CN1579386A - Armillarisin A solution preparation and its preparing method - Google Patents
Armillarisin A solution preparation and its preparing method Download PDFInfo
- Publication number
- CN1579386A CN1579386A CN 200410020563 CN200410020563A CN1579386A CN 1579386 A CN1579386 A CN 1579386A CN 200410020563 CN200410020563 CN 200410020563 CN 200410020563 A CN200410020563 A CN 200410020563A CN 1579386 A CN1579386 A CN 1579386A
- Authority
- CN
- China
- Prior art keywords
- armillarisin
- solution
- polyethylene glycol
- water
- preparation according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an armillarisin preparation and its manufacturing method, it has characters of quick stripping, scattering and absorption, the individual difference of effect is small and has advantage to disease treatment. It produces solution armillarisin with compound solution of polyethylene glycol and other solutions, and it can be produced into liquid soft capsule, liquid hard capsule and drop preparation. The molecular weight of polyethylene glycol is 200-4000 of polyethylene glycol. The other solutions are propylene glycol, glycerine, alcohol and water. Takes the polyethylene glycol, armillarisin with prescription content and heats then to 45-75deg.C, adds in glycerine, water and stabilizer after being dissolved, then cools them to room temperature, the pH value is regulated to 3-9, filters, acquires the liquid, then the acquired liquid can be sued to produce soft capsule and hard capsule.
Description
Technical field:
The present invention relates to medical technical field, exactly it is armillarisin A solution type preparation and preparation method thereof.
Background technology:
Armillarisin A solution can promptly be encircled in the Pseudomonas armillariella tabescens by Armillaria mella tabescens (Scop.ex Fr.) Sing. and extract, but also synthetic, and its character is yellow or light yellow needle-like or crystalline powder, and the effect that promotes bile secretion is arranged, and the 0ddis sphincter is had tangible spasmolysis.In addition, may still have to promote immunologic function and strengthen cytophagous phagocytosis, but also transaminase lowering activity still can be decomposed aspergillus flavus toxin.Be applicable to acute cholecystitis, acute episode of chronic cholecystitis, chronic gastritis and viral hepatitis etc.
Armillarisin A is to separate on the folk remedy basis, and the choleretic of final synthetic, abroad seldom to its research, and it is domestic also few to its research, people's such as Sun Fenzhi result of study shows, the terminal sphincteral tensity of the loose ductus choledochus of energy can make hepatic secretion bile amount obviously increase simultaneously after anesthetized dog intravenous injection this product.After anesthesia rat duodenal administration or intramuscular injection this product, all can promote hepatic secretion bile.Can also cause after anesthetized dog intravenous injection this product that duodenum is loose, blood pressure reduces, decreased heart rate, act on all slight and of short duration.The acute LD of mice by intraperitoneal injection and oral this product
50Be respectively 980mg/kg and＞5000mg/kg.With 25～125 times of human maximum dose level every day respectively intramuscular injection in rat and Canis familiaris L., once a day, continuous three months, the result did not see obvious toxic and side effects (Sun Fenzhi, Deng. the pharmacology and the toxicity research of new choleretic armillarisin A: Acta Pharmaceutica Sinica 1981,16 (6): 401-406).Because armillarisin A soluble,very slightly in ethanol or methanol, almost insoluble in water, made injection need add multiple organic solvent, comprise polyethylene glycol 6000, ethanol, also added Tween 80 (Guo Jianlan simultaneously, Deng. the research pharmacy circular of Stability of Armillarisin A Injection: 1981,16 (11): 8-11).Though, in this prescription, having adopted Polyethylene Glycol, the molecular weight of Polyethylene Glycol only is 6000, the dosage form of being developed is an injection, does not see and adopts Polyethylene Glycol in the oral agents.
Armillarisin A is almost insoluble in water, and existing oral formulations clinical efficacy is often not good, for dissolubility in the water that improves armillarisin A, has literary composition to make polyvinylpyrrolidone (PVP) coprecipitate.Adopt the made coprecipitate of optimal proportion (1: 5) of document, in its water dissolubility only be 249.97ug/ml (Guo Jianlan, etc. the dissolubility pharmacy of improving armillarisin A with coprecipitation method circulates a notice of 1986,21 (5): 261,263); Simultaneously, there is " wearing out " problem in coprecipitate, and long term storage stability is poor.Zhu Jiabi etc. have developed instant (Zhu Jiabi, the development of armillarisin A dissolving tablet and choleretic effect research Acta Pharmaceutica Sinica 1992 thereof, 27 (3): 231～235), made instant of author is by starch, dextrin, an amount of homemade new adjuvant is formed, the stripping quantity of made dissolving tablet in the dissolution medium of being made up of 13.5ml dilute hydrochloric acid and 30% ethanol water (cumulative volume is 650ml) improves greatly than former tablet, but the time of its external stripping 63.2% is 8.5 minutes, we once made cyclodextrin clathrate with armillarisin A, shorten the external dissolution time of armillarisin A greatly, and applied for patent (application number: 02144851.5).In existing literature, do not see and adopt the solvent of Polyethylene Glycol kind solvent as oral formulations, we find that through a large amount of tests Polyethylene Glycol kind solvent and combination solvent thereof can dissolve armillarisin A makes solution, and can utilize this solution to make multiple oral formulations.Because in solution, medicine is to exist in the molecular state mode, and the stripping of medicine, dispersion, absorption are faster, and the curative effect individual variation is littler.Oral formulations is suitable for long-term prescription most.
Summary of the invention:
The objective of the invention is to be achieved by the following scheme, it is characterized in that: select Polyethylene Glycol (PEG200, PEG300, PEG400, PEG600) as solvent, or be aided with other solvents, stabilizing agent, pH regulator agent, preparation armillarisin A solution, Polyethylene Glycol with other solvent burden ratio is: Polyethylene Glycol, propylene glycol, glycerol, ethanol, water etc. mix by a certain percentage.The weight ratio of Polyethylene Glycol and propylene glycol, glycerol, ethanol, water is 1: 0～1: 0～1: 0～1: 0～1, and its optimum range is 1: 0.05～0.5: 0.05～0.5: 0～0.2: 0.1～0.5; The weight ratio of Polyethylene Glycol kind solvent and medicine is 100: 0.2～100: 10, and its optimum range is 100: 0.5～100: 3, and the solution available water of gained is diluted arbitrarily, can be made into dosage forms such as solution-type soft capsule, solution-type hard capsule and drop.The Polyethylene Glycol kind solvent is that molecular weight is 200～4000 Polyethylene Glycol.Described other solvents are propylene glycol, glycerol, ethanol, water.Can add stabilizing agent, pH regulator agent in the prepared armillarisin A solution.Said stabilizing agent comprises one or more mixture in sodium sulfite, sodium sulfite, tocopherol, the tocopheryl acetate etc.; The pH regulator agent is one or more mixture in citric acid, tartaric acid, hydrochloric acid, phosphoric acid, sodium hydroxide, carbonic acid (hydrogen) sodium etc., and the pH scope is: 3～9.Said double solvents is: Polyethylene Glycol, propylene glycol, glycerol, ethanol, water etc.Can add an amount of sweeting agent, essence in the said drop.
Advantage of the present invention is: because in solution, medicine is to exist in the molecular state mode, and the stripping of medicine, dispersion, absorption are faster, and the curative effect individual variation is littler, is beneficial to treatment of diseases.Oral formulations is suitable for long-term prescription most.
The specific embodiment:
Below in conjunction with embodiment the present invention is further illustrated, but not only be confined to listed embodiment.
Embodiment 1: the preparation of armillarisin A solution
Prescription:
Armillarisin A 0.5g
Macrogol 200 (PEG200) 100g
Hydrochloric acid is an amount of
Essence is an amount of
Preparation technology:
Take by weighing the Macrogol 200 and the armillarisin A of recipe quantity, place beaker, heat 50～60 ℃, stirring and dissolving after, add hydrochloric acid, transfer pH to about 3, be cooled to room temperature, add essence, filter, solution.Gained solution can be prepared into drop etc.
Embodiment 2: the preparation of armillarisin A solution
Prescription:
Armillarisin A 2g
PEG400 (PEG400) 100g
Glycerol 10g
Citric acid is an amount of
Water 2g
Preparation technology:
After taking by weighing 65～75 ℃ of PEG400, the armillarisin A heating, stirring and dissolving of recipe quantity, add glycerol, water, it is even to be mixed, and is cooled to room temperature, and citric acid transfers pH to about 5, filter, solution.Gained solution can be prepared into soft capsule, hard capsule etc.
Embodiment 3: the preparation of armillarisin A solution
Prescription:
Armillarisin A 5g
PEG400 (PEG400) 100g
Glycerol 15g
Sodium hydroxide is an amount of
Protein sugar is an amount of
Essence is an amount of
Sodium sulfite is an amount of
Water 80g
Preparation technology:
Take by weighing PEG400, glycerol and the armillarisin A of recipe quantity, place beaker, heat 60 ℃, stirring and dissolving after, add entry, sodium sulfite, it is even to be mixed, and is cooled to room temperature, transfers pH to 9 with sodium hydroxide, filter, solution.Gained solution can prepare drop etc.
Embodiment 4: the preparation of armillarisin A solution
Prescription:
Armillarisin A 5g
Macrogol 600 (PEG600) 20g
Macrogol 200 (PEG200) 100g
Propylene glycol 15g
Ethanol 5g
Sodium sulfite 0.1g
Hydrochloric acid is an amount of
Water 5g
Preparation technology:
Take by weighing Macrogol 600, Macrogol 200, propylene glycol, ethanol and the armillarisin A of recipe quantity, place beaker, heat 50 ℃, stirring and dissolving after, add entry, it is even to be mixed, and is cooled to room temperature, transfers pH to about 6 with hydrochloric acid, solution.Gained solution can be prepared into soft capsule, hard capsule.
Embodiment 5: the preparation of armillarisin A solution
Prescription:
Armillarisin A 1g
PEG400 (PEG400) 90g
Polyethylene Glycol 800 (PEG800) 10g
Glycerol 5g
Phosphoric acid is an amount of
Sodium hydroxide is an amount of
Water 1g
Preparation technology:
Take by weighing PEG400, Polyethylene Glycol 800, glycerol and the armillarisin A of recipe quantity, place beaker, heat 70 ℃, stirring and dissolving after, add entry, it is even to be mixed, and is cooled to room temperature, transfer pH to about 7 with phosphoric acid and sodium hydroxide, solution, make soft capsule, hard capsule.
Embodiment 6: the preparation of armillarisin A solution
Prescription:
Armillarisin A 1g
Macrogol 200 (PEG200) 99g
Macrogol 4000 (PEG4000) 1g
Propylene glycol 2g
Ethanol 0.5g
Tocopherol 0.1g
Water 2g
Preparation technology:
Take by weighing Macrogol 200, Macrogol 4000, propylene glycol, ethanol, tocopherol and the armillarisin A of recipe quantity, place beaker, add 60～70 ℃, stirring and dissolving after, add entry, it is even to be mixed, and is cooled to room temperature, solution.Gained solution can be prepared into soft capsule, hard capsule.
Embodiment 7: the preparation of armillarisin A solution
Prescription:
Armillarisin A 5g
PEG400 (PEG400) 35g
Macrogol 600 (PEG600) 15g
Glycerol 50g
Sodium hydroxide is an amount of
Protein sugar is an amount of
Essence is an amount of
Antiseptic is an amount of
Sodium sulfite 0.1g
Water 50g
Preparation technology:
Take by weighing PEG400, Macrogol 600, glycerol, the dissolving of water mixing of recipe quantity, add armillarisin A, transfer pH to about 8 with sodium hydroxide, after the stirring and dissolving, add sodium sulfite, protein sugar, essence, it is even to be mixed, and is cooled to room temperature, solution.Gained solution can be prepared into drop.
Embodiment 8: the preparation of armillarisin A solution
Prescription:
Armillarisin A 1g
PEG400 (PEG400) 99g
Cetomacrogol 1000 (PEG1000) 1g
Propylene glycol 2g
Hydrochloric acid is an amount of
Water 2g
Preparation technology:
Take by weighing PEG400, Polyethylene Glycol 100, propylene glycol and the armillarisin A of recipe quantity, place beaker, heat 60 ℃, stirring and dissolving after, add entry, it is even to be mixed, and transfers pH to about 4～6 with hydrochloric acid, is cooled to room temperature, solution.Gained solution can be prepared into soft capsule, hard capsule.
Embodiment 9: the drug effect of armillarisin A solution
One, armillarisin A is in the intravital function of gallbladder promoting experimental result of rat
Animal: the Wister rat, male.
Equipment: rat fixing head, biliary drainage pipe, bulk pruning cutter, operating scissors, flat tweezer, ophthalmology tweezer, eye scissors, mosquito forceps, syringe.
Reagent: armillarisin A; Armillarisin A solution (embodiment 2, self-control).
The medicine preparation: armillarisin A is made water suspension with 1% sodium carboxymethyl cellulose; Armillarisin A solution available water is diluted arbitrarily.
Method:
18 of male rats are divided into 3 groups at random after weighing, fasting be can't help water 12 hours before the experiment.During experiment every group with after the pentobarbital sodium 40mg/kg anesthesia, face upward the position and be fixed on the fixing head, cut about 2cm along the abdomen median line, open the abdominal cavity, find stomachus pyloricus, the upset duodenum, in the descendant duodenum mesentery, find the bile duct of white flexible, wear two rhizoid lines under it, the ligation pars papillaris is made v-notch to the liver direction, insert plastic tube, promptly as seen have pistac bile to flow out, ligation fixed plastics pipe is collected bile with test tube.After waiting after the operation to stablize 30 minutes, collect 30 minutes bile earlier, respectively organize rat then and give medicine by the dosage of 30mg/kg by duodenum respectively, capacity normal saline such as negative control group injection.
Collected bile once every 10 minutes after the administration, totally 3 times, the record bile flow, changing percentage rate with bile before and after the administration is statistical indicator.
The result:
The results are shown in following table,
Armillarisin A and solution thereof to the excretory influence of rat bile (x ± s, n=6)
Bile flow changes percentage rate
Medicine n
After the preceding administration of administration (min)
(min) 10 20 30
Normal saline 6 0.21 ± 0.12-3.08 ± 0.26-3.01 ± 0.11-3.20 ± 0.15
Armillarisin A 6 0.23 ± 0.11 16.3 ± 3.80
*18.6 ± 5.12
*16.5 ± 6.22
*
Armillarisin A
Solution 6 0.24 ± 0.12 31.2 ± 2.68
*38.8 ± 3.21
*28.8 ± 1.86
*
Δ Δ Δ
*P＜0.05,
*P＜0.01 armillarisin A and solution and normal saline group are relatively;
ΔP＜0.05 solution group and armillarisin A group are relatively.(list of references 1. Qi Chens. the herbal pharmacology research methodology. Beijing: People's Health Publisher, 1993; 2. Li Yi Kui, Wang Qinmao (chief editor). the herbal pharmacology experimental methodology. Shanghai: Science and Technology of Shanghai publishing house, 1991)
By above data as can be known, armillarisin A made solution after, not only have " rapid-action ", " curative effect height " characteristics, and " individual variation is little ", be beneficial to treatment of diseases.
Claims (9)
1, armillarisin A solution type preparation, it is characterized in that: by adopting the Polyethylene Glycol kind solvent and prepare the solution-type armillarisin A with the double solvents of other solvents combinations, and the solution-type dosage forms of making thus such as solution-type soft capsule, solution-type hard capsule and drop.
2, armillarisin A solution type preparation according to claim 1 is characterized in that: the Polyethylene Glycol kind solvent is that molecular weight is 200～4000 Polyethylene Glycol.
3, armillarisin A solution type preparation according to claim 1 is characterized in that: described other solvents are propylene glycol, glycerol, ethanol, water.
4, armillarisin A solution type preparation according to claim 1 is characterized in that: the weight ratio of described Polyethylene Glycol kind solvent and medicine is 100: 0.2～100: 10.
5, armillarisin A solution type preparation according to claim 1 is characterized in that: can add stabilizing agent, pH regulator agent in the prepared armillarisin A solution.
6, armillarisin A solution type preparation according to claim 5 is characterized in that: said stabilizing agent comprises one or more mixture in sodium sulfite, sodium sulfite, tocopherol, the tocopheryl acetate; The pH regulator agent is one or more mixture in citric acid, tartaric acid, hydrochloric acid, phosphoric acid, sodium hydroxide, carbonic acid (hydrogen) sodium, and the pH scope is: 3～9.
7, armillarisin A solution type preparation according to claim 1, it is characterized in that: said double solvents is: Polyethylene Glycol, propylene glycol, glycerol, ethanol, water, the weight ratio of Polyethylene Glycol and propylene glycol, glycerol, ethanol, water are 1: 0～1: 0～1: 0～1: 0～1.
8, armillarisin A solution type preparation according to claim 1 is characterized in that: can add an amount of sweeting agent, essence in the said drop.
9, a kind of armillarisin A solution type preparation as claimed in claim 1, it is characterized in that: after taking by weighing 45～75 ℃ of Polyethylene Glycol, the armillarisin A heating, stirring and dissolving of recipe quantity, adding glycerol, water, stabilizing agent are mixed even, be cooled to room temperature, transfer pH to 3～9, filter, get solution, gained solution can be prepared into soft capsule, hard capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200410020563A CN100588397C (en) | 2004-05-19 | 2004-05-19 | Armillarisin A solution preparation and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200410020563A CN100588397C (en) | 2004-05-19 | 2004-05-19 | Armillarisin A solution preparation and its preparing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1579386A true CN1579386A (en) | 2005-02-16 |
| CN100588397C CN100588397C (en) | 2010-02-10 |
Family
ID=34581877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200410020563A Expired - Fee Related CN100588397C (en) | 2004-05-19 | 2004-05-19 | Armillarisin A solution preparation and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100588397C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100420683C (en) * | 2006-09-21 | 2008-09-24 | 王绍杰 | Armillaria mellea A succinic acid monoester with cholagogic effect, salt thereof and medicinal composition |
| CN1895292B (en) * | 2006-06-28 | 2011-09-07 | 四川隆盛药业有限责任公司 | Leukothrix capsule medicine, its discrimination and quality standard inspection |
| CN104414971A (en) * | 2013-09-10 | 2015-03-18 | 成都力思特制药股份有限公司 | Armillarisin A injection and preparation method thereof |
-
2004
- 2004-05-19 CN CN200410020563A patent/CN100588397C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1895292B (en) * | 2006-06-28 | 2011-09-07 | 四川隆盛药业有限责任公司 | Leukothrix capsule medicine, its discrimination and quality standard inspection |
| CN100420683C (en) * | 2006-09-21 | 2008-09-24 | 王绍杰 | Armillaria mellea A succinic acid monoester with cholagogic effect, salt thereof and medicinal composition |
| CN104414971A (en) * | 2013-09-10 | 2015-03-18 | 成都力思特制药股份有限公司 | Armillarisin A injection and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100588397C (en) | 2010-02-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1652807A (en) | Formulations useful in the treatment of male and female impotence | |
| CN1579386A (en) | Armillarisin A solution preparation and its preparing method | |
| CN1709236A (en) | Fat emulsion containing docetaxel and its preparing method | |
| CN1879766A (en) | Medicine for treating rheumatism and preparation method thereof | |
| CN1507858A (en) | Flrorinated chloromycetin containing liquid preparation for animal | |
| CN101933900A (en) | Compound preparation for preventing and treating poultry liver diseases and preparation method thereof | |
| CN1179726C (en) | Application of naringin in preparing medicine for supporting treatment of SARS | |
| CN1748758A (en) | Dragon's blood gel preparation and its preparing method | |
| CN1720948A (en) | Dripping pills of lllicium henryi dripping pills and method for preparing the same | |
| CN1533770A (en) | Saspension injection containing benzimidazole kind vermifuge | |
| CN1939377A (en) | Chinese medicinal composition, its preparation and use in pharmacy | |
| CN1593449A (en) | self emulsifying soft capsule of breviscapine and its preparation | |
| CN1316958C (en) | Caulis Erycibes drop-pill and its preparation method | |
| CN1234403C (en) | Chinese medicine for treating gastric disease | |
| CN1634481A (en) | Honeysuckle flower soft capsule and preparation method thereof | |
| CN101036681A (en) | Analgesic aconitum flavum | |
| CN1682821A (en) | Compound radical lobelia dripping pill and its preparing method | |
| CN1307975C (en) | Safflower drop pills and preparation method thereof | |
| CN1493296A (en) | Hemsleya amabilis drip pill and its preparation method | |
| CN1682817A (en) | Throat dripping pill for clearing away heat and toxic material and its preparing method | |
| CN1939398A (en) | Use of gentiin in analgesic for treating arthritis | |
| CN1720946A (en) | Bone strengthening dripping pills with Premena fulva craib as raw material and method for preparing the same | |
| CN1709461A (en) | Calculus bovis detoxifying dropping pill, and its preparing method | |
| CN1679669A (en) | Polygala dropping balls and preparation thereof | |
| CN1628687A (en) | Medicine composition for treating prostatitis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100210 Termination date: 20120519 |