CN1297280C - Breviscapine amino acid transfusion liquid and its producing method - Google Patents
Breviscapine amino acid transfusion liquid and its producing method Download PDFInfo
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- CN1297280C CN1297280C CNB2003101109662A CN200310110966A CN1297280C CN 1297280 C CN1297280 C CN 1297280C CN B2003101109662 A CNB2003101109662 A CN B2003101109662A CN 200310110966 A CN200310110966 A CN 200310110966A CN 1297280 C CN1297280 C CN 1297280C
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- 229920005549 butyl rubber Polymers 0.000 description 1
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- 239000002738 chelating agent Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
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- 229960001149 dopamine hydrochloride Drugs 0.000 description 1
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- 239000000835 fiber Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
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- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
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- 229960002449 glycine Drugs 0.000 description 1
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- 230000036541 health Effects 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
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- 238000012549 training Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides an amino acid infusion of breviscapine, which is characterized in that each bottle of amino acid infusion of breviscapine contains 0.02 to 0.20 g of breviscapine, amino acids providing nutrition, an energy agent and pharmaceutical excipient. The present invention has the advantages of stable quality, no stimulation and good curative effect, and also has the double efficiencies of promoting blood circulation to remove blood stasis and nutritional support simultaneously. The present invention can obtain valuable time for saving patients of emergency severe cases, simplify the operation of medical care personnel and reduce the labor intensity, and the present invention has very important significance for rescuing cardio-cerebrovascular patients with emergency severe cases and special patients in time.
Description
Technical field
The present invention relates to a kind of breviscapine amino acid transfusion and production method thereof of biologically active.
Background technology
Herba Erigerontis, existing formal name is called Herba Erigerontis, is the dry herb of Compositae Herba Erigerontis aceris platymiscium Herba Erigerontis [Erigeronbreviseapus (Vant.) Hand.-Mazz].Yunnan habit among the people claims Herba Erigerontis, Herba Erigerontis, TUXIXIN.Record in national standard.Said breviscapine is exactly the flavone compound that separation and Extraction is come out from Herba Erigerontis, and main component is a lamp-dish flower acetic, still contains a small amount of oil lamp cycle of sixty years element.Kinds such as breviscapine and injection thereof, tablet, injectable powder all have been national standard.Operative norm is WS3-B-3822-98, WS3-B-3879-98 etc., is a kind of plant amedica that Yunnan Province excavates out when going all out with Chinese herbal medicine in the period of 1970～1972.Through the Application and Development of three more than ten years, this product is by social sanction.At present existing or developing tablet, capsule, aqueous injection, injectable powder, sustained-release preparation etc. are arranged.But, still above-mentioned injection or injectable powder are added in the transfusion in a large number during use because aspects such as technology still do not have the large capacity transfusion agent of consumption maximum clinically so far.The problem that this usage exists is: strengthens nurse's workload, increases the chance of polluting, and time-consuming, be unfavorable for severe crisis patient's rescue etc.The patent application of relevant breviscapine also is a focus of field of medicaments in recent years, existing ten multinomial patent applications, the patent more relevant with the application has: serial crigeron breviscapus preparations for infusion (CN1191730A), stable prescription and the technical process (CN1187356A) of Breviscapini injection.CN1191730A is disclosed to be the glucose of Herba Erigerontis or the infusion solutions of sodium chloride.Because technical elements, this patent fail to implement so far.CN 1187356A discloses in the Breviscapini injection preparation and has added chelating agent, antioxidant etc., is intended to increase the stability of product.Since the L-sodium glutamate began to use, people were maked rapid progress to amino acid whose utilization, and particularly over past ten years, the aminoacid product enjoys people's attention, and its application is more extensive.Aspect medical, aminoacid is to constitute proteinic ultimate unit, participates in internal metabolism and various physiological function activity, both can be used as the nutritional supplementation that nutrient is used for human body, can be used for preventing and treating multiple disease again.Amino acid transfusion is exactly the serious achievement in the contemporary field of medicaments, is extremely important for severe crisis patient and especial patient.But amino acid transfusion can only be as a kind of nutritional support or supplement, and the severe crisis patient of cardiovascular and cerebrovascular disease often is starved of the medicine that in time gives blood circulation promoting and blood stasis dispelling, needs to import the nutritional support agent simultaneously.
Summary of the invention
The purpose of this invention is to provide a kind of steady quality, good effect and have blood circulation promoting and blood stasis dispelling and the breviscapine aminoacid large capacity transfusion agent of nutritional support double effects,, simplify the operation so that save the quality time that gives emergency treatment to a patient.
According to Clinical pathological study, in early stage 1～48 hour of morbidity, must suit the medicine to the illness stage by stage and individualized treatment, then need after 48 hours to replenish enough nutrition and support composition, in order to patients ' recovery to patient.Early stage some aminoacid of morbidity (as arginine etc.), vitamin C etc. all in clinical practice use in conjunction and obtain effect preferably in different phase.For patients with cerebral apoplexy,, therefore need with dehydrant (as mannitol, glycerol etc.) dehydration because cerebral edema is serious.If cardiac-cerebral ischemia and again the filling all can cause serious damage to heart and brain.Breviscapine can directly be removed free radical, and opposing ischemic injuries and reperfusion injury improve blood circulation and hemodynamics, and antithrombotic etc. can directly or indirectly be used for the treatment of disease.According to the normal demand of human body, aminoacids complex can be kept normal acid-base balance in the health, and best energy is provided, and corrects negative nitrogen balance in the body, keeps the human body positive nitrogen balance.From composition of prescription; the less stable of breviscapine in regular solution; but under occurrence of amino acid with multiple effects such as complexation, antioxidation, shieldings; breviscapine stable fine; with be equal in the former plant; the process conditions of (as nitrogen protection operation down) and relative gentle (rotation steriliser sterilization etc.) are controlled in the strictness of production technology in addition, have ensured the stability of product.So the present invention can provide a specific aim stronger, be applicable to ischemic cardiovascular and cerebral vascular disease patient's technical scheme.
Technical scheme provided by the invention is: every bottle of breviscapine amino acid transfusion contains breviscapine 0.02～0.20g, and aminoacid, caloric agent and pharmaceutic adjuvant that nutrition can be provided.
Described aminoacid is one or more in L-isoleucine in the essential amino acids, L-leucine, L-lysine acetate, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, the L-valine; and/or be in L-arginine in the semi-dispensable amino acid, L-tyrosine, the L-histidine one or more; and/or be L-alanine in the non essential amino acid, L-proline, L-serine, glycine, L-cystine, L-glutamic acid, L-aspartic acid, and in the taurine one or more.
Described caloric agent is one or more in sorbitol, L MALIC ACID, succinic acid, maleic acid, fumarase, glucose, lecithin, cephalin, the soybean phospholipid etc., so that the part heat is provided, prevent aminoacid as energy resource consumption, help improving amino acid whose utilization rate simultaneously.
Described pharmaceutic adjuvant is not for influencing vitamin riboflavin 5 '-phosphoric acid ester sodium, nicotiamide, glycerol, vitamin C, the B of transfusion and stability thereof
1, among the P, inositol one or more, and/or be a kind of or youngster's kind among the ginsenoside, Radix Panacis Quinquefolii saponin, arasaponin, gypenoside that can improve curative effect of medication, and/or for do not influence transfusion and can improve that sodium sulphite, sodium sulfite, pyrosulfurous acid in the stable antioxidant are received, in the cysteine one or more.
Described breviscapine amino acid transfusion makes by following process steps:
1, elder generation is dissolved in water for injection with the aminoacid of trace, and notes it is dissolved fully;
2, in breviscapine, add an amount of water for injection again, add above-mentioned injection aminoacid and other adjuvants again, and note it is dissolved fully;
3, add antioxidant, regulate to wait and ooze, add water for injection to finally volume required;
4, through coarse filtration, behind the fine straining, fine straining liquid is carried out packing, by every bottle of required ml packing, cover lid, the preparation preheating in 121 ℃ of sterilizations (15 minutes), or with the sterilization of rotation steriliser, is cooled off towards hot water gradually, gets product, and shady and cool place preserves.
Operation notice:
1, in whole process, notes leading to nitrogen or under nitrogen protection, operating, in case amino-acid oxidase;
2, antioxidant adds in the later stage as far as possible;
Temperature will keep even when 3, sterilizing.
Concrete operations are: under the condition of 10,000 grades and nitrogen protection; the aminoacid of trace is dissolved in water for injection in will writing out a prescription earlier; and note it is dissolved fully, in breviscapine, add an amount of water for injection, cause alkalescence (7.0～8.0) with rare adjusting PH with base; breviscapine is dissolved; adding water for injection is diluted to volume required, adds injection aminoacid and other adjuvants again, and notes it is dissolved fully; add antioxidant; regulate to wait and ooze, add water for injection, filter to finally volume required; after the filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m; under 100 grades condition, with the following filter membrane fine straining of 0.2 μ m, fine straining liquid is by every bottle of required ml packing; cover lid; preparation is carried out preheating, 121 ℃ of sterilizations 15 minutes, or with rotating the steriliser sterilization; after cooling off gradually towards hot water, shady and cool place preserves.
Breviscapine infusion agent with this law preparation our experiments show that:
1, stability: the breviscapine amino acid transfusion was placed 1 year at normal temperatures, and product is reliable and stable, and every index is all qualified, meets the requirement of injection fully;
2, zest: do irritant experiment with White Rabbit, the zest of breviscapine amino acid transfusion is 0 grade, does not promptly have significant change;
3, blood circulation promoting and blood stasis dispelling: breviscapine amino acid transfusion and the Breviscapini injection effect basically identical aspect blood circulation promoting and blood stasis dispelling.
Embodiment 1
The transfusion of preparation breviscapine eight seed amino acids, prescription (1000ml):
Breviscapine 0.08g L-isoleucine 3.82g
L-leucine 5.03g L-lysine acetate 4.52g
L-methionine 2.34g L-phenylalanine 5.65g
L-threonine 2.78g L-tryptophan 1.0g
L-valine 3.98g mannitol 70g
Preparation technology: under the condition of 10,000 grades and nitrogen protection, the L-tryptophan with trace is dissolved in 20ml water for injection earlier, and notes it is dissolved fully, and is stand-by; In breviscapine, add 20ml water for injection, regulate pH to 7.0～8.0, breviscapine is dissolved fully, filter with saturated solution of sodium bicarbonate, stand-by; Again other aminoacid are dissolved in 500ml water for injection, add above-mentioned solvent tryptophan liquid and breviscapine liquid, add mannitol and be diluted to 800ml with water for injection, add antioxidant, regulate to wait and ooze, add water for injection, filter to final volume required 1000ml; After the filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following filter membrane fine straining of 0.2 μ m; Fine straining liquid is sent into racking machine, by every bottle of required 250ml packing, cover the butyl rubber lid, preparation is carried out preheating, 121 ℃ of sterilizations 15 minutes, after cooling off gradually towards hot water, shady and cool place preserves, the breviscapine eight seed amino acids transfusion finished product of the specification of packing, check, qualified 4 bottles of 250ml: 20mg.
Embodiment 2
Preparation breviscapine and 11 kinds of amino acid transfusions, prescription (1000ml):
Breviscapine 0.20g L-isoleucine 3.72g
L-leucine 5.00g L-lysine acetate 4.32g
L-methionine 2.30g L-phenylalanine 5.60g
L-threonine 2.71g L-tryptophan 0.90g
L-valine 3.98g L-arginine hydrochloride 5.10g
L-tyrosine 0.27g L-histidine 2.10g
Sorbitol 60g
Preparation technology makes 11 kinds of amino acid transfusion finished products of breviscapine of the specification of 2 bottles of 500ml: 100mg with embodiment 1.
Embodiment 3
Preparation breviscapine and the transfusion of 18 seed amino acids, prescription (1000ml):
Breviscapine 0.40g L-isoleucine 3.52g
L-leucine 4.80g L-lysine acetate 4.12g
L-methionine 2.10g L-phenylalanine 5.22g
L-threonine 2.40g L-tryptophan 0.80g
L-valine 3.63g L-arginine hydrochloride 4.90g
L-tyrosine 0.24g L-histidine 2.00g
L-alanine 1.95g L-proline 1.00g
L-serine 1.00g glycine 7.56g
L-cystine 0.10g L-glutamic acid 0.75g
L-aspartic acid 2.50g sorbitol 50.00g
Preparation technology makes the breviscapine 18 seed amino acids transfusion finished product of the specification of 2 bottles of 500ml: 200mg with embodiment 1.
Embodiment 4
Preparation breviscapine and 18 seed amino acids and Radix Notoginseng total arasaponins transfusion, prescription (1000ml):
Breviscapine 0.20g L-isoleucine 3.52g
L-leucine 4.80g L-lysine acetate 4.12g
L-methionine 2.10g L-phenylalanine 5.22g
L-threonine 2.40g L-tryptophan 0.80g
L-valine 3.63g L-arginine hydrochloride 4.90g
L-tyrosine 0.24g L-histidine 2.00g
L-alanine 1.95g L-proline 1.00g
L-serine 1.00g glycine 7.56g
L-cystine 0.10g L-glutamic acid 0.75g
L-aspartic acid 2.50g L MALIC ACID 4g
Arasaponin 0.80g glucose 60g
Preparation technology makes the breviscapine 18 seed amino acid arasaponins transfusion finished product of the specification of 2 bottles of 500ml: 100mg with embodiment 1.
Embodiment 5
Preparation breviscapine and aminoacid and vitamin transfusion, prescription (1000ml):
Breviscapine 1.00g L-Potassium Magnesium Aspartata 20g
Mannitol 70g riboflavin 5 '-phosphoric acid ester sodium 0.4g
Preparation technology makes a kind of amino acid, vitamine transfusion of breviscapine finished product of the specification of 10 bottles of 100ml: 100mg with embodiment 1.
Embodiment 6
Preparation breviscapine and the transfusion of two seed amino acids, prescription (1000ml):
Breviscapine 0.20g L-lysine hydrochloride 4.32g
Lecithin 1.00g L-cysteine hydrochloride 1.07g
Sorbitol 66g fumarase 3.25g
Preparation technology makes the breviscapine two seed amino acids transfusion finished product of the specification of 10 bottles of 100ml: 20mg with embodiment 1.
Breviscapine amino acid transfusion provided by the invention is through study of pharmacy and part pharmacological research, and its result is reported as follows:
1, the stability of breviscapine amino acid transfusion
The lucifuge keeping at room temperature of six samples of embodiment was placed 1,2,3,6,12 month, checked that on time every bottle of outward appearance is constant substantially, and effective ingredient does not change through check yet.Therefore, think that tentatively product that the various prescriptions of this breviscapine infusion make all can reach the shelf-life about 1 year.
Assay and discriminating etc. the results are shown in Table 1 time with reference to existing GB in the quality standard.
2, the irritation test of breviscapine amino acid transfusion
Get 4 of healthy rabbits, W:2.0～2.2kg, male and female half and half, be divided into two groups, inject breviscapine infusion 1ml respectively on its left and right sides lower limb quadriceps femoris, 48h puts to death rabbit behind the medicine, cut open the inspection quadriceps femoris, vertically cut and observe injection site muscular irritation reaction, and converse corresponding order of reaction by table 2.
Table 1, breviscapine amino acid transfusion stability test result:
| Sample | Sample size, discriminating | ||||
| January | February | March | June | December | |
| Example 1 example 2 examples 3 examples 4 examples 5 examples 6 | Qualified qualified | Qualified qualified | Qualified qualified | Qualified qualified | Qualified qualified |
The result shows the sample of this invention preparation, and through the preliminarily stabilised investigation, product quality is basicly stable, can reach more than 1 year.
Table 2, local muscular irritation order of reaction table
| Order of reaction | Irritant reaction |
| 0 1 2 3 4 5 | No significant change mild hyperaemia, its scope is less than the hyperemia of 0.51.0cm moderate, its scope is less than the hyperemia of 0.51.0cm severe, necrosis occurs with myodegeneration, have the brown degeneration popularity necrosis to occur |
The result: the zest of breviscapine infusion is 0 grade;
3, the improving brain function effect of breviscapine amino acid transfusion
Cause the aged animal model for ICR mice retrobulbar injection D-galactose, the breviscapine amino acid transfusion (2.5,5,10ml/kg) that stomach gives various dose is irritated in grouping, once a day, continuous two weeks, test its influence then to aged animal intelligence, the result shows that product can improve the mice diving tower and walk the school grade of maze test, strengthens the maintenance to its memory.In addition, product can also obviously improve the content of aging model animal blood slurry superoxide dismutase (SOD), reduces the content of lipid peroxidation product malonaldehyde (MDA), has anti-oxidation function preferably.
1, material
1.1, laboratory animal ICR mice, body weight 20 ± 2g, male and female half and half.
1.2, medicine and reagent
1.2.1, test sample breviscapine 18 seed amino acid arasaponins transfusion (preproduction)
1.2.2, the reference substance Herba Erigerontis tablet, face the time spent, the carboxylic first fiber sodium with 1% is mixed with 5% suspension.
1.2.3, other reagent D-galactose, reagent two factories in Shanghai produce, lot number: 990102.O-phthalaldehyde(OPA), produce in Chinese Shanghai 5-linked chemical plant, lot number: 20010517.5-hydroxy tryptamine sulphuric acid flesh liver, Switzerland's import, Shanghai chemical reagent purchasing and supply station packing.Noradrenaline bitartrate, Shanghai Hefeng Pharmaceutical Co., Ltd. produces, lot number: 010908.Dopamine hydrochloride, Mingxing Pharmaceutical Factory, Guangzhou production, lot number: 9901001.All the other chemical reagent are the AR level.
1.3, main test apparatus 1, JN-A type precision torsion balance, Shanghai Second Balance Factory produces.2,7520 type spectrophotometers, analytical tool factory in Shanghai produces.3, MPF-4 type fluorescent spectrophotometer, Japan produces.4, superoxide dismutase testing cassete and malonaldehyde are measured test kit, and Nanjing is built up bio-engineering research and produced.
2, experimental technique and result
Earlier mice is divided into blank group and aging model group.Aging model group mice retrobulbar injection every day D-galactose 0.12mg/g, January continuously
[1]Divide some groups after the mice moulding as required again.Mice does following grouping at random during experiment: (1) blank group (not moulding of animal), irritate stomach N.S.(2) moulding matched group (animal-shaped) is irritated stomach N.S.(3) positive drug control group, animal-shaped, filling stomach brain-invigorating capsule solution (0.5g/kg is clinical two times of adult's dosage).(4)-(6) group is irritated stomach 2.5,5,10ml/kg respectively for the basic, normal, high dosage group of test group, and each is organized the mouse stomach volume and is 10ml/kg, once a day, and continuous two weeks.After the last administration, make following index determining.
2.1, product influence that the learning and memory of aging model mice is kept
2.1.1, the imitative literature method of step down test
[2], earlier mice was put into diving tower reaction chamber endoadaptation environment 3 minutes, pass to the 36V alternating current to the copper grid at the bottom of the reaction chamber then, after animal is shocked by electricity, tend to skip to platform, to keep away noxious stimulation.Because platform is narrow, inconvenience stops, and forces it to skip to the copper grid once more or repeatedly, but rebound platform promptly again after being shocked by electricity so trained 5 minutes, writes down the number of times that every Mus is shocked by electricity, with this school grade as this Mus.Recast test after 24 hours.During test, earlier mice is placed on the platform, time (incubation period) and the 3 minutes endogenous cause of ill that the record mice jumps off platform is for the first time jumped off platform and the number of times (being errors number) that shocked by electricity, with this index of keeping as memory.The results are shown in Table 1.
Table 1 product is to influence (diving tower method) x ± SD of aging model learning and memory of little mouse, n=20
| Group | Dosage (g/kg.d) | School grade | Memory is kept | ||
| The 5min errors number | Diving tower incubation period (second) | The 5min errors number | |||
| The contrast of blank assembly molding contrast positive drug | N.S 10ml N.S 10ml 0.5 | 3.2±1.2 ** 4.8±1.3 3.7±1.2 ** | 82.6±14.6 ** 50.4±12.2 63.2±15.5 **△△ | 3.9±1.5 ** 8.9±2.6 5.5±1.7 **△△ | |
| Product | Dosage high dose in the low dosage | 2.5 5.0 10.0 | 3.6±1.4 ** 3.8±1.3 ** 3.5±1.0 ** | 70.1±15.6 ** 78.7±17.6 ** 85.0±19.0 ** | 5.3±1.7 **△△ 4.3±1.6 ** 5.2±2.1 **△ |
Annotate: compare with the moulding matched group:
*: P＜0.05
*: P＜0.01.
Compare with the blank group:
△: P＜0.05;
△ △: P＜0.01
Above result shows, product significant prolongation mice diving tower incubation period, obviously reduces the errors number (P＜0.01) of diving tower simultaneously.
2.1.2, that square type maze test is got the qualified mice of moulding is a collection of, divide into groups and administration (or N.S) by above-mentioned test.Be administered to the 11st day, fasting was got the food training as the labyrinth after 12 hours.Mice is put into the starting area, arrives the target area through the rectangle labyrinth.Go to the wrong way in the way, help its correction.Reach its feed of target area relief 5 minutes.So practise 10 times every day, continuous three days.The 4th day (being the fortnight of administration) formal experiment.Each group is chosen 20 of the consistent mices of motility, and the record mice arrives the time of target area and the number of times of going to the wrong way midway from the starting area
[3]Doing the merging of twice, two secondary data continuously averages as the school grade of mice.Animal continues administration, repeats above-mentioned test after the week, and what the gained data were promptly represented to remember keeps, and the results are shown in Table 2:
Table 2 product is to improvement effect (maze method) x ± SD n=20 of aging model learning and memory of little mouse
| Group | Dosage (g/kg.d) | Learning period arrives the target area | The arrival target area is kept in memory | |||
| Required time (second) | Errors number | Required time (second) | Errors number | |||
| The contrast of blank assembly molding matched group positive drug | N.S 10ml N.S 10ml 0.5 | 31.2±6.5 ** 46.9±10.3 38.9±7.1 * | 3.5±1.3 ** 4.9±1.5 3.0±1.0 ** | 39.9±9.8 ** 52.5±9.8 39.1±5.2 ** | 3.9±1.5 ** 5.9±1.4 3.4±0.8 ** | |
| Product | Dosage high dose in the low dosage | 2.5 5.0 10.0 | 40.1±6.3 *△△ 37.7±7.2 **△△ 34.3±5.3 ** | 3.1±0.9 ** 3.1±0.8 ** 2.5±1.1 **△ | 43.4±6.8 ** 40.3±6.6 ** 37.7±4.6 ** | 3.7±1.2 ** 3.8±0.8 ** 2.9±0.8 **△ |
Annotate: compare with the moulding matched group:
*: P＜0.05
*: P＜0.01.
Compare with the blank group:
△: P＜0.05;
△ △: P＜0.01
Above result shows that product obviously improves the school grade that the aging model mice walks the labyrinth, reduces the memory phase of keeping and walks the errors number that the labyrinth takes place, and promptly strengthens the maintenance effect of mice to memory.
2.2 product is to the influence of aging model mice serum MDA and SOD content
It is a collection of to get mice, and grouping and dosage and method are tested with above-mentioned 1.2.1.But administration (or N.S) time is two courses of treatment (28 days), gets blood and gets the full brain of mice from femoral artery in one hour after the last administration.Measure the content of respectively organizing malonaldehyde in the mice serum (MDA) and superoxide dismutase (SOD) respectively by the described method of testing cassete that Nanjing is built up bio-engineering research and provided
[4]Measure the content of monoamine neurotransmitter in the mouse brain tissue with fluorescence spectrophotometry.Operational approach and result are as follows:
The assay of serum malonaldehyde (MDA), the according to the form below operation
| Standard pipe | The blank pipe of standard | Measure pipe | Measure blank pipe | |
| 10nmol/m standard substance (ml) | 0.1 | |||
| Dehydrated alcohol (ml) | 0.1 | |||
| Specimen (ml) | 0.1 | 0.1 | ||
| Reagent one (ml) | 0.1 | 0.1 | 0.1 | 0.1 |
Mixing (shaking several test tube racks down)
| Reagent two (ml) | 3 | 3 | 3 | 3 |
| Reagent three (ml) | 1 | 1 | 1 | |
| 50% glacial acetic acid (ml) | 1 |
Vortex vortex mixer mixing, the test tube mouth is tightened with antistaling film, sting an aperture,, take out back flowing water cooling in 95 ℃ of water-baths 40 minutes, centrifugal then (4000rpm) 10 minutes, get supernatant, the 1cm of 532nm place optical path, distilled water zeroing colorimetric, survey and respectively manage the absorbance value, press the content of MDA in the column count serum again:
The vitality test of serum superoxide dismutases (SOD), the according to the form below operation
| Reagent | Measure pipe | Control tube |
| No. 1 reagent (ml) | 1.00 | 1.0 |
| Sample (ml) | 0.03 | |
| Distilled water (ml) | 0.50 | 0.5+0.03 |
| No. 2 reagent (ml) | 0.1 | 0.1 |
| No. 3 reagent (ml) | 0.1 | 0.1 |
| No. 4 reagent (ml) | 0.1 | 0.1 |
With the abundant mixing of vortex vortex mixer, put 37 ℃ of waters bath with thermostatic control 40 minutes
| Developer (ml) | 2 | 2 |
Mixing is poured into after 10 minutes in the 1cm optical path cuvette, and the distilled water zeroing in wavelength 550nm place colorimetric, is calculated as follows SOD vigor (nu/ml)
The results are shown in Table 3:
Table 3 product is to the x ± SD that influences of mice plasma MDA and SOD
| Group | Dosage (g/kg.d) | n | MDA(nmol/ml) | SOD(nu/ml) | |
| Blank model contrast positive drug is right | N.S 10ml N.S 10ml 0.5 | 20 20 20 | 7.1±0.8 ** 10.6±1.1 7.9±0.8 ** | 87.9±21.0 ** 37.5±15.0 50.8±11.5 **△△ | |
| Logical relieving capsule | Dosage high dose in the low dosage | 0.5 1.0 2.0 | 20 20 20 | 7.7±0.9 ** 7.4±0.9 ** 7.2±1.0 ** | 55.1±10.3 **△△ 57.6±13.3 **△△ 68.0±12.6 **△△ |
Annotate: compare with the moulding matched group:
*: P＜0.05
*: P＜0.01.
Compare with the blank group:
△: P＜0.05;
△ △: P＜0.01
Above result shows that product can obviously reduce the activity of blood plasma lipide peroxidating content of mda and raising blood plasma superoxide dismutase (SOD).
Claims (6)
1, a kind of breviscapine amino acid transfusion is characterized in that containing in the 1000ml transfusion:
The different bright ammonia 3.82g of breviscapine 0.08g L-
L-leucine 5.03g L-lysine acetate 4.52g
L-methionine 2.34g L-phenylalanine 5.65g
L-threonine 2.78g L-tryptophan 1.0g
L-valine 3.98g mannitol 70g.
2, a kind of breviscapine amino acid transfusion is characterized in that containing in the 1000ml transfusion:
Breviscapine 0.20g L-isoleucine 3.72g
L-leucine 5.00g L-lysine acetate 4.32g
L-methionine 2.30g L-phenylalanine 5.60g
L-threonine 2.71g L-tryptophan 0.90g
L-valine 3.98g L-arginine hydrochloride 5.10g
L-tyrosine 0.27g L-histidine 2.10g
Sorbitol 60g.
3, a kind of breviscapine amino acid transfusion is characterized in that containing in the 1000ml transfusion:
Breviscapine 0.40g L-isoleucine 3.52g
L-leucine 4.80g L-lysine acetate 4.12g
L-methionine 2.10g L-phenylalanine 5.22g
L-threonine 2.40g L-tryptophan 0.80g
L-valine 3.63g L-arginine hydrochloride 4.90g
L-tyrosine 0.24g L-histidine 2.00g
L-alanine 1.95g L-proline 1.00g
L-serine 1.00g glycine 7.56g
L-cystine 0.10g L-glutamic acid 0.75g
L-aspartic acid 2.50g sorbitol 50.00g.
4, a kind of breviscapine amino acid transfusion is characterized in that containing in the 1000ml transfusion:
Breviscapine 0.20g L-isoleucine 3.52g
L-leucine 4.80g L-lysine acetate 4.12g
L-methionine 2.10g L-phenylalanine 5.22g
L-threonine 2.40g L-tryptophan 0.80g
L-valine 3.63g L-arginine hydrochloride 4.90g
L-tyrosine 0.24g L-histidine 2.00g
L-alanine 1.95g L-proline 1.00g
L-serine 1.00g glycine 7.56g
L-cystine 0.10g L-glutamic acid 0.75g
L-aspartic acid 2.50g L MALIC ACID 4g
Arasaponin 0.80g glucose 60g.
5, a kind of breviscapine amino acid transfusion is characterized in that containing in the 1000ml transfusion:
Breviscapine 1.00g L-Potassium Magnesium Aspartata 20g
Mannitol 70g riboflavin 5-phosphoric acid ester sodium 0.4g.
6, a kind of breviscapine amino acid transfusion is characterized in that containing in the 1000ml transfusion:
Breviscapine 0.20g L-lysine hydrochloride 4.32g
Lecithin 1.00g L-cysteine hydrochloride 1.07g
Sorbitol 66g fumarase 3.25g.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1187356A (en) * | 1997-01-08 | 1998-07-15 | 大连弘丰制药厂 | Stable prescription and process of fleabane extract injection |
| CN1425385A (en) * | 2002-12-19 | 2003-06-25 | 上海博泰医药科技有限公司 | Breviscapine infusion preparation and its preparing method |
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2003
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1187356A (en) * | 1997-01-08 | 1998-07-15 | 大连弘丰制药厂 | Stable prescription and process of fleabane extract injection |
| CN1425385A (en) * | 2002-12-19 | 2003-06-25 | 上海博泰医药科技有限公司 | Breviscapine infusion preparation and its preparing method |
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