CN105106110A - Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition - Google Patents
Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition Download PDFInfo
- Publication number
- CN105106110A CN105106110A CN201510610529.XA CN201510610529A CN105106110A CN 105106110 A CN105106110 A CN 105106110A CN 201510610529 A CN201510610529 A CN 201510610529A CN 105106110 A CN105106110 A CN 105106110A
- Authority
- CN
- China
- Prior art keywords
- puerarin
- medicine
- injection preparation
- injection
- preparation
- 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.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses an injectable medicine composition capable of improving the stability of a puerarin medicine injection preparation and a preparation method of the injectable medicine composition. The injectable medicine composition is mainly prepared by dissolving a puerarin salt in water for injection to obtain a liquid medicine, and adding citric acid and/or sodium citrate as a pH regulator to regulate the pH value of the liquid medicine, wherein the dose of citric acid and/or sodium citrate is 0.1-200.0 mg/100 ml. Through adoption of the injectable medicine composition, the pH value of the puerarin medicine injection preparation can be more stable; compared with those in the prior art, degraded substances in puerarin are greatly reduced; under the circumstance that other solubilizing agents increasing the clinical application risk are avoided, the clarity of the puerarin medicine injection preparation is improved; particularly, the problem that when the conventional puerarin injection product is stored for a relatively long time, small white dots and white blocks are generated to result in solution turbidity can be solved. Therefore, examination of visible foreign matters in the puerarin medicine injection preparation can be guaranteed to accord with the medicine quality standard regulation, and clinical medication and promotion are facilitated.
Description
Technical field
The invention belongs to medical art, specifically refer to a kind of medicinal composition for injections improving puerarin drug injection preparation stability.
Background technology
Puerarin is the alkaloid extracted from Chinese medicine Herba Gelsemii Elegantis, chemical constitution is tetramethylpyazine, it is a kind of novel agents of calcium ion antagonist, there is blood circulation promoting and blood stasis dispelling, anti-platelet aggregation, excited medullary respiratory center and vasomotor center, blood vessel dilating and bronchial smooth muscle, improve the multiple effects such as microcirculation, clinical for for obliterated cerebral vascular disease if incomplete brain blood supply, cerebral thrombosis, cerebral embolism and other ischemic angiopathys are as coronary heart disease, vasculitis etc.The injection of puerarin is for the modern difficult disease of Chinese medicine makes very big contribution.
Due to puerarin dissolubility extreme difference in aqueous, be therefore made into puerarin hydrochlorate or puerarin phosphate to increase its water solublity.Puerarin injection commercially available at present mainly contains puerarin hydrochlorate, the phosphatic injection with small volume of puerarin, and in puerarin hydrochlorate, puerarin phosphate solution, add the high-capacity injection that glucose or sodium chloride makes as osmotic pressure regulator.But when preparing above-mentioned injection, the pH value of medicinal liquid must be adjusted to the certain limit of applicable human injection's administration, the pH value regulator that current bibliographical information uses is sodium hydroxide solution or uses hydrochloric acid solution, phosphoric acid solution, but the puerarin injection adopting above-mentioned pH value regulator to prepare easily separates out the precipitate such as tiny white point, white block, solution muddiness under long storage periods and winter low temperature condition, causes the visible foreign matters check item of product defective.Prior art adds polyoxyethylene sorbitan monoleate in the solution as cosolvent, occurs the sedimentary problems such as small particles, white block, solution are muddy to solve product.But polyoxyethylene sorbitan monoleate is owing to having the effect of haemolysis and blood pressure lowering, and easily become sour in storage and autoclaving process, cause the injection clinical practice risk containing polyoxyethylene sorbitan monoleate higher, make troubles to clinical application and popularization.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of medicinal composition for injections improving puerarin drug injection preparation stability.This medicinal composition for injections adopts citric acid, sodium citrate as pH adjusting agent, and when finding to adopt citric acid, sodium citrate as pH adjusting agent by creative work, medicinal liquid pH value is more stable, puerarin degradation material comparatively prior art reduces greatly, when avoiding using other to increase the cosolvent of clinical practice risk, solve the problem that puerarin injection easily separates out tiny white point, white block, solution muddiness under long storage periods and winter low temperature condition satisfactorily.
The present invention's adopted technical scheme that solves the problem is: a kind of medicinal composition for injections improving puerarin drug injection preparation stability, salt primarily of puerarin is dissolved in water for injection, add osmotic pressure regulator, and adding the medicinal composition for injections that citric acid and/or sodium citrate regulate medicinal liquid pH value to make as pH adjusting agent, the consumption of described citric acid and/or sodium citrate is 0.1mg ~ 200.0mg/100ml.
Described osmotic pressure regulator is any one or a few in glucose, sodium chloride, xylitol, mannitol, fructose.The consumption of osmotic pressure regulator is prior art, and sodium chloride consumption is 0.9g/100ml; Glucose, xylitol, mannitol, fructose consumption are 5g/100ml ~ 10g/100ml.
The salt of described puerarin comprises puerarin hydrochlorate, puerarin phosphate.
The concentration of the salt of described puerarin is calculated as 10mg ~ 10g/100ml with puerarin.
Described medicinal liquid pH value is 3.0 ~ 6.0.
Described puerarin drug injection preparation formulation is injection.
The preparation method of the medicinal composition for injections of above-mentioned raising puerarin drug injection preparation stability, comprises the steps:
(1) salt of puerarin is taken with puerarin amount of calculation 0.1g ~ 100g, citric acid and/or sodium citrate 2mg ~ 4.0g;
(2) citric acid, sodium citrate are mixed with the solution of 10g/100ml ~ 20g/100ml respectively, for subsequent use;
(3) salt of puerarin, sodium chloride add in the water for injection 500ml of 30 DEG C ~ 40 DEG C, and be stirred to after dissolving completely, the active carbon added, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filtration decarburization;
(4) citric acid that configures of step (3) gained filtrate step (2) and/or liquor sodii citratis adjust ph are 3.0 ~ 7.0, add the water for injection of less than 40 DEG C (30 DEG C ~ 40 DEG C) to 1000ml;
(5) by the extremely clarification of step (4) gained medical filtration, fill, sterilizing, to obtain final product.
The middle citric acid consumption of described step (1) is 1mg ~ 2.0g, sodium citrate consumption is 1mg ~ 2.0g.
Described step also comprises osmotic pressure regulator 9.0g in (1).
Described osmotic pressure regulator is sodium chloride.
In such scheme, add citric acid and/or sodium citrate and refer to that what add can be any one in citric acid, sodium citrate, or citric acid, sodium citrate is with arbitrary proportion proportioning; In step (2), the one in the citric acid added, sodium citrate, then make a kind of solution, as comprised citric acid, sodium citrate two kinds, is then mixed with solution for standby respectively; The salt of puerarin, the consumption of osmotic pressure regulator can adopt the consumption of prior art, and the consumption according to prior art adjusts.
In sum, the invention has the beneficial effects as follows: the present invention studies discovery by experiment, in puerarin drug injection preparation, adopt citric acid, when sodium citrate is as pH adjusting agent, medicinal liquid pH value is more stable, puerarin degradation material comparatively prior art reduces greatly, when avoiding using other to increase the cosolvent of clinical practice risk, solving puerarin injection satisfactorily adopts prior art products easily to separate out tiny white point in storage process, white block, the problem of solution muddiness, can ensure that the visible foreign matters of the maintenance injection that puerarin injection can be stable in storage process detects the regulation meeting drug standard, be convenient to clinical application and popularization.
The present invention passes through creative work, the reason of the tiny white point of separating out in puerarin injection, white block, solution muddiness is analyzed and studied, determine deposit mainly raw material free alkali crystallize and a small amount of catabolite, occur that above-mentioned reason may be relevant with the kind of the pH value of solution and pH adjusting agent acid used, alkali.Therefore use sodium citrate as pH adjusting agent, and use citric acid as pH value counter regulation agent, when avoiding using other to increase the cosolvent of clinical practice risk, to solve the problem that this product easily separates out tiny white point, white block, solution muddiness under long storage periods and winter low temperature condition.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but embodiments of the present invention are not limited thereto.
embodiment 1
Improve a preparation method for the medicinal composition for injections of puerarin drug injection preparation stability, comprise the steps: that (1) weighting raw materials is with puerarin amount of calculation 0.1g ~ 100g, sodium chloride 9.0g, citric acid 1mg ~ 2.0g, sodium citrate 1mg ~ 2.0g; (2) citric acid, sodium citrate are mixed with the solution of 10% ~ 20% respectively, for subsequent use.(3) add in the water for injection 500ml of less than 40 DEG C, be stirred to completely dissolve after, add 0.02%(g/ml) active carbon, stirs 15 minutes, filtration decarburization.(4) filtrate citric acid or liquor sodii citratis adjust ph are 3.0 ~ 7.0, add the water for injection of less than 40 DEG C to 1000ml; (5) medical filtration is to clarification, and fill, sterilizing, to obtain final product.
Composition and the content thereof of the concrete each component of the present embodiment are as follows:
Hydrochloric acid puerarin 0.8g
Sodium chloride 9.0g
Citric acid 1.0g
Sodium citrate 2.0g
Citric acid, sodium citrate are mixed with the solution of 10% ~ 20% respectively, for subsequent use.Hydrochloric acid puerarin, sodium chloride add in the water for injection 500ml of less than 40 DEG C, are stirred to after dissolving completely, add the active carbon (namely activated carbon dosage is 0.02g/100ml) of 0.02%, stir 15 minutes, filter decarburization.Filtrate citric acid or liquor sodii citratis adjust ph are 3.8 ~ 4.2, add the water for injection of less than 40 DEG C to 1000ml.Medical filtration is to clarification, and fill, sterilizing, to obtain final product.
embodiment 2
Or the medicinal composition for injections of above-mentioned raising puerarin drug injection preparation stability is prepared in the steps below:
(1) weighting raw materials is with puerarin amount of calculation 0.1g ~ 100g, citric acid 1mg ~ 2.0g, sodium citrate 1mg ~ 2.0g; (2) citric acid, sodium citrate are mixed with the solution of 10% ~ 20% respectively, for subsequent use.(3) add in the water for injection 500ml of less than 40 DEG C, be stirred to completely dissolve after, add 0.02%(g/ml) active carbon, stirs 15 minutes, filtration decarburization.(4) filtrate citric acid or liquor sodii citratis adjust ph are 3.0 ~ 7.0, add the water for injection of less than 40 DEG C to 1000ml; (5) medical filtration is to clarification, and fill, sterilizing, to obtain final product.
Composition and the content thereof of the concrete each component of the present embodiment are as follows:
Hydrochloric acid puerarin 20g
Citric acid 1.0g
Sodium citrate 2.0g
Citric acid, sodium citrate are mixed with the solution of 10% ~ 20% respectively, for subsequent use.Hydrochloric acid puerarin adds in the water for injection 500ml of less than 40 DEG C, is stirred to after dissolving completely, adds the active carbon (namely activated carbon dosage is 0.02g/100ml) of 0.02%, stir 15 minutes, filters decarburization.Filtrate citric acid or liquor sodii citratis adjust ph are 3.8 ~ 4.2, add the water for injection of less than 40 DEG C to 1000ml.Medical filtration is to clarification, and fill, sterilizing, to obtain final product.
embodiment 3
The comparative test of puerarin eye drops stability
The visible foreign matters of puerarin eye drops obtained by the present invention is utilized to detect the regulation meeting drug standard, and stability of solution is fine, when avoiding using other to increase the cosolvent of clinical practice risk, solving puerarin eye drops in storage process, easily occurring the problems such as small particles, white block, solution are muddy.Utilize the puerarin eye drops obtained by the present invention according to the related request of China's coastal port two annex Ⅺ Ⅹ C pharmaceutical preparation stability test guidelines, investigate respectively and placed 20 days medicine stabilities at 25 DEG C of placements, 24 months, 40 DEG C placements, 6 months, 60 DEG C placements, 10 days, 0 ~ 5 DEG C low temperature, result is constant product quality at the conditions of the experiments described above, and every Testing index all meets the regulation of this product quality standard.
The pharmacological results shows: utilize stable puerarin eye drops obtained by the present invention without hemolytic, without anaphylaxis, nonirritant, meet the requirement of drug administration by injection.
According to the above results, puerarin drug injection preparation of the present invention can improve the clarity of puerarin injection, particularly when puerarin injection period of storage is longer, the visible foreign matters of maintenance injection that can be stable detects the regulation meeting drug standard, solving puerarin medicine adopts existing technical products to occur the problem of small particles, white block, solution muddiness when period of storage is longer, can ensure that the visible foreign matters inspection of product meets the regulation of drug standard, be convenient to clinical application and popularization.
As mentioned above, just the present invention can be realized preferably.
Claims (6)
1. one kind is improved the medicinal composition for injections of puerarin drug injection preparation stability, it is characterized in that, salt primarily of puerarin is dissolved in water for injection, add the medicinal composition for injections that citric acid and/or sodium citrate regulate medicinal liquid pH value to make as pH adjusting agent, the consumption of described citric acid and/or sodium citrate is 0.1mg ~ 200.0mg/100ml.
2. a kind of medicinal composition for injections improving puerarin drug injection preparation stability according to claim 1, it is characterized in that, also comprise osmotic pressure regulator, described osmotic pressure regulator is any one or a few in glucose, sodium chloride, xylitol, mannitol, fructose.
3. a kind of medicinal composition for injections improving puerarin drug injection preparation stability according to claim 1, is characterized in that, the salt of described puerarin comprises puerarin hydrochlorate, puerarin phosphate.
4. a kind of medicinal composition for injections improving puerarin drug injection preparation stability according to claim 1 or 3, it is characterized in that, the concentration of the salt of described puerarin is calculated as 10mg ~ 10g/100ml with puerarin.
5. a kind of medicinal composition for injections improving puerarin drug injection preparation stability according to claim 1, is characterized in that, described medicinal liquid pH value is 3.0 ~ 6.0.
6. a kind of medicinal composition for injections improving puerarin drug injection preparation stability according to claim 1, is characterized in that, described puerarin drug injection preparation formulation is injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510610529.XA CN105106110A (en) | 2015-09-23 | 2015-09-23 | Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510610529.XA CN105106110A (en) | 2015-09-23 | 2015-09-23 | Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105106110A true CN105106110A (en) | 2015-12-02 |
Family
ID=54654398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510610529.XA Pending CN105106110A (en) | 2015-09-23 | 2015-09-23 | Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105106110A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344506A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Preparation method of berberine injection preparation pharmaceutical composition |
| CN106344503A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Method for preparing pharmaceutical composition of lutein injection preparation |
| CN106344501A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation |
| CN106361803A (en) * | 2016-11-06 | 2017-02-01 | 成都先先先生物科技有限公司 | Pharmaceutical composition for injection for improving stability of Astragalus membranaceus medicine injection preparation |
| CN106377592A (en) * | 2016-11-06 | 2017-02-08 | 成都先先先生物科技有限公司 | Pharmaceutical composition for injection capable of improving stability of Yinzhihuang medication injection agent |
| CN106377571A (en) * | 2016-11-06 | 2017-02-08 | 成都先先先生物科技有限公司 | Method for preparing pharmaceutical composition of milkvetch root injection preparation |
| CN106420918A (en) * | 2016-11-06 | 2017-02-22 | 成都先先先生物科技有限公司 | Pharmaceutical composition used for injection and enhanced in stability of Danhong pharmaceutical injection preparation |
| CN106474056A (en) * | 2016-11-06 | 2017-03-08 | 成都先先先生物科技有限公司 | A kind of medicinal composition for injections improving phylloxanthin drug injection preparation stability |
| CN106474186A (en) * | 2016-11-06 | 2017-03-08 | 成都先先先生物科技有限公司 | A kind of preparation method improving DANHONG drug injection preparation stability |
| CN113143861A (en) * | 2021-06-15 | 2021-07-23 | 华北制药股份有限公司 | Puerarin composition for injection and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1389211A (en) * | 2002-07-18 | 2003-01-08 | 北京四环科宝制药有限公司 | Puerarin injection and its prepn. process |
| CN101416939A (en) * | 2008-12-02 | 2009-04-29 | 上海华源药业（宁夏）沙赛制药有限公司 | Puerarin liquid formulation and preparation method thereof |
| CN104688672A (en) * | 2014-12-29 | 2015-06-10 | 浙江莎普爱思药业股份有限公司 | Application of puerarin gel eye drop in preparation of drugs for treating ischemic ocular fundus diseases |
-
2015
- 2015-09-23 CN CN201510610529.XA patent/CN105106110A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1389211A (en) * | 2002-07-18 | 2003-01-08 | 北京四环科宝制药有限公司 | Puerarin injection and its prepn. process |
| CN101416939A (en) * | 2008-12-02 | 2009-04-29 | 上海华源药业（宁夏）沙赛制药有限公司 | Puerarin liquid formulation and preparation method thereof |
| CN104688672A (en) * | 2014-12-29 | 2015-06-10 | 浙江莎普爱思药业股份有限公司 | Application of puerarin gel eye drop in preparation of drugs for treating ischemic ocular fundus diseases |
Non-Patent Citations (1)
| Title |
|---|
| 徐俭等: "生产厂房、设备变化对葛根素注射液稳定性影响的研究", 《齐齐哈尔医学院学报》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344506A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Preparation method of berberine injection preparation pharmaceutical composition |
| CN106344503A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Method for preparing pharmaceutical composition of lutein injection preparation |
| CN106344501A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation |
| CN106361803A (en) * | 2016-11-06 | 2017-02-01 | 成都先先先生物科技有限公司 | Pharmaceutical composition for injection for improving stability of Astragalus membranaceus medicine injection preparation |
| CN106377592A (en) * | 2016-11-06 | 2017-02-08 | 成都先先先生物科技有限公司 | Pharmaceutical composition for injection capable of improving stability of Yinzhihuang medication injection agent |
| CN106377571A (en) * | 2016-11-06 | 2017-02-08 | 成都先先先生物科技有限公司 | Method for preparing pharmaceutical composition of milkvetch root injection preparation |
| CN106420918A (en) * | 2016-11-06 | 2017-02-22 | 成都先先先生物科技有限公司 | Pharmaceutical composition used for injection and enhanced in stability of Danhong pharmaceutical injection preparation |
| CN106474056A (en) * | 2016-11-06 | 2017-03-08 | 成都先先先生物科技有限公司 | A kind of medicinal composition for injections improving phylloxanthin drug injection preparation stability |
| CN106474186A (en) * | 2016-11-06 | 2017-03-08 | 成都先先先生物科技有限公司 | A kind of preparation method improving DANHONG drug injection preparation stability |
| CN113143861A (en) * | 2021-06-15 | 2021-07-23 | 华北制药股份有限公司 | Puerarin composition for injection and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102008727B (en) | Injection-purpose medicine composition for improving stability of ligustrazine medicine injection formulation | |
| CN105106110A (en) | Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition | |
| CN105125485A (en) | Preparation method of injecting drug improving stability of puerarin drug injection preparation | |
| CN105963247A (en) | Preparation method of injection medicine for improving stability of quercetin medicine injection preparation | |
| CN106361969A (en) | Preparation method of drug composition for improving stability of Shengmai drug injection preparation | |
| CN106474056A (en) | A kind of medicinal composition for injections improving phylloxanthin drug injection preparation stability | |
| CN106389315A (en) | Injection pharmaceutical composition for improving stability of sharpleaf galangal fruit drug injection preparation | |
| CN106361693A (en) | Preparation method of leech injection preparation pharmaceutical composition | |
| CN106344502A (en) | Pharmaceutical composition for injection capable of improving stability of leech drug injection preparation | |
| CN106344636A (en) | Preparation method of Chinese thorowax root injection preparation pharmaceutical composition | |
| CN105902487A (en) | Injection pharmaceutical composition capable of improving stability of quercetin medication injection preparation | |
| CN106389316A (en) | Injection pharmaceutical composition capable of improving stability of abrotani herba drug injection preparation | |
| CN106214629A (en) | A kind of preparation method of breviscapine drug injection preparation stability compositions | |
| CN106377592A (en) | Pharmaceutical composition for injection capable of improving stability of Yinzhihuang medication injection agent | |
| CN105999278A (en) | Injecting medicine composition for improving stability of ginsenoside medicine injection | |
| CN106344503A (en) | Method for preparing pharmaceutical composition of lutein injection preparation | |
| CN106344501A (en) | Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation | |
| CN106361692A (en) | Injection pharmaceutical composition capable of enhancing radix bupleuri pharmaceutical injection preparation stability | |
| CN106377571A (en) | Method for preparing pharmaceutical composition of milkvetch root injection preparation | |
| CN106361803A (en) | Pharmaceutical composition for injection for improving stability of Astragalus membranaceus medicine injection preparation | |
| CN106389321A (en) | Pharmaceutical composition capable of improving stability of Shenmai drug injection | |
| CN106361855A (en) | Method for preparing pharmaceutical composition of Yinzhihuang injection | |
| CN106511424A (en) | Preparation method of herba artemisiae annuae injection preparation medicinal composition | |
| CN106344506A (en) | Preparation method of berberine injection preparation pharmaceutical composition | |
| CN106176589A (en) | Improve the medicinal composition for injections of quinidine sulfate drug injection preparation stability |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20151202 |