CN106214629A - A kind of preparation method of breviscapine drug injection preparation stability compositions - Google Patents
A kind of preparation method of breviscapine drug injection preparation stability compositions Download PDFInfo
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- CN106214629A CN106214629A CN201610646230.4A CN201610646230A CN106214629A CN 106214629 A CN106214629 A CN 106214629A CN 201610646230 A CN201610646230 A CN 201610646230A CN 106214629 A CN106214629 A CN 106214629A
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- breviscapine
- injection
- malic acid
- preparation
- natrium malicum
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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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- 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
- A61K9/08—Solutions
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Abstract
The invention discloses the preparation method of a kind of breviscapine drug injection preparation stability compositions, comprise the steps: 1) weigh breviscapine, malic acid and/or natrium malicum；2) malic acid, natrium malicum solution are joined respectively；3), during breviscapine adds the water for injection 500ml of 30 DEG C～40 DEG C, stir to after being completely dissolved, the activated carbon of addition, stirring, filter decarburization；4) malic acid and/or the natrium malicum solution regulation pH value of gained filtrate configuration is 4.0～6.0, addition water for injection to 1000ml；5) it is filtered until clear, fill, sterilizing, to obtain final product.The present invention can make this injection pH value more stable, breviscapine degradation material relatively prior art is substantially reduced, in the case of avoiding using other to increase the cosolvent of clinical practice risk, improve the clarity of Breviscapini injection, can ensure that the visible foreign matters inspection of product meets the regulation of drug standard, it is simple to clinical application and popularization.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to a kind of breviscapine drug injection preparation stability combination
The preparation method of thing.
Background technology
Breviscapine has the effect of expansion of cerebral vascular, can reduce cerebral vascular resistance, increases cerebral blood flow, improves micro-following
Ring, and have antiplatelet aggregative activity.Therefore can be used for treating ischemic cerebrovascular, such as cerebral thrombosis, cerebral embolism, brain
The caused sequela paralytic such as hemorrhage, has good therapeutic effect.
Due to breviscapine dissolubility extreme difference in aqueous, therefore it is made into breviscapine hydrochlorate or breviscapine
Phosphate is to increase its water solublity.Presently commercially available Breviscapini injection mainly has breviscapine hydrochlorate, breviscapine phosphorus
The injection with small volume of hydrochlorate, and in breviscapine extracting solution solution, add glucose or sodium chloride as osmotic pressure regulation
The high-capacity injection that agent is made.But when preparing above-mentioned injection, it is necessary to be adjusted to the pH value of medicinal liquid be suitable for human injection
The certain limit being administered, the pH value regulator that current document report uses is sodium hydroxide solution or uses hydrochloric acid solution, phosphorus
Acid solution, but the Breviscapini injection using above-mentioned pH value regulator to prepare is easy under the conditions of long-term storage and winter low temperature
Separating out the precipitate such as tiny white point, white block, solution muddiness, the visible foreign matters check item causing product is defective.Prior art is
Add polyoxyethylene sorbitan monoleate in the solution as cosolvent, occur that small particles, white block, solution are muddy etc. sedimentary solving product
Problem.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, lead
Cause the injection clinical practice risk containing polyoxyethylene sorbitan monoleate higher, make troubles to clinical application and popularization.
Summary of the invention
The technical problem to be solved is to provide a kind of breviscapine drug injection preparation stability compositions
Preparation method.This medicinal composition for injections employing malic acid, natrium malicum are as pH adjusting agent, and are sent out by creative work
When now using malic acid, natrium malicum as pH adjusting agent, medicinal liquid pH value is more stable, the more existing skill of breviscapine degradation material
Art is substantially reduced, and in the case of avoiding using other to increase the cosolvent of clinical practice risk, lamp has been satisfactorily addressed
Small cup florigen injection easily separates out tiny white point, white block, the problem of solution muddiness under the conditions of storage for a long time and winter low temperature.
The present invention solves the problems referred to above and be the technical scheme is that a kind of breviscapine drug injection preparation stability group
The preparation method of compound, comprises the steps:
(1) breviscapine 5g～100g, malic acid and/or natrium malicum 1mg～10mg are weighed；
(2) malic acid, natrium malicum are configured to the solution of 1g/100ml～10g/100ml respectively, standby；
(3), during breviscapine adds the water for injection 500ml of 30 DEG C～40 DEG C, stir to after being completely dissolved, the activated carbon of addition,
Described activated carbon dosage is 0.2g/100ml, stirs 15 minutes, filters decarburization；
(4) step (3) gained filtrate step (2) configures malic acid and/or natrium malicum solution regulation pH value be 6.0～
8.0, add the water for injection of less than 40 DEG C (30 DEG C～40 DEG C) to 1000ml；
(5) by step (4) gained medical filtration to clarification, fill, sterilizing, to obtain final product.
In described step (1) malic acid consumption be 1mg～2.0mg, natrium malicum consumption be 1mg～2.0mg.
Described step also includes osmotic pressure regulator 9.0g in (1).
Described osmotic pressure regulator is xylitol.
In such scheme, what addition malic acid and/or natrium malicum referred to addition can be in malic acid, natrium malicum
Any one, or malic acid, natrium malicum are with arbitrary proportion proportioning；In step (2), the malic acid of addition, natrium malicum
In one, then make a kind of solution, as included malic acid, natrium malicum two kinds, be configured to solution for standby the most respectively；Herba Erigerontis
Element, the consumption of osmotic pressure regulator can use the consumption of prior art, adjust according to the consumption of prior art.
In sum, the invention has the beneficial effects as follows: the present invention is by experimental studies have found that, at breviscapine drug injection
In preparation, when using malic acid, natrium malicum as pH adjusting agent, medicinal liquid pH value is more stable, and breviscapine degradation material is relatively
Prior art is substantially reduced, and in the case of avoiding using other to increase the cosolvent of clinical practice risk, solves satisfactorily
Breviscapini injection of having determined uses prior art products easily to separate out tiny white point, white block, solution muddiness in storage process
Problem, it is ensured that Breviscapini injection can be stable in storage process keeps the visible foreign matters detection symbol of injection
Close the regulation of drug standard, it is simple to clinical application and popularization.
The present invention passes through creative work, muddy to the tiny white point separated out in Breviscapini injection, white block, solution
Reason is analyzed and studies, and determines that deposit is mainly raw material free alkali crystallize and a small amount of catabolite, occurs above-mentioned former
Because of may with the pH value of solution and pH adjusting agent used by acid, alkali kind relevant.Therefore use natrium malicum as pH regulator
Agent, and use malic acid as pH value counter regulation agent, avoiding using the situation of the cosolvent of other increase clinical practice risks
Under, to solve, this product is easy under the conditions of storage for a long time and winter low temperature separates out tiny white point, white block, the problem of solution muddiness.
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 to this.
Embodiment 1:
The preparation method of a kind of breviscapine drug injection preparation stability compositions, comprises the steps: (1) weighting raw materials
With breviscapine extracting solution amount of calculation 25g, sodium chloride 7.0g, malic acid 2g, natrium malicum 4mg；(2) malic acid, natrium malicum
It is configured to the solution of 10%～20% respectively, standby；(3) adding in the water for injection 500ml of less than 40 DEG C, stirring is to being completely dissolved
After, add 0.02%(g/ml) activated carbon, stir 15 minutes, filtration decarburization；(4) filtrate malic acid or natrium malicum solution
Regulation pH value is 3.0～7.0, adds the water for injection of less than 40 DEG C to 1000ml；(5) medical filtration is to clarification, fill, goes out
Bacterium, to obtain final product.
Composition and the content thereof of the concrete each component of the present embodiment are as follows:
Breviscapine extracting solution 25g
Sodium chloride 7.0g
Malic acid 2.0g
Natrium malicum 4.0g
Malic acid, natrium malicum are configured to the solution of 10%～20% respectively, standby.Breviscapine extracting solution adds less than 40 DEG C
In water for injection 500ml, stir to after being completely dissolved, add the activated carbon (i.e. activated carbon dosage is 0.2g/100ml) of 0.15%,
Stir 15 minutes, filter decarburization.Filtrate malic acid or natrium malicum solution regulation pH value are 4.0～6.0, add less than 40 DEG C
Water for injection to 1000ml.Medical filtration, to clarification, fill, sterilizing, to obtain final product.
Embodiment 2:
The present embodiment another embodiment, as follows, the injection of above-mentioned raising breviscapine drug injection preparation stability
Pharmaceutical composition is prepared according to the following steps:
(1) weighting raw materials is with breviscapine amount of calculation 70g, malic acid 3g, natrium malicum 6g；(2) malic acid, natrium malicum divide
It is not configured to the solution of 10%～20%, standby；(3) adding in the water for injection 500ml of less than 40 DEG C, stirring is to being completely dissolved
After, add 0.15%(g/ml) activated carbon, stir 15 minutes, filtration decarburization；(4) filtrate malic acid or natrium malicum solution
Regulation pH value is 4.0～6.0, adds the water for injection of less than 40 DEG C to 1000ml；(5) medical filtration is to clarification, fill, goes out
Bacterium, to obtain final product.
Composition and the content thereof of the concrete each component of the present embodiment are as follows:
Breviscapine extracting solution 70g
Malic acid 3g
Natrium malicum 5g
Malic acid, natrium malicum are configured to the solution of 10%～20% respectively, standby.Hydrochloric acid breviscapine adds the note of less than 40 DEG C
Penetrate with in water 500ml, stir to after being completely dissolved, add the activated carbon (i.e. activated carbon dosage is 0.15g/100ml) of 0.15%,
Stir 15 minutes, filter decarburization.Filtrate malic acid or natrium malicum solution regulation pH value are 4.0～6.0, add less than 40 DEG C
Water for injection to 1000ml.Medical filtration, to clarification, fill, sterilizing, to obtain final product.
Embodiment 3:
Breviscapini injection stability comparative test
The visible foreign matters detection utilizing Breviscapini injection obtained by the present invention meets the regulation of drug standard, and solution
Stability is fine, in the case of avoiding using other to increase the cosolvent of clinical practice risk, solves breviscapine injection
Liquid easily occurs the problems such as small particles, white block, solution are muddy in storage process.The breviscapine obtained by the present invention is utilized to inject
Liquid is according to the related request of two annex Ⅺ Ⅹ C pharmaceutical preparation stability test guidelines of China's coastal port, respectively
Investigate to place to place for 24 months, 40 DEG C at 25 DEG C and within 6 months, 60 DEG C, placed 10 days, 0～5 DEG C of low temperature 20 days drug substance stable of placement
Property, result constant product quality at the conditions of the experiments described above, every Testing index all meets the regulation of this product quality standard.
The pharmacological results shows: utilize the stable Breviscapini injection obtained by the present invention without hemolytic, without mistake
Quick property, nonirritant, meet the requirement of drug administration by injection.
According to the above results, the breviscapine drug injection preparation of the present invention can improve Breviscapini injection
Clarity, particularly in the case of breviscapine injection period of storage is longer, it is possible to stable keeps the visible different of injection
Analyte detection meets the regulation of drug standard, solves breviscapine medicine and uses existing technical products longer in period of storage
In the case of the problem that small particles, white block, solution are muddy occurs, it is ensured that the visible foreign matters inspection of product meets drug quality mark
Accurate regulation, it is simple to clinical application and popularization.
As it has been described above, just can preferably realize the present invention.
Claims (4)
1. the preparation method of a breviscapine drug injection preparation stability compositions, it is characterised in that comprise the steps:
(1) breviscapine 5g～100g, malic acid and/or natrium malicum 1g～5g are weighed；
(2) malic acid, natrium malicum are configured to the solution of 1g/100ml～10g/100ml respectively, standby；
(3), during breviscapine adds the water for injection 500ml of 30 DEG C～40 DEG C, stir to after being completely dissolved, the activated carbon of addition,
Described activated carbon dosage is 0.15g/100ml, stirs 15 minutes, filters decarburization；
(4) step (3) gained filtrate step (2) configures malic acid and/or natrium malicum solution regulation pH value be 4.0～
6.0, add the water for injection of 30 DEG C～40 DEG C to 1000ml；
(5) by step (4) gained medical filtration to clarification, fill, sterilizing, to obtain final product.
The preparation method of a kind of breviscapine drug injection preparation stability compositions the most according to claim 1, it is special
Levy and be, in described step (1) malic acid consumption be 1g～5g, natrium malicum consumption be 1g～5g.
The preparation method of a kind of breviscapine drug injection preparation stability compositions the most according to claim 1, it is special
Levying and be, described step also includes osmotic pressure regulator 7.0g in (1).
The preparation method of a kind of breviscapine drug injection preparation stability compositions the most according to claim 3, it is special
Levying and be, described osmotic pressure regulator is sodium chloride.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078920A (en) * | 2018-02-27 | 2018-05-29 | 云南玉药生物制药有限公司 | A kind of Breviscapini injection preparation process of stabilization |
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| CN102008727A (en) * | 2010-12-07 | 2011-04-13 | 四川升和药业股份有限公司 | Injection-purpose medicine composition for improving stability of ligustrazine medicine injection formulation and preparation method of injection-purpose medicine composition |
| CN102188440A (en) * | 2010-03-16 | 2011-09-21 | 万生联合制药有限公司 | Preparation method of high-purity breviscapinun material used by breviscapinun injection |
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2016
- 2016-08-09 CN CN201610646230.4A patent/CN106214629A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101347429A (en) * | 2007-07-20 | 2009-01-21 | 重庆人本药物研究院 | Stable tartaric acid ifenprodil injection and method of preparing the same |
| CN102188440A (en) * | 2010-03-16 | 2011-09-21 | 万生联合制药有限公司 | Preparation method of high-purity breviscapinun material used by breviscapinun injection |
| CN102008727A (en) * | 2010-12-07 | 2011-04-13 | 四川升和药业股份有限公司 | Injection-purpose medicine composition for improving stability of ligustrazine medicine injection formulation and preparation method of injection-purpose medicine composition |
Non-Patent Citations (1)
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108078920A (en) * | 2018-02-27 | 2018-05-29 | 云南玉药生物制药有限公司 | A kind of Breviscapini injection preparation process of stabilization |
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