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CN105596358B - Compound capsule - Google Patents

Compound capsule Download PDF

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Publication number
CN105596358B
CN105596358B CN201610060285.7A CN201610060285A CN105596358B CN 105596358 B CN105596358 B CN 105596358B CN 201610060285 A CN201610060285 A CN 201610060285A CN 105596358 B CN105596358 B CN 105596358B
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Prior art keywords
capsule
vitamin
filler
grain
powder
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CN201610060285.7A
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CN105596358A (en
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李兴惠
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a kind of capsule, which includes capsule shells and is wrapped in the capsule shells and is in powder or granular filler；The capsule shells are using gelatin as gelatin hollow capsule made of key component, and the filler includes active material and pharmaceutic adjuvant.Present invention proportioning science, reasonable, the stability of product is good, has no toxic side effect, safe, has good biological effect, can apply and prepare treatment Chronic Liver, kidney diaseases drug, in alleviation and elimination training physical fatigue food.Capsule of the present invention has the characteristics that be better than the prior art.

Description

Compound capsule
Technical field
The present invention relates to a kind of capsule medicaments and preparation method thereof, are to be related to a kind of including 8 kinds of amino acid and 11 specifically The capsule of kind vitamin micro pill, also referred to as compound amino acid capsule, further relate to the preparation method of the capsule.
Background technology
Protein is the material base of human life activity, human body items physiological function, especially immune function, cell damage The repair function and growth and development function of wound, with its be metabolized it is normal whether have extremely close relationship.Under normal circumstances, people Body is to obtain various amino acid by the protein in food to ensure the normal of body protein metabolism.It is closed in human body protein At in required 20 kinds of amino acid, wherein it is essential amino acid to have 8 kinds of amino acid, this 8 kinds of amino acid are that body is interior originally Body cannot synthesize and be necessarily dependent upon external supply.They are isoleucine, leucine, lysine, phenylalanine, Soviet Union's ammonia Acid, valine, methionine and tryptophan.Protein is synthesized, this 8 kinds of amino acid are indispensable, and in content deficiency Or the synthesis of protein can be all influenced when matching unbalanced.
The generation of disease, development and recovery from illness during, due to various pathology and stress reaction, it is in addition improper diet or Digestive tract function is affected, and usually will appear the disorder of protein metabolism, and the disorder of protein metabolism is often led with disease The duration of the death of cause, the generation of complication and disease is closely related.Therefore, in clinical practice, the supply of nitrogen matter is Indispensable, effective treatment means.
Since World War II, the U.S. takes the lead in releasing protein hydrolysate, the supply for nitrogen matter in lysis.50 In the age, Japan realizes the large scale fermentation of amino acid and prepared by purifying, and advantageous skill is provided for crystal type amino acid transfusion Art ensures.Into the 1970s and 1980s, amino acid transfusion constantly for clinically all kinds of acute diseases, seriously disease treatment, especially pair Urgent patient and the treatment for being unable to oral consumption patient provide strong support.
But for the treatment of chronic disease, especially can oral consumption patient treatment, the limitation right and wrong of amino acid transfusion It is often apparent.In terms of the characteristics of being metabolized from vivo acid, amino acid transfusion may cause vivo acid proportioning it is not normal, be infused Serum amino acid concentration declines rapidly, aggravates liver denitrogen and bear, simultaneously after serum amino acid excessive concentration in journey, infusion stop It is possible that causing the adverse reactions such as infusion reaction, vein blood vessel inflammation.What is more important amino acid transfusion is only in short In play the role of promote positive nitrogen equilibrium, be used for a long time therapeutic effect unobvious.
Just because of this, while parenteral nutrition develops, development abroad is simultaneously perfect by crystalline amino acid, hydrolysis egg In vain, a variety of enteral nutrition preparations of the nitrogen sources such as complete protein composition.Enteral nutrition preparation is mainly orally ingested, and providing must The nutrient needed meets the needs of body metabolism, and enteral nutrition is conducive to keep enteron aisle structure and function compared with parenteral nutrition Integrality prevents intestinal mucosa atrophy and bacterial translocation caused by long-term parenteral, is conducive to the immunity for improving body.
Currently, the treatment of enteral nutrition is paid much attention in clinical practice both at home and abroad, especially in the long-term treatment of chronic disease In, the ratio of enteral nutrition treatment greatly exceeds the treatment of parenteral nutrition.As long as " gastrointestinal function allows, and uses enteral as possible Nutrition " is the principle of clinic nutrition treatment.Therefore, people are badly in need of solving the drug for enteral nutrition treatment.Due to amino acid It is unstable, it causes Amino Acid Oral Preparation product stability poor, restricts the application of Amino Acid Oral Preparation product.For this purpose, this Field technology personnel attempt the new preparation comprising amino acid and vitamin of exploitation and have successfully pushed them to clinic.
Chinese Patent Application No. 021586195 (ten thousand Hes, CN1424027A) is related to a kind of composite amino acid capsule and its system Preparation Method.The invention product includes that a variety of supplementary materials such as 8 kinds of amino acid, 11 kinds of vitamin form, specific formula and preparation method, The invention product advantage is：Proportioning is reasonable, science, has good biological effect, technique uniqueness, advanced, convenient oral, nothing Toxic side effect, it is safe, it obtains doctor and patient welcomes.Product of the present invention is used for Chronic Liver, kidney and other disease treatments.
Chinese Patent Application No. 200410100003.9 (holy and, CN1781486A) discloses a kind of amino acid and dimension Raw cellulose capsule preparation, it includes amino acid coated granules and vitamin coated granule, wherein amino acid coated granule and vitamin The weight ratio of coated granule is 1: 0.68, wherein the amino acid coated granule includes isoleucine, leucine, the bad ammonia of hydrochloric acid Acid, phenylalanine, methionine, threonine, tryptophan, valine and R-gene, the vitamin coated granule include dimension Raw element B1 nitrate, vitamin B2, vitamin B6, Vitwas E and niacinamide.The invention, which additionally provides, prepares compound ammonia The method of base acid and vitamine capsule preparation.
Chinese Patent Application No. 200910153422.1 (Sai Li, CN102038691A) discloses a kind of vitamin amino acid Compound formulation is coated by multi-vitamins and compound amino acid and is prepared into pellet and obtains.It is believed that the dimension life obtained by the invention Plain amino acid composite preparation, is compounded with multivitamin and amino acid is easy to use, is improved using pellet sustained release coating technology Bioavilability, stable quality, absorption of human body are fast.
Chinese Patent Application No. 201010102505.0 (ten thousand Hes, CN101773512A) disclose a kind of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules and preparation method thereof, including 7 kinds of microspheric granulas, 7 kinds of microspheric granulas are by following parts by weight Raw material forms:2.66~9.9 parts of thiamine mononitrate pellet, 16.35~20.5 parts of vitamin micro pill a, amino acid pellet a 35.0~ 44.1 parts, vitamin micro pill b11.4~14.4 part, amino acid pellet b 6.65~10.5, vitamin C micro-pill 12.73~16.0 Part, 5.7~9.36 parts of vitaminAD microballon.Invention proportioning science, reasonable, the stability of product is good, has no toxic side effect, safety Property it is high, there is good biological effect, can apply and prepare treatment Chronic Liver, kidney diaseases drug, alleviate and eliminate movement In training physical fatigue food.
Chinese Patent Application No. 201310055941.0 (ten thousand Hes, CN103142633A) discloses a kind of amino acid glue Capsule (8-11) and preparation method thereof.In particular to it is a kind of include 8 kinds of amino acid and 11 kinds of vitamin micro pills capsule, also It is related to the preparation method of the capsule.The capsule include 7 kinds of microspheric granulas, 7 kinds of microspheric granulas by following parts by weight raw material Composition：2.66~9.9 parts of thiamine mononitrate pellet, 16.35~20.5 parts of vitamin micro pill a, amino acid pellet a 35.0~44.1 Part, 11.4~14.4 parts of vitamin micro pill b, amino acid pellet b 6.65~10.5,12.73~16.0 parts of vitamin C micro-pill, 5.7~9.36 parts of vitaminAD microballon.It is believed that the invention matches, science, reasonable, the stability of product is good, has no toxic side effect, and pacifies Quan Xinggao has good biological effect, can apply and prepare treatment Chronic Liver, kidney diaseases drug, alleviate and eliminate fortune In dynamic training physical fatigue food.It is believed that the invention capsule has the characteristics that be better than the prior art.
Regrettably, the above-mentioned prior art is when preparing the preparation comprising 8 kinds of amino acid and 11 kinds of vitamin Piller is made in amino acid and/or vitamin, is then coated, then coated pellets are divided in empty hard softgel shell. This preparation process has notable higher production cost than it in the encapsulated technique of conventional powder/granule, this to be produced into This will be that patient person's medication brings huge medical burden.
Therefore, develop it is a kind of meet the drug standards require and simple production process comprising 8 kinds of amino acid and 11 kinds dimension The compound amino acid capsule of raw element is that those skilled in the art extremely expect.
Invention content
The present invention goal of the invention be to provide a kind of capsule containing 8 kinds of amino acid and 11 kinds of vitamins, expect this Kind capsule has the characteristics that simple production process and has excellent pharmacy quality.The present invention it has been unexpectedly discovered that It is fully able to realize above-mentioned mesh using the capsule containing 8 kinds of amino acid and 11 kinds of vitamins that the method for the present invention is prepared 's.It finds and is accomplished the present invention is based on this.
In the present invention, the capsule refers to hard capsule well known to art of pharmacy, usual to be different from people The soft capsule known.Hard capsule includes typically capsule shells (also commonly referred to as Capsules) and is wrapped in the capsule Filler in shell, the filler is usually in powder or graininess, wherein adding comprising active constituents of medicine and when necessary Pharmaceutic adjuvant.Known in pharmaceutical field technical staff, for capsule especially hard capsule, inside capsule shells are filled upper Filler is stated, also known as " content ".In upper and lower each embodiment of text of the invention, the various fillers being prepared are filled into Suitable in the Capsules of size, making the content be filled substantially with capsule body, then capsule cap fitting is sealed.
In the first aspect of the present invention, a kind of capsule is provided comprising capsule shells and be wrapped in the capsule shells And it is in powder or granular filler；The capsule shells be using gelatin as gelatin hollow capsule made of key component, it is described Filler includes active material and pharmaceutic adjuvant；The active material includes：
Capsule according to the present invention, each grain include that the amount of active material is：
L-Leu 14.5~22mg L-Isoleucine 4.5~7mg
L-Lysine hydrochloride 20~30mg L-phenylalanine 4~6mg
L-threonine 3.3~5mg Valine 5.3~8mg
L-Trp 4~6mg Methionine (for example, L-Methionine or DL- METHIONINE) 14.5~22mg
Vitamin A 1600~2400IU Calciferol 160~240IU
Vitamin B1 (or sulfuric acid thiamine) 4~6mg Vitamin B2 2.4~3.6mg
Niacinamide 1.6~25mg Vitamin B6 2~3mg
Folic acid 0.16~0.24mg Calcium pantothenate 4~6mg
Vitamin B12 0.8~1.2ug Vitamin C 16~24mg
Vitamin E 0.8~1.2mg 5- hydroxyl anthranilic acid hydrochlorides 0.16~0.24mg
Capsule according to the present invention, each grain include that the amount of active material is：
L-Leu 16.5~20mg L-Isoleucine 5.3~6.5mg
L-Lysine hydrochloride 22.5~27.5mg L-phenylalanine 4.5~5.5mg
L-threonine 3.7~4.6mg Valine 6~7.5mg
L-Trp 4.5~5.5mg Methionine (for example, L-Methionine or DL- METHIONINE) 16.5~20mg
Vitamin A 1800~2200IU Calciferol 180~220IU
Vitamin B1 (or sulfuric acid thiamine) 4.5~5.5mg Vitamin B2 2.7~3.3mg
Niacinamide 1.8~22mg Vitamin B6 2.25~2.75mg
Folic acid 0.18~0.22mg Calcium pantothenate 4.5~5.5mg
Vitamin B12 0.9~1.1ug Vitamin C 18~22mg
Vitamin E 0.9~1.1mg 5- hydroxyl anthranilic acid hydrochlorides 0.18~0.22mg
Capsule according to the present invention, each grain include that the amount of active material is about：
L-Leu 18.3mg L-Isoleucine 5.9mg
L-Lysine hydrochloride 25mg L-phenylalanine 5mg
L-threonine 4.2mg Valine 6.7mg
L-Trp 5mg Methionine (for example, L-Methionine or DL- METHIONINE) 18.4mg
Vitamin A 2000IU Calciferol 200IU
Vitamin B1 (or sulfuric acid thiamine) 5mg Vitamin B2 3mg
Niacinamide 2mg (or 20mg) Vitamin B6 2.5mg
Folic acid 0.2mg Calcium pantothenate 5mg
Vitamin B12 1ug Vitamin C 20mg
Vitamin E 1mg 5- hydroxyl anthranilic acid hydrochlorides 0.2mg
Capsule according to the present invention, wherein the pharmaceutic adjuvant is selected from following one or more：Lactose, shallow lake Powder, microcrystalline cellulose, dextrin, sucrose, silicea, hydroxypropyl methyl cellulose, carboxymethyl starch, sodium carboxymethyl starch, methyl are fine Tie up element, ethyl cellulose etc..
Capsule according to the present invention, the pharmaceutic adjuvant total amount for including in each grain are 80~400mg.
Capsule according to the present invention, the pharmaceutic adjuvant total amount for including in each grain are 100~350mg.
Capsule according to the present invention, the pharmaceutic adjuvant total amount for including in each grain are 100~300mg.
Capsule according to the present invention, wherein the pharmaceutic adjuvant includes：Starch and silicea.
Capsule according to the present invention, wherein the silicea is the pharmaceutic adjuvant containing element silicon.Such as it is selected from dioxy SiClx, colloidal silicon dioxide, talcum powder etc..As Chinese Pharmacopoeia version four in 2015 is recorded, silica and colloidal silica Silicon is two different substances.Colloidal silicon dioxide is also known as superfine silica gel powder.
Capsule according to the present invention, the amount of starch for including in each grain are 80~350mg.
Capsule according to the present invention, the amount of starch for including in each grain are 100~300mg.
Capsule according to the present invention, the amount of starch for including in each grain are 100~250mg.
Capsule according to the present invention, the silicea for including in each grain account for the 0.2~10% of the filler weight.
Capsule according to the present invention, the silicea for including in each grain account for the 0.5~5% of the filler weight.
Capsule according to the present invention, the silicea for including in each grain account for the 0.5~3% of the filler weight.
The weight of capsule according to the present invention, the filler for including in each grain is 200~500mg.
The weight of capsule according to the present invention, the filler for including in each grain is 225~450mg.
The weight of capsule according to the present invention, the filler for including in each grain is 250~400mg.
The granularity of capsule according to the present invention, filler is：99% or more particle can be sieved by 20 mesh.
The granularity of capsule according to the present invention, filler is：99% or more particle can be sieved by 24 mesh.
The granularity of capsule according to the present invention, filler is：95% or more particle can be sieved by 50 mesh.
The granularity of capsule according to the present invention, filler is：90% or more particle can be sieved by 65 mesh.
Capsule according to the present invention, is prepared by method comprising the following steps：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Each material of the present invention can be uniformly mixed by well-mixed technique.Certainly, in order to improve mixing efficiency, also It can be by the small several components of dosage, such as vitamin A, calciferol, folic acid, vitamin B12, vitamin E, 5- hydroxyl neighbour's phenalgins Carboxylic acid hydrochloride etc. is suspended with ethyl alcohol, then is sprayed in all or part of rest activity substance and/or pharmaceutic adjuvant, to be removed After solvent, it is uniformly mixed with the active material of surplus and/or pharmaceutic adjuvant.The present inventor is by verifying discovery, different mixing Method in addition to mixture homogeneity in timeliness it is variant other than, when in every capsule various contents less than/be equal to 5mg activity When substance reaches calculating formula A+1.45S≤15.0 (two annex XE institutes support methods of Chinese Pharmacopoeia version in 2010) of uniformity of dosage units (hereafter whole capsules made from each embodiment, wherein the active material that various contents are less than/are equal to 5mg is computed their A + 1.45S is in 6.2~12.5 ranges), capsule made from these different mixing modes is detected in stability test of the present invention In do not show difference, i.e., different mixing modes to the stability of product and have no significant effect.
Further, second aspect of the present invention provides the method for preparing capsule, the capsule include capsule shells with And it is wrapped in the capsule shells and is in powder or granular filler；The capsule shells are using gelatin as made of key component Gelatin hollow capsule, the filler include active material and pharmaceutic adjuvant；The active material includes：
L-Leu L-Isoleucine
L-Lysine hydrochloride L-phenylalanine
L-threonine Valine
L-Trp Methionine (for example, L-Methionine or DL- METHIONINE)
Vitamin A Calciferol
Vitamin B1 (or sulfuric acid thiamine) Vitamin B2
Niacinamide Vitamin B6
Folic acid Calcium pantothenate
Vitamin B12 Vitamin C
Vitamin E 5- hydroxyl anthranilic acid hydrochlorides；
This approach includes the following steps：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
According to the method for the present invention, each grain of the capsule includes that the amount of active material is：
L-Leu 14.5~22mg L-Isoleucine 4.5~7mg
L-Lysine hydrochloride 20~30mg L-phenylalanine 4~6mg
L-threonine 3.3~5mg Valine 5.3~8mg
L-Trp 4~6mg Methionine (for example, L-Methionine or DL- METHIONINE) 14.5~22mg
Vitamin A 1600~2400IU Calciferol 160~240IU
Vitamin B1 (or sulfuric acid thiamine) 4~6mg Vitamin B2 2.4~3.6mg
Niacinamide 1.6~25mg Vitamin B6 2~3mg
Folic acid 0.16~0.24mg Calcium pantothenate 4~6mg
Vitamin B12 0.8~1.2ug Vitamin C 16~24mg
Vitamin E 0.8~1.2mg 5- hydroxyl anthranilic acid hydrochlorides 0.16~0.24mg
According to the method for the present invention, each grain of the capsule includes that the amount of active material is：
L-Leu 16.5~20mg L-Isoleucine 5.3~6.5mg
L-Lysine hydrochloride 22.5~27.5mg L-phenylalanine 4.5~5.5mg
L-threonine 3.7~4.6mg Valine 6~7.5mg
L-Trp 4.5~5.5mg Methionine (for example, L-Methionine or DL- METHIONINE) 16.5~20mg
Vitamin A 1800~2200IU Calciferol 180~220IU
Vitamin B1 (or sulfuric acid thiamine) 4.5~5.5mg Vitamin B2 2.7~3.3mg
Niacinamide 1.8~22mg Vitamin B6 2.25~2.75mg
Folic acid 0.18~0.22mg Calcium pantothenate 4.5~5.5mg
Vitamin B12 0.9~1.1ug Vitamin C 18~22mg
Vitamin E 0.9~1.1mg 5- hydroxyl anthranilic acid hydrochlorides 0.18~0.22mg
According to the method for the present invention, each grain of the capsule includes that the amount of active material is about：
L-Leu 18.3mg L-Isoleucine 5.9mg
L-Lysine hydrochloride 25mg L-phenylalanine 5mg
L-threonine 4.2mg Valine 6.7mg
L-Trp 5mg Methionine (for example, L-Methionine or DL- METHIONINE) 18.4mg
Vitamin A 2000IU Calciferol 200IU
Vitamin B1 (or sulfuric acid thiamine) 5mg Vitamin B2 3mg
Niacinamide 2mg (or 20mg) Vitamin B6 2.5mg
Folic acid 0.2mg Calcium pantothenate 5mg
Vitamin B12 1ug Vitamin C 20mg
Vitamin E 1mg 5- hydroxyl anthranilic acid hydrochlorides 0.2mg
According to the method for the present invention, wherein the pharmaceutic adjuvant is selected from following one or more：Lactose, starch, Microcrystalline cellulose, dextrin, sucrose, silicea, hydroxypropyl methyl cellulose, carboxymethyl starch, sodium carboxymethyl starch, Methyl cellulose Element, ethyl cellulose etc..
According to the method for the present invention, the pharmaceutic adjuvant total amount for including in each grain of the capsule is 80~400mg.
According to the method for the present invention, the pharmaceutic adjuvant total amount for including in each grain of the capsule is 100~350mg.
According to the method for the present invention, the pharmaceutic adjuvant total amount for including in each grain of the capsule is 100~300mg.
According to the method for the present invention, the pharmaceutic adjuvant described in the capsule includes：Starch and silicea.
According to the method for the present invention, the amount of starch for including in each grain of the capsule is 80~350mg.
According to the method for the present invention, the amount of starch for including in each grain of the capsule is 100~300mg.
According to the method for the present invention, the amount of starch for including in each grain of the capsule is 100~250mg.
According to the method for the present invention, the silicea for including in each grain of the capsule account for the filler weight 0.2~ 10%.
According to the method for the present invention, the silicea for including in each grain of the capsule account for the filler weight 0.5~ 5%.
According to the method for the present invention, the silicea for including in each grain of the capsule account for the filler weight 0.5~ 3%.
According to the method for the present invention, the weight for the filler for including in each grain of the capsule is 200~500mg.
According to the method for the present invention, the weight for the filler for including in each grain of the capsule is 225~450mg.
According to the method for the present invention, the weight for the filler for including in each grain of the capsule is 250~400mg.
According to the method for the present invention, the granularity of the capsule filler is：99% or more particle can be sieved by 20 mesh.
According to the method for the present invention, the granularity of the capsule filler is：99% or more particle can be sieved by 24 mesh.
According to the method for the present invention, the granularity of the capsule filler is：95% or more particle can be sieved by 50 mesh.
According to the method for the present invention, the granularity of the capsule filler is：90% or more particle can be sieved by 65 mesh.
According to the method for the present invention, wherein vitamin A, calciferol, folic acid, vitamin B12, vitamin E, 5- hydroxyls are adjacent Aminobenzoic Acid hydrochloride etc. is suspended with ethyl alcohol and is sprayed to all or part of rest activity substance and/or pharmaceutic adjuvant again In, it after solvent to be removed, is uniformly mixed with the active material of surplus and/or pharmaceutic adjuvant, mixed powder eventually is made.
Gelatin hollow capsule of the present invention has typically been recorded to version in 2010《Chinese Pharmacopoeia》Two, and have perhaps Multi-product is ratified to list by state food pharmaceuticals administration general bureau, such as Chinese medicines quasi-word F20020009 (Shaoxing Renhe), The gelatin hollow capsule of Chinese medicines quasi-word F20020035 (life of Zhejiang enlightening) and Chinese medicines quasi-word F20030004 (the long standing grain in Jiangsu).
Capsule according to the present invention is that the directly encapsulated mode of powder is prepared.
8 kinds of amino acid of one kind of the invention and 11 kinds of vitamin micro pill capsules are preparing treatment Chronic Liver, kidney diaseases drug, delay Application in solution and elimination training physical fatigue food.
In the case of chronic hepatic diseases, it can be effectively improved on the basis of not increasing patient's nitrogen matter and draining burden Cell promotes the 8 kinds of amino acid and 11 kinds of vitamine capsule techniques of the biosynthesis of protein to the bioavailability of amino acid Unique, the technologically advanced, term of validity is more than 3 years, and product of the present invention is used for Chronic Liver, kidney and other disease treatments, alleviates and eliminates Physical fatigue.
The present invention has protrusion excellent as the enteral nutrition preparation for improving nitrogen source amino acid composition in chronic disease therapy Gesture.First, it haves no need to change the dietary structure and other treatment schemes of patient, it will be able to significantly improve the amino acid of patient With protein metabolism；Secondly, in the case of chronic hepatic diseases, it can be on the basis for not increasing patient's nitrogen matter excretion burden On effectively improve bioavailability of the cell to amino acid, promote the biosynthesis of protein.The present invention and existing amino acid Product technology compares, and has the following advantages that：
1. proportioning is reasonable, science, there is good biological effect.Its different and general amino acid preparation, 8 kinds must It needs the ratio of amino acid to combine Asian-Pacific area dietary protein structure, amino acid composition and absorption of human body many factors synthesis to examine Consider and determine, wherein the large percentage of branched-chain amino acid, lysine, methionine, while adding 11 kinds of vitamins, gives full play to amino The synergistic effect of acid and vitamin makes amino acid is balanced in human body to absorb, ensures the bioavailability of amino acid.
2. technique is unique, advanced, solve the disadvantage that other Moriamin Forte preparations, by 8 kinds of essential amino acids and 11 kinds Between can guarantee each ingredient chemical reaction and degradation will not occur in storage period for vitamin mixing, improve various work in product The stability of property ingredient.
3. convenient oral.Moriamin Forte preparation is in the treatment that patients with chronic diseases needs amino acid preparation for a long time, energy Enough make up certain deficiencies of amino acid transfusion.The present invention is particularly suited for the chronic of Long-term taking medicine, both alleviates patient Financial burden, while the psychological bearing capability of patient is improved again.
The capsule that various embodiments of the present invention are prepared, keeps sample for a long time at ambient temperature, respectively at 0,3,6,9, 12, it samples within 18,24,36 months, by hereafter contained method, in conjunction with the assay method of two records of version Chinese Pharmacopoeia in 2010, to not Sample with the time is measured indices.The results show that 0 month sample to keep sample to 36 months of various embodiments of the present invention, 8 kinds of ammonia The content of base acid was respectively maintained within 3 years periods in 94~105% ranges of labelled amount, the content of 11 kinds of vitamin It was respectively maintained in 95~103% ranges of labelled amount within 3 years periods, shows that capsule of the present invention fully meets medicine The requirement of quality standard.
Specific implementation mode
The following examples are used for further illustrating the present invention, but this does not imply that any limitation of the invention. In following experiment, when preparing capsule of the present invention, prepared per the batch of at least 20,000 in terms of capsule number amounts of batch, but It is to be indicated with every amount when listing formula.In following experiment, when preparing capsule of the present invention, in addition do not say such as Bright, the granularity of capsule filler is：95% or more particle can be sieved by 50 mesh.In following experiment, the present invention is prepared When capsule, if not otherwise indicated, Capsules used are gelatin hollow capsules.
Embodiment 1：Prepare capsule
Formula：
L-Leu 18.3mg L-Isoleucine 5.9mg
L-Lysine hydrochloride 25mg L-phenylalanine 5mg
L-threonine 4.2mg Valine 6.7mg
L-Trp 5mg DL- METHIONINE 18.4mg
Vitamin A 2000IU Calciferol 200IU
Vitamin B1 5mg Vitamin B2 3mg
Niacinamide 2mg Vitamin B6 2.5mg
Folic acid 0.2mg Calcium pantothenate 5mg
Vitamin B12 1ug Vitamin C 20mg
Vitamin E 1mg 5- hydroxyl anthranilic acid hydrochlorides 0.2mg
Starch 170mg Silica * 2%
Note：* silicea (silica) is fed intake with the percentage of capsule filling total weight, similarly hereinafter.
Preparation method 1：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Preparation method 2：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) by vitamin A, calciferol, folic acid, vitamin B12, vitamin E, 5- hydroxyl anthranilic acid hydrochlorides Six are sprayed to ethyl alcohol (dosage is 3 times of this 6 kinds of active material total weights) suspension in the starch of 1/3 amount again, to be dried to remove It after removing solvent, is uniformly mixed with the active material of surplus and/or pharmaceutic adjuvant, mixed powder eventually is made；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Two batches capsule is made by both the above method.It is when hereafter involved in each test example to 1 sample of embodiment Refer to 1 gained capsule of preparation method or is prepared according to preparation method 1；But in each test example 2 two kinds of capsules of preparation method 1 and preparation method without Notable difference.
The gelatin hollow capsule that the present embodiment uses is F20020009, when being hereafter not indicated otherwise, also uses the hollow glue Capsule.
Embodiment 2：Prepare capsule
Formula：
L-Leu 18.3mg L-Isoleucine 5.9mg
L-Lysine hydrochloride 25mg L-phenylalanine 5mg
L-threonine 4.2mg Valine 6.7mg
L-Trp 5mg L-Methionine 18.4mg
Vitamin A 2000IU Calciferol 200IU
Sulfuric acid thiamine 5mg Vitamin B2 3mg
Niacinamide 20mg Vitamin B6 2.5mg
Folic acid 0.2mg Calcium pantothenate 5mg
Vitamin B12 1ug Vitamin C 20mg
Vitamin E 1mg 5- hydroxyl anthranilic acid hydrochlorides 0.2mg
Starch 180mg Silica 2%
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually, (its granularity is：90% or more particle can be sieved by 65 mesh)；
(iii) mixed powder eventually is filled into hard capsule case (F20020035), capsule body and capsule cap is set with, sealing, To obtain the final product.
Embodiment 3：Prepare capsule
Formula：
L-Leu 14.5mg L-Isoleucine 4.5mg
L-Lysine hydrochloride 30mg L-phenylalanine 6mg
L-threonine 3.3mg Valine 5.3mg
L-Trp 6mg DL- METHIONINE 22mg
Vitamin A 1600IU Calciferol 160IU
Vitamin B1 6mg Vitamin B2 2.4mg
Niacinamide 1.6mg Vitamin B6 3mg
Folic acid 0.24mg Calcium pantothenate 4mg
Vitamin B12 0.8ug Vitamin C 24mg
Vitamin E 1.2mg 5- hydroxyl anthranilic acid hydrochlorides 0.16mg
Starch 100mg Silica 5%
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually, (its granularity is：95% or more particle can be sieved by 65 mesh)；
(iii) mixed powder eventually is filled into hard capsule case (F20030004), capsule body and capsule cap is set with, sealing, To obtain the final product.
Embodiment 4：Prepare capsule
Formula：
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Embodiment 5：Prepare capsule
Formula：
L-Leu 16.5mg L-Isoleucine 5.3mg
L-Lysine hydrochloride 27.5mg L-phenylalanine 5.5mg
L-threonine 3.7mg Valine 6mg
L-Trp 5.5mg DL- METHIONINE 20mg
Vitamin A 1800IU Calciferol 180IU
Vitamin B1 5.5mg Vitamin B2 3.3mg
Niacinamide 1.8mg Vitamin B6 2.25mg
Folic acid 0.22mg Calcium pantothenate 5.5mg
Vitamin B12 0.9ug Vitamin C 18mg
Vitamin E 1.1mg 5- hydroxyl anthranilic acid hydrochlorides 0.22mg
Starch 250mg Silica 5%
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Embodiment 6：Prepare capsule
Formula：
L-Leu 20mg L-Isoleucine 6.5mg
L-Lysine hydrochloride 22.5mg L-phenylalanine 4.5mg
L-threonine 4.6mg Valine 7.5mg
L-Trp 4.5mg DL- METHIONINE 16.5mg
Vitamin A 2200IU Calciferol 220IU
Vitamin B1 4.5mg Vitamin B2 2.7mg
Niacinamide 2.2mg Vitamin B6 2.75mg
Folic acid 0.18mg Calcium pantothenate 4.5mg
Vitamin B12 1.1ug Vitamin C 22mg
Vitamin E 0.9mg 5- hydroxyl anthranilic acid hydrochlorides 0.18mg
Starch 150mg Silica 10%
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Embodiment 7：Prepare capsule
Formula：
L-Leu 14.5mg L-Isoleucine 7mg
L-Lysine hydrochloride 30mg L-phenylalanine 4mg
L-threonine 3.3mg Valine 8mg
L-Trp 6mg L-Methionine 14.5mg
Vitamin A 1600IU Calciferol 240IU
Sulfuric acid thiamine 6mg Vitamin B2 2.4mg
Niacinamide 16mg Vitamin B6 3mg
Folic acid 0.24mg Calcium pantothenate 4mg
Vitamin B12 0.8ug Vitamin C 24mg
Vitamin E 1.2mg 5- hydroxyl anthranilic acid hydrochlorides 0.16mg
Starch 150mg Silica 0.5%
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Embodiment 8：Prepare capsule
Formula：
L-Leu 22mg L-Isoleucine 4.5mg
L-Lysine hydrochloride 20mg L-phenylalanine 6mg
L-threonine 5mg Valine 5.3mg
L-Trp 4mg L-Methionine 22mg
Vitamin A 2400IU Calciferol 160IU
Sulfuric acid thiamine 4mg Vitamin B2 3.6mg
Niacinamide 25mg Vitamin B6 2mg
Folic acid 0.16mg Calcium pantothenate 6mg
Vitamin B12 1.2ug Vitamin C 16mg
Vitamin E 0.8mg 5- hydroxyl anthranilic acid hydrochlorides 0.24mg
Starch 180mg Silica 3%
Preparation method：It is prepared according to 1 preparation method 2 of embodiment.
Embodiment 9：Prepare capsule
Formula：
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Embodiment 10：Prepare capsule
Formula：
L-Leu 16.5mg L-Isoleucine 6.5mg
L-Lysine hydrochloride 27.5mg L-phenylalanine 4.5mg
L-threonine 3.7mg Valine 7.5mg
L-Trp 5.5mg L-Methionine 16.5mg
Vitamin A 1800IU Calciferol 220IU
Sulfuric acid thiamine 5.5mg Vitamin B2 2.7mg
Niacinamide 18mg Vitamin B6 2.75mg
Folic acid 0.22mg Calcium pantothenate 4.5mg
Vitamin B12 0.9ug Vitamin C 22mg
Vitamin E 1.1mg 5- hydroxyl anthranilic acid hydrochlorides 0.18mg
Starch 150mg Silica 1%
Preparation method：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
Embodiment 11：Prepare capsule
It respectively refers to the formula of embodiment 1-10 and preparation method prepares capsule, different is only to replace with silicea therein Colloidal silicon dioxide (embodiment 1 is prepared according to preparation method 1).
Embodiment 12：Prepare capsule
It respectively refers to the formula of embodiment 1-10 and preparation method prepares capsule, different is only to replace with silicea therein Talcum powder (embodiment 1 is prepared according to preparation method 1).
Test example 1：The general aspects of capsule is investigated
Whole capsules (filler is usually also known as content in this field) made from foregoing embodiments 1-12 carry out It investigates
1、【Differentiate】
(1) capsule 1 is taken, water 10ml is added, makes dissolving, is filtered, filtrate adds ninhydrin solution 2ml, heating water bath, solution Aobvious purple.After testing, above-mentioned testing result is presented in whole capsule samples.
(2) in the chromatography recorded under assay item, the retention time at various amino acid peaks should be to each corresponding reference substance Retention time it is consistent.After testing, above-mentioned testing result is presented in whole capsule samples.
(3) in the chromatography recorded under assay item, the retention time at various vitamin peaks should be to each corresponding reference substance Retention time it is consistent.After testing, above-mentioned testing result is presented in whole capsule samples.
(4) it takes the fine powder of this product appropriate (being approximately equivalent to pangamic acid mg), adds sodium hydroxide test solution 2.5ml, the potassium ferricyanide Test solution 0.5ml and n-butanol 5ml, strength shaking 2 minutes, placement makes layering, upper layer alcohol liquid show strong blue-fluorescence, and acid adding makes At acidity, fluorescence disappears, then alkali is added to make into alkalinity, and fluorescence shows again.After testing, above-mentioned inspection is presented in whole capsule samples Survey result.
(5) it takes the fine powder of this product appropriate (being approximately equivalent to vitamin B2 1mg), adds water 100ml, shake, solution is in transmitted light Lower observation shows pistac and has yellow-green fluorescence, and mine acid or aqueous slkali, fluorescence is added to disappear.After testing, whole capsule examinations Above-mentioned testing result is presented in sample.
(6) take Capsule content about 2.0g, add water 15ml, boil, let cool, the translucent gel of off-white color Object；The gelling material about 1ml is taken, iodine test solution 1 is added to drip, that is, shows blue, black-and-blue or atropurpureus, gradually fades after heating.We Method be check in preparation whether the classical way containing starch, through with amino acid-vitamin mixed-powder ratio for being not added with starch Compared with or with compared with being not added with the mixed-powder of amino acid-vitamin this method be still reliable, other each groups in prescription Dividing does not influence starch coloration judgement.After testing, above-mentioned testing result is presented in whole capsule samples.
(7) qualitative/quantitative of silicea：(thank to Xinhua etc., the survey of talcum powder content in different food products with reference to thanking to Xinhua's document It is fixed, Henan preventive medicine magazine, 2011,22 (1):20) method in measures the content of talcum powder in Capsule content；With And reference Zhang Yaoli documents (Zhang Yaoli etc., the assay method of Surinam's timber dioxide-containing silica, forestry science and technology exploitation, 2002,16 (4):15) method in measures the content of silica in Capsule content.It is measured with both the above known method The capsule sample for being all added to silicea show containing talcum powder or silica, and after measured, silicon wherein included The amount of agent and the inventory of silicea in involved capsule are coincide.In addition, with reference to the four " dioxies recorded of version Chinese Pharmacopoeia in 2015 Discrimination method in SiClx " and " colloidal silicon dioxide ", can also be easy and accurately to the silicea in Capsule content into Row Qualitive test.
(8) the qualitative determination of main material gelatin used in Capsules：It, can for the gelatin hollow capsule that the present invention uses Discrimination method in " gelatinum pro capsulae " that is recorded with reference to version Chinese Pharmacopoeia four in 2015, is readily determined Capsules used Whether shell is made of with gelatin for main material system.
2、【It checks】
(1) loss on drying：This product 10 is taken, content is poured out, after mixing, takes about 1g, it is 1 hour dry at 105 DEG C, Less loss weight must not cross 4%.(two annex VIII L of Chinese Pharmacopoeia version in 2010).
After testing, whole capsule sample less loss weight are respectively less than 2.6%.
Other inspection items of capsule can refer to related under two annex of Chinese Pharmacopoeia version in 2010, I E capsule agent item Items regulation carries out, and all capsule testing result meets the general provision of pharmacopeia.
3、【Assay】
(1) amino acid
Content uniformity inspection is carried out to capsule；This product content under content uniformity item is taken, mixing is finely ground, and precision claims It takes in right amount, with water dissolution and dilutes a certain concentration, filter, take subsequent filtrate as test solution, with amino acid analysis appropriate Instrument or high performance liquid chromatograph separation determination；Corresponding amino acid reference substance is separately taken, the reference substance solution of respective concentration is made, together Method measures；By external standard method with the content of each amino acid of calculated by peak area.
(2) vitamin C, niacinamide, vitamin B1, vitamin B6
It is measured according to high performance liquid chromatography (two annex V D of Chinese Pharmacopoeia version in 2010)；
Chromatographic condition and system suitability：It is filler with octadecylsilane chemically bonded silica；It is flowing with acetonitrile Phase A, 0.04% pentanesulfonic acid sodium solution (glacial acetic acid for containing 0.4%) is Mobile phase B, and the regulation according to the form below carries out gradient and washes It is de-；Flow velocity 1.0ml/min, Detection wavelength 275nm, 25 DEG C of column temperature；Number of theoretical plate should be not less than by the calculating of vitamin C peak 2000；
Time (minute) Mobile phase A (%) Mobile phase B (%)
- 10~0 4 96
0~8 4 96
9~15 10 90
16~27 13 87
Measuring method：This product content under content uniformity item is taken, finely ground, precision weighs appropriate (amount for being approximately equivalent to 1) It sets in 100ml measuring bottles, 0.01mol/L hydrochloric acid solutions (metaphosphoric acid for containing 0.1%) about 80ml is added, is ultrasonically treated 30 minutes, puts It is cold, it is diluted to scale, is shaken up, is filtered；Precision measures 10 μ l of subsequent filtrate and injects liquid chromatograph, records chromatogram；It is another that dimension is taken to give birth to Plain C, vitamin B1, vitamin B6 and niacinamide reference substance are appropriate, accurately weighed, (contain 0.1% with 0.01mol/L hydrochloric acid solutions Metaphosphoric acid) dissolve and quantify dilution and be made in every 1ml that the mixing containing 0.2mg, 0.05mg, 0.025mg and 0.02mg is molten respectively Liquid, product solution (interim brand-new), is measured in the same method as a contrast；By external standard method with calculated by peak area to get.
(3) vitamin B2
It is measured according to high performance liquid chromatography (two annex V D of Chinese Pharmacopoeia version in 2010)；
Chromatographic condition and system suitability：It is filler with octadecylsilane chemically bonded silica；With acetonitrile -0.04% Pentanesulfonic acid sodium solution (contain 0.4% glacial acetic acid) (13: 87) be mobile phase, flow velocity 1.0ml/min, Detection wavelength is 267nm, 25 DEG C of column temperature；Number of theoretical plate is calculated by vitamin B2 peak should be not less than 2000；
Measuring method：It is protected from light operation；This product content under content uniformity item is taken, finely ground, precision weighs (to be approximately equivalent in right amount 1 amount) it sets in 100ml measuring bottles, 0.01mol/L hydrochloric acid solutions (metaphosphoric acid for containing 0.1%) about 80ml is added, is ultrasonically treated It 10 minutes, sets in water-bath and heats 30 minutes, and constantly shake, let cool, be diluted to scale, filter；Precision measures 10 μ l of subsequent filtrate Liquid chromatograph is injected, chromatogram is recorded；Separately take vitamin B2 reference substance appropriate, it is accurately weighed, with 0.01mol/L hydrochloric acid solutions (metaphosphoric acid for containing 0.1%) heating water bath makes dissolving, lets cool, and quantify the solution for diluting and being made in every 1ml containing about 0.03mg, makees For reference substance solution (interim brand-new), it is measured in the same method.By external standard method with calculated by peak area to get.
(4) calcium pantothenate
It is measured according to high performance liquid chromatography (two annex V D of Chinese Pharmacopoeia version in 2010)；
Chromatographic condition and system suitability：It is filler with octadecylsilane chemically bonded silica；It is flowing with acetonitrile Phase A, 0.1% phosphoric acid solution (v/v) is Mobile phase B, and the regulation according to the form below carries out gradient elution；Flow velocity 1.0ml/min, inspection Survey wavelength is 210nm, and column temperature is 25 DEG C；Number of theoretical plate is calculated by calcium pantothenate peak should be not less than 5000；
Time (minute) Mobile phase A (%) Mobile phase B (%)
- 10~0 3 97
0~22 3 97
23~36 15 85
Measuring method：This product content under content uniformity item is taken, finely ground, precision weighs (is approximately equivalent to calcium pantothenate in right amount The amount of 12.5mg) it sets in 50ml measuring bottles, 0.1% phosphoric acid solution (v/v) about 40ml is added, is ultrasonically treated 20 minutes, lets cool, it is dilute It releases to scale, shakes up, filter；Precision measures 10 μ l of subsequent filtrate and injects liquid chromatograph, records chromatogram；Separately calcium pantothenate is taken to compare Appropriate product, it is accurately weighed, it is dissolved with 0.1% phosphoric acid solution (v/v), and quantify dilution and be made in every 1ml containing about 0.25mg's Solution, product solution, is measured in the same method as a contrast；By external standard method with calculated by peak area to get.
(5) folic acid
It is measured according to high performance liquid chromatography (two annex V D of Chinese Pharmacopoeia version in 2010)；
Chromatographic condition and system suitability：It is filler with octadecylsilane chemically bonded silica；It is flowing with acetonitrile Phase A, 0.05mol/L potassium dihydrogen phosphate (with phosphoric acid tune pH to 3.0 ± 0.2) are Mobile phase B, and the regulation according to the form below carries out Gradient elution；Flow velocity 1.0ml/min, Detection wavelength 280nm, column temperature are 35 DEG C, and number of theoretical plate should not be low by the calculating of folic acid peak In 5000.
Time (minute) Mobile phase A (%) Mobile phase B (%)
0~17 9 91
18~25 15 85
26~30 9 91
Measuring method：It is protected from light operation；This product content under content uniformity item is taken, finely ground, precision weighs (to be approximately equivalent in right amount The amount of folic acid 0.5mg) it sets in 25ml measuring bottles, 0.2% sodium carbonate liquor about 20ml is added, shaking makes to be uniformly dispersed, and places 30 points Clock is ultrasonically treated 30 minutes, lets cool, be diluted to scale, shake up, and filters；Precision measures 10 μ l of subsequent filtrate and injects liquid chromatograph, Record chromatogram；It is another to take folic acid reference substance about 10mg, it is accurately weighed, it sets in 50ml measuring bottles, 0.2% sodium carbonate liquor 10ml is added Make dissolving, is diluted with water to scale, as a contrast product concentrated wiring liquid；Precision measures reference substance concentrated wiring liquid 1.0ml, sets 10ml measuring bottles In, it is diluted with water to scale, the solution containing about 0.02mg in every 1ml is made, as a contrast product solution (interim brand-new), same to method It measures.By external standard method with calculated by peak area to get.
(6) vitamin A, calciferol, vitamin E
It is measured according to high performance liquid chromatography (two annex VD of Chinese Pharmacopoeia version in 2010)；
Chromatographic condition and system suitability：It is filler with octadecylsilane chemically bonded silica；With methanol-water (98: 2) it is mobile phase；Flow velocity is 0.6ml/min, and Detection wavelength 265nm, column temperature is 25 DEG C；Number of theoretical plate respectively press vitamin A, Calciferol, vitamin E peak, which calculate, should be not less than 2000；
Measuring method：It is protected from light operation；This product content under content uniformity item is taken, finely ground, precision weighs (to be approximately equivalent in right amount Dehydroretinol 0000IU, calciferol 2000IU, vitamin E 10.0mg) it sets in 100ml conical flask with cover, 25ml is added in precision N-hexane, weighed weight are set in ice bath and are ultrasonically treated 30 minutes, take out, then weighed weight, less loss weight is supplied with n-hexane, It shakes up, filters, precision measures subsequent filtrate 10ml, is dried up with nitrogen, and residue isopropanol dissolves and be settled to 10ml, shakes up, filter It crosses, precision measures 10 μ l of subsequent filtrate and injects liquid chromatograph, records chromatogram；Separately take vitamine A acetate, calciferol and dimension Raw element E reference substances are appropriate, accurately weighed, dissolve with isopropanol and quantify dilution be made in every 1ml respectively containing 0.3mg, 2 μ g and The mixed solution of 0.5mg, product solution, is measured in the same method as a contrast.By external standard method with calculated by peak area to get.
(7) 5- hydroxyls anthranilic acid
It is measured according to high performance liquid chromatography (two annex V D of Chinese Pharmacopoeia version in 2010)；
Chromatographic condition and system suitability：It is filler with octadecylsilane chemically bonded silica；It is flowing with acetonitrile Phase A, 0.05mol/L potassium dihydrogen phosphate (containing 0.04% sodium pentanesulfonate) are Mobile phase B, and the regulation according to the form below carries out ladder Degree elution；Flow velocity 1.0ml/min, Detection wavelength 240nm, column temperature are 25 DEG C；Number of theoretical plate presses 5- hydroxyl anthranilic acids peak 5000 should be not less than by calculating.
Time (minute) Mobile phase A (%) Mobile phase B (%)
0~10 0 100
10~20 20 80
21~30 0 100
Measuring method：This product content under content uniformity item is taken, finely ground, precision weighs (it is adjacent to be approximately equivalent to 5- hydroxyls in right amount Aminobenzoic Acid 0.5mg) it sets in 25ml measuring bottles, 0.01mol/L hydrochloric acid solution about 20ml are added, is ultrasonically treated 30 minutes, lets cool, it is dilute It releases to scale, shakes up, filter；Precision measures 10 μ l of subsequent filtrate and injects liquid chromatograph, records chromatogram；Separately take 5- hydroxyl neighbour's ammonia Benzoic acid reference substance is appropriate, accurately weighed, makes dissolving with 0.01mol/L hydrochloric acid solutions, and quantify dilution be made in every 1ml containing about The solution of 0.02mg, product solution, is measured in the same method as a contrast.By external standard method with calculated by peak area to get.
Each capsule being prepared as above is according to above-mentioned【Assay】Method is detected, 8 kinds of amino acid and the life of various dimensions Element measurement result active component corresponding to capsule theoretical inventory coincide, its respectively theory inventory 95~ In 105% range.
Test example 2：The study on the stability of capsule
The capsule dispensed with gelatin hollow capsule being prepared as above is respectively placed in seal-packed aluminum-plastic composite membrane bag In, it is placed under 40 °C of constant temperatures and places June, various amino acid and dimension life in each capsule when measuring 0 month respectively with June The content of element.For the same amino acid or vitamin in same a collection of capsule, examination below calculates the residual of the active constituent Remaining content (%)：
Residual content (%)=(0 month content of content ÷ in June) × 100%
Above-described embodiment 1 to embodiment 12 various capsules, after measured：
Their leucine, isoleucine, lysine, methionine, valine, threonine, phenylalanine are at June Residual content be all higher than 94%, in 94~99% ranges, comply fully with general requirements for pharmaceuticals residual content be more than 90% Regulation；
Their vitamin A, calciferol, vitamin B1, vitamin B2, niacinamide, vitamin B6, folic acid, calcium pantothenate, The residual content of vitamin E, 5- hydroxyls anthranilic acid at June is all higher than 93%, complete in 93~98% ranges Meet the regulation that general requirements for pharmaceuticals residual content is more than 90% entirely；
The residual content of both the vitamin Cs of various capsules, tryptophan at June respectively in 93~97% ranges and In 93~95% ranges.
Test example 21：
The content of ten kinds of capsules of above-described embodiment 1 to embodiment 10 is taken out from capsule shells and directly uses vial Packing either directly uses the packing of aluminum plastic compound membrane bag or with hydroxypropyl methylcellulose Capsules (Chinese medicines quasi-word F20090002 it) dispenses, either with algal polysaccharides Capsules (Chinese medicines quasi-word F20050002) packing or with the hollow glue of pectin Packing (is made) in capsule according to 200910185990.X specifications 1 methods of embodiment of page 2, or with carboxymethyl cellulose Capsules (being made according to 200910116242.6 specification, 1 methods of embodiment of page 3) packing.Ten kinds of capsules are measured according to 2 the method for test example Agent content powder stability in this 6 kinds of inner packings being in direct contact with drug.
The results show that during whole capsule 's content powder are packed at 6 kinds
Their leucine, isoleucine, lysine, methionine, valine, threonine, phenylalanine and tryptophan Residual content at June is all higher than 94%, and in 94~98% ranges, it is big to comply fully with general requirements for pharmaceuticals residual content In 90% regulation；
Their vitamin A, calciferol, vitamin B1, vitamin B2, niacinamide, vitamin B6, folic acid, calcium pantothenate, This residual content at June of vitamin E, 5- hydroxyls anthranilic acid and vitamin C is all higher than 93%, 93~ In 98% range, the regulation that general requirements for pharmaceuticals residual content is more than 90% is complied fully with；It is not present in gelatine capsule agent The unstable situation of both the vitamin C that occurs when packaging, tryptophans.In addition after measured, made in embodiment 11 and embodiment 12 Each capsule obtained is measured according to 21 method of this test example, they are essentially identical with the result of the capsule of embodiment 1-10.
Test example 22：
Respectively refer to the formula and preparation method of embodiment 1-10, different is only not add starch and silicea, obtain 10 kinds with The capsule of gelatin hollow capsule filling.Leucine, different bright ammonia in 10 kinds of capsules are measured referring next to the method for test example 2 Acid, lysine, methionine, valine, threonine, phenylalanine and vitamin A, calciferol, vitamin B1, dimension life This remnants at June of plain B2, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin E, 5- hydroxyls anthranilic acid As a result content shows that residual content of whole components at June including tryptophan is all higher than 93%, 93~97% In range.The residual content of tryptophan and vitamin C at June is respectively in 75~82% ranges and 83~87% ranges It is interior.
Test example 23：
The formula and preparation method of embodiment 1-10 are respectively referred to, different is only not add starch and silicea, obtains 10 kinds and mixes Powder is closed, respectively uses this 10 kinds of mixed-powders respectively the packing of aluminum plastic compound membrane bag, vial packing, hydroxypropyl methylcellulose empty Heart-soothing capsule or the packing of algal polysaccharides Capsules.Ten kinds of content powder are measured in this 4 kinds and medicine according to 2 the method for test example Stability in the inner packing that product are in direct contact.
The results show that during whole capsule 's content powder are packed at 4 kinds：
Their leucine, isoleucine, lysine, methionine, valine, threonine, phenylalanine, tryptophan Residual content at June is all higher than 93%, and in 93~96% ranges, it is big to comply fully with general requirements for pharmaceuticals residual content In 90% regulation；
Their vitamin A, calciferol, vitamin B1, vitamin B2, niacinamide, vitamin B6, folic acid, calcium pantothenate, This residual content at June of vitamin E, 5- hydroxyls anthranilic acid, vitamin C is all higher than 93%, 93~ In 97% range.
As it can be seen that when not adding starch and silicea, hybrid particles are unstable in gelatin hollow capsule, and in other interior packets It is stable to fill in material.
Test example 24：
The formula and preparation method of embodiment 1-10 are respectively referred to, different is only that vitamin C is not added in prescription, obtains 10 kinds The capsule filled with gelatin hollow capsule.Leucine, different bright ammonia in 10 kinds of capsules are measured referring next to the method for test example 2 Acid, lysine, methionine, valine, threonine, phenylalanine and tryptophan and vitamin A, calciferol, vitamin B1, vitamin B2, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin E, 5- hydroxyls anthranilic acid this at June Residual content, as a result whole components residual content at June of the display including tryptophan be all higher than 93%, 93 In~96% range.In addition after measured, each capsule obtained is surveyed according to 24 method of this test example in embodiment 11 and embodiment 12 Fixed, they are essentially identical with the result of the capsule of embodiment 1-10.
Test example 25：
The formula and preparation method of embodiment 1-10 are respectively referred to, different is only that tryptophan is not added in prescription, obtains 10 kinds The capsule filled with gelatin hollow capsule.Leucine, different bright in 10 kinds of capsules is measured referring next to the method for test example 2 Propylhomoserin, lysine, methionine, valine, threonine, phenylalanine and vitamin A, calciferol, vitamin B1, dimension Raw element B2, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin E, vitamin C, 5- hydroxyls anthranilic acid this 6 As a result residual content when the moon shows that residual content of whole components at June including vitamin C is all higher than 93%, In 93~95% ranges.In addition after measured, each capsule obtained shines this test example 25 in embodiment 11 and embodiment 12 Method measures, they are essentially identical with the result of the capsule of embodiment 1-10.
Test example 26：
Respectively refer to the formula and preparation method of embodiment 1-10, different be only the starch that will wherein use replace with lactose or Microcrystalline cellulose or deduction are not added with starch, obtain 30 kinds of capsules filled with gelatin hollow capsule.Referring next to experiment The method of example 2 measures leucine, isoleucine, lysine, methionine, valine, threonine, phenylpropyl alcohol in this 30 kinds of capsules It is propylhomoserin, tryptophan and vitamin A, calciferol, vitamin B1, vitamin B2, niacinamide, vitamin B6, folic acid, general This residual content at June of sour calcium, vitamin E, vitamin C, 5- hydroxyls anthranilic acid.The results show that in addition to color Outside propylhomoserin and vitamin C, residual content of all other component at June is all higher than 94%, in 94~97% ranges；But Be in this 30 kinds of capsules the residual content of tryptophan and vitamin C at June respectively in 82~86% ranges and In 80~86% ranges.In addition after measured, each capsule obtained shines 26 method of this test example in embodiment 11 and embodiment 12 It measures, they are essentially identical with the result of the capsule of embodiment 1-10.This shows to work as without using starch or is used instead it Its auxiliary material can not achieve the preparation performance of excellent stability when replacing.
Test example 27：
The formula and preparation method of embodiment 1-10 are respectively referred to, different is only that the silicea that will wherein use replaces with three silicic acid Magnesium or aluminium-magnesium silicate or deduction are not added with silicea, obtain 30 kinds of capsules filled with gelatin hollow capsule.Referring next to examination The method for testing example 2 measures leucine, isoleucine, lysine, methionine, valine, threonine, benzene in this 30 kinds of capsules Alanine, tryptophan and vitamin A, calciferol, vitamin B1, vitamin B2, niacinamide, vitamin B6, folic acid, This residual content at June of calcium pantothenate, vitamin E, vitamin C, 5- hydroxyls anthranilic acid.The results show that in addition to Outside tryptophan and vitamin C, residual content of all other component at June is all higher than 93%, in 93~96% ranges； But in this 30 kinds of capsules the residual content of tryptophan and vitamin C at June respectively in 80~83% ranges with And 83~86% in range.This shows when without using silicea or being used instead when other auxiliary materials are replaced and can not achieve good stable The preparation performance of property.
The above test example shows to load the compound amino acid vitamin mixed-powder filled in Capsules, with gelatin In the case of for Capsules material there is taboo in both vitamin C and tryptophan, can overcome these by the method for the invention Taboo.
Test example 28：Prepare capsule
The capsule for including 7 kinds of pellets is made in formula and preparation method according to CN101773512B (ten thousand Hes) embodiment 1, uses gelatin Capsules load.According to the method above with reference to test example 2 measure leucine in this capsule, isoleucine, lysine, Methionine, valine, threonine, phenylalanine, tryptophan and vitamin A, calciferol, vitamin B1, vitamin B2, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin E, vitamin C, 5- hydroxyls anthranilic acid this at June Residual content.The results show that the residual content including tryptophan and ascorbic whole components at June is all higher than 93%, In 93~98% ranges.Although the capsule of this prior art preparation is stable, it require that using extremely multiple Miscellaneous production technology.
Test example 3：The hygroscopicity of capsule 's content powder is investigated
The hygroscopicity of capsule 's content powder is investigated：Capsule 's content powder is placed in vial, opposite January is placed under the conditions of temperature 75%, 25 DEG C of temperature, is weighed to powder before and after disposition, with 1 the end of month increased weight divided by initially The percentage of powder weight is used as weightening percentage (%), and using the weightening percentage (%) as evaluation index.
It has been measured that,
The weightening percentage (%) of whole Capsule content powder of embodiment 1-12 is in 0.3~1.9% range；
The weightening percentage (%) of 22 10 kinds of Capsule content powder of gained of test example is in 8.5~13.6% ranges It is interior；
The weightening percentage (%) of the whole Capsule content powder of 26 gained of test example is in 7.7~13.9% ranges It is interior；
Test example 27 does not have to the weightening percentage of the Capsule content powder (only add starch and be not added with silicea) of silicea Number (%) is in 6.4~11.2% ranges；
The formula and preparation method of embodiment 1 and embodiment 2 are respectively referred to, different is only that the starch that will wherein use replaces with Dextrin, sucrose, hydroxypropyl methyl cellulose, carboxymethyl starch, sodium carboxymethyl starch, methylcellulose or ethyl cellulose, obtain To 14 kinds of capsules, the weightening percentage (%) of content powder is in 7.8~13.1% ranges.
These results indicate that in the case where preparation is directly mixed without preparing piller with powder, amino acid/dimension life It adds starch in cellulose capsule to be advantageous for obtaining the capsule filling with agent of low hygroscopicity, but this effect needs silicon It could be obtained in the presence of agent.
Embodiments of the present invention are not limited to the above embodiments, and that makes without departing from the purpose of the present invention is various Within variation all belongs to the scope of protection of the present invention.

Claims (14)

1. a kind of capsule comprising capsule shells and be wrapped in the capsule shells and be in powder or granular filler；Institute It is using gelatin as gelatin hollow capsule made of key component to state capsule shells, and the filler includes active material and medicinal auxiliary Material；
Active material that each grain of the capsule includes and in an amount of from：
The capsule is that the directly encapsulated mode of powder is prepared；The pharmaceutic adjuvant includes：Starch and silicea, institute It states silicea and is selected from silica, colloidal silicon dioxide, talcum powder；Amount of starch is 100~300mg in each capsule, each Silicea accounts for the 0.2~10% of filler weight in grain capsule.
2. capsule according to claim 1, each grain includes that the amount of active material is：
3. capsule according to claim 1, each grain includes that the amount of active material is：
4. capsule according to claim 1, methionine is L-Methionine or DL- METHIONINE.
5. capsule according to claim 1, the amount of starch for including in each grain is 100~250mg.
6. capsule according to claim 1, the silicea for including in each grain accounts for the 0.5~5% of the filler weight.
7. capsule according to claim 1, the silicea for including in each grain accounts for the 0.5~3% of the filler weight.
8. capsule according to claim 1, the weight for the filler for including in each grain is 200~500mg.
9. capsule according to claim 1, the weight for the filler for including in each grain is 225~450mg.
10. capsule according to claim 1, the weight for the filler for including in each grain is 250~400mg.
11. the granularity of capsule according to claim 1, filler is：95% or more particle can be sieved by 50 mesh.
12. the granularity of capsule according to claim 1, filler is：90% or more particle can be sieved by 65 mesh.
13. according to claim 1 to 12 any one of them capsule, it is prepared by method comprising the following steps 's：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
14. the method for preparing any one of claim 1 to 12 capsule, this approach includes the following steps：
(i) each solid material is respectively crushed into the powder that can be sieved by 65 mesh；
(ii) each material is uniformly mixed, at mixed powder eventually；
(iii) mixed powder eventually is filled into hard capsule case, capsule body and capsule cap is set with, sealing to get.
CN201610060285.7A 2016-01-28 2016-01-28 Compound capsule Active CN105596358B (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1424027A (en) * 2002-12-25 2003-06-18 王颖 Composite amino acid capsule and preparation thereof
CN101773512A (en) * 2010-01-25 2010-07-14 深圳万和制药有限公司 8-amino acid/11-vitamin containing micro granule capsule and preparation method thereof
CN102784147A (en) * 2011-05-19 2012-11-21 金色年华药业有限公司 Compound amino acid vitamin capsule
CN103142633A (en) * 2013-02-22 2013-06-12 深圳万和制药有限公司 Compound amino acid capsule including eight amino acids and eleven vitamins

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070286909A1 (en) * 2006-06-07 2007-12-13 Daniel S. Smith Amino acid compositions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1424027A (en) * 2002-12-25 2003-06-18 王颖 Composite amino acid capsule and preparation thereof
CN101773512A (en) * 2010-01-25 2010-07-14 深圳万和制药有限公司 8-amino acid/11-vitamin containing micro granule capsule and preparation method thereof
CN102784147A (en) * 2011-05-19 2012-11-21 金色年华药业有限公司 Compound amino acid vitamin capsule
CN103142633A (en) * 2013-02-22 2013-06-12 深圳万和制药有限公司 Compound amino acid capsule including eight amino acids and eleven vitamins

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