를 포함하는 항염증 의약 조성물.An antiinflammatory pharmaceutical composition comprising a uridine or uridine derivative and a metal mineral diaminate.
  15. 우리딘 또는 우리딘 유도체와 금속 미네랄 디아미네이트를 포함하는 화장료 조성물.A cosmetic composition comprising a uridine or uridine derivative and a metallic mineral diaminate.
  16. 청구항 14항 또는 청구항 15항 중 어느 하나의 항에 있어서, The method according to any one of claims 14 to 15,
    상기 금속 미네랄 디아미네이트는 아연 글루타메이트/아스파테이트(zinc glutamate/aspartate), 아연 비스글루타메이트(zinc bisglutamate), 아연 비스아스파테이트(zinc bisaspartate) 중에 선택된 하나임을 특징으로 하는 조성물.Wherein the metal mineral diaminate is one selected from zinc glutamate / aspartate, zinc bisglutamate, and zinc bisaspartate.
PCT/KR2018/015552 2017-12-08 2018-12-07 Metal mineral diaminate and preparation method therefor WO2019112383A1 (en)

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CN113735729A (en) * 2021-08-03 2021-12-03 四川吉隆达生物科技集团有限公司 Production process of feed-grade ferrous glutamate

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EP1790348A2 (en) * 1999-05-05 2007-05-30 Srinivas Uppugunduri Use of uridine for the treatment of inflammations and/or hemostasis
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KR20000053094A (en) * 1996-11-07 2000-08-25 인스파이어 파마슈티컬스 인코퍼레이티드 Method of treating bronchitis with uridine triphosphates and related compounds
EP1790348A2 (en) * 1999-05-05 2007-05-30 Srinivas Uppugunduri Use of uridine for the treatment of inflammations and/or hemostasis
KR20040049294A (en) * 2002-12-05 2004-06-11 주식회사 엠디바이오알파 Method For Preparation Of Amino Acid Chelate
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US20150265647A1 (en) * 2012-09-28 2015-09-24 Tufts University Uridine diphosphate derivatives, prodrugs, compositions and uses thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113735729A (en) * 2021-08-03 2021-12-03 四川吉隆达生物科技集团有限公司 Production process of feed-grade ferrous glutamate

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