CN106389321A - Pharmaceutical composition capable of improving stability of Shenmai drug injection - Google Patents
Pharmaceutical composition capable of improving stability of Shenmai drug injection Download PDFInfo
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- CN106389321A CN106389321A CN201610968070.5A CN201610968070A CN106389321A CN 106389321 A CN106389321 A CN 106389321A CN 201610968070 A CN201610968070 A CN 201610968070A CN 106389321 A CN106389321 A CN 106389321A
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- Prior art keywords
- rhizoma zingiberis
- zingiberis recens
- injection
- pharmaceutical composition
- shenmai
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
-
- 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
-
- 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
-
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a pharmaceutical composition capable of improving the stability of a Shenmai drug injection. The pharmaceutical composition for injection is mainly prepared through the steps that salt of Shenmai is dissolved into water for injection, and oxalic acid and/or sodium oxalate is added to regulate the pH value of drug liquid by serving as a pH regulator, wherein the dosage of oxalic acid and/or sodium oxalate is 1 mg/100 ml-100.0 mg/100 ml. According to the pharmaceutical composition, the pH value of the injection is made to be more stable, and Shenmai degradation substances are greatly reduced compared with the prior art; on the condition that usage of other cosolvent capable of increasing clinical application risks is avoided, the clarity of the Shenmai injection is improved, and the problem that the Shenmai injection generates small white dots, white blocks and solution turbidity on the condition that the Shenmai injection is preserved for a long time by adopting a product in the prior art is particularly solved; it can be guaranteed that inspection of visible foreign matter of the product meets the regulations of a drug quality standard, and clinical medication and popularization are convenient.
Description
Technical field
A kind of the invention belongs to pharmaceutical technology field, in particular it relates to medicine improving Rhizoma Zingiberis Recens drug injection preparation stability
Compositions.
Background technology
Rhizoma Zingiberis Recens are the alkaloids extracting from chuanxiong, and chemical constitution is tetramethylpyazine, is a kind of novel agents of calcium ion
Antagonist, has blood circulation promoting and blood stasis dispelling, anti-platelet aggregation, excited medullary respiratory center and vasomotor center, expansion of blood vessels and props up
Tracheal smooth muscle, improve multiple effect such as microcirculation, be clinically used for for obliterated cerebral vascular disease such as incomplete brain blood supply, brain blood
Bolt formation, cerebral embolism and other ischemic angiopathys such as coronary heart disease, vasculitiss etc..The injection of Rhizoma Zingiberis Recens has been Chinese medicine
Modern hardly possible disease makes very big contribution.
Due to Rhizoma Zingiberis Recens dissolubility extreme difference in aqueous, therefore it is made into Rhizoma Zingiberis Recens hydrochlorate or Rhizoma Zingiberis Recens phosphate to increase
Its water solublity.Presently commercially available SHENMAI ZHUSHEYE mainly has the phosphatic injection with small volume of Rhizoma Zingiberis Recens hydrochlorate, Rhizoma Zingiberis Recens, Yi Ji
Glucose or sodium chloride is added to inject as the Large Copacity that osmotic pressure regulator is made in Rhizoma Zingiberis Recens hydrochlorate, Rhizoma Zingiberis Recens phosphate solution
Liquid.But when preparing above-mentioned injection it is necessary to the pH value of medicinal liquid is adjusted to the certain limit of suitable human injection's administration, at present
The pH value regulator that document report uses is sodium hydroxide solution or uses hydrochloric acid solution, phosphoric acid solution, but adopts above-mentioned pH
The SHENMAI ZHUSHEYE of value regulator preparation easily separates out tiny white point, white block, solution under the conditions of long-term storage and winter low temperature
The precipitate such as muddiness, cause the visible foreign matters check item of product unqualified.Prior art is to add polyoxyethylene sorbitan monoleate in the solution
As cosolvent, to solve product, the sedimentary problems such as small particles, white block, solution muddiness occur.But polyoxyethylene sorbitan monoleate due to
There is the effect of haemolysis and blood pressure lowering, and easily become sour in storage and autoclaving process, lead to the note containing polyoxyethylene sorbitan monoleate
Penetrate liquid clinical practice risk higher, make troubles to clinical application and popularization.
Content of the invention
The technical problem to be solved is to provide a kind of medicine group improving Rhizoma Zingiberis Recens drug injection preparation stability
Compound.This medicinal composition for injections adopts oxalic acid, Disodium oxalate. as pH adjusting agent, and is found using grass by creative work
When acid, Disodium oxalate. are as pH adjusting agent, medicinal liquid pH value is more stable, and Rhizoma Zingiberis Recens degradation material substantially reduces compared with prior art, is keeping away
In the case of exempting from the cosolvent using other increase clinical practice risks, SHENMAI ZHUSHEYE is satisfactorily addressed and has store long-term
Deposit with winter low temperature under the conditions of easily separate out the muddy problem of tiny white point, white block, solution.
The present invention solves the above problems and be employed technical scheme comprise that：A kind of raising Rhizoma Zingiberis Recens drug injection preparation stability
Pharmaceutical composition, is mainly dissolved in water for injection by the salt of Rhizoma Zingiberis Recens, adds osmotic pressure regulator, and adds oxalic acid and/or Disodium oxalate.
The medicinal composition for injections made as pH adjusting agent regulating liquid medicine pH value, the consumption of described oxalic acid and/or Disodium oxalate. is 1mg
～100.0mg/100ml.
Described osmotic pressure regulator is glucose, sodium chloride, xylitol, Mannitol, any one or a few in Fructose.
The consumption of osmotic pressure regulator is prior art, and sodium chloride consumption is 0.9g/100ml；Glucose, xylitol, Mannitol, Fructose
Consumption is 5g/100ml～10g/100ml.
The salt of described Rhizoma Zingiberis Recens includes Rhizoma Zingiberis Recens hydrochlorate, Rhizoma Zingiberis Recens phosphate.
The concentration of the salt of described Rhizoma Zingiberis Recens is calculated as 0.1g～10g/100ml with Rhizoma Zingiberis Recens.
Described medicinal liquid pH value is 4.0～7.0.
Described Rhizoma Zingiberis Recens drug injection preparation formulation is injection.
The preparation method of the medicinal composition for injections of above-mentioned raising Rhizoma Zingiberis Recens drug injection preparation stability, including following steps
Suddenly：
(1) salt weighing Rhizoma Zingiberis Recens is with Rhizoma Zingiberis Recens amount of calculation 0.1g～100g, oxalic acid and/or Disodium oxalate. 2mg～4.0g；
(2) oxalic acid, Disodium oxalate. are configured to the solution of 10g/100ml～20g/100ml respectively, standby；
(3) salt of Rhizoma Zingiberis Recens, sodium chloride add in 30 DEG C～40 DEG C of water for injection 500ml, stir to after be completely dissolved, plus
The activated carbon entering, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filters decarburization；
(4) step (3) gained filtrate step (2) configures oxalic acid and/or sodium oxalate solution adjust pH value be 3.0～
7.0, the water for injection adding less than 40 DEG C (30 DEG C～40 DEG C) is to 1000ml；
(5) by step (4) gained medical filtration to clarification, fill, sterilizing, obtain final product.
Described step (1) mesoxalic acid consumption is 1mg～2.0g, Disodium oxalate. consumption is 1mg～2.0g.
Osmotic pressure regulator 9.0g is also included in described step (1).
Described osmotic pressure regulator is sodium chloride.
In such scheme, add that oxalic acid and/or Disodium oxalate. refer to add can be oxalic acid, any one in Disodium oxalate.,
Or oxalic acid, Disodium oxalate. are with arbitrary proportion proportioning；In step (2), one of the oxalic acid of addition, Disodium oxalate., then make
A kind of solution, such as includes oxalic acid, two kinds of Disodium oxalate., is then configured to solution for standby respectively；The salt of Rhizoma Zingiberis Recens, the use of osmotic pressure regulator
Amount can adopt the consumption of prior art, according to the consumption adjustment of prior art.
In sum, the invention has the beneficial effects as follows：The present invention pass through experimental studies have found that, in Rhizoma Zingiberis Recens drug injection preparation
In, during using oxalic acid, Disodium oxalate. as pH adjusting agent, medicinal liquid pH value is more stable, and Rhizoma Zingiberis Recens degradation material is compared with prior art significantly
Reduce, in the case of avoiding increasing the cosolvent of clinical practice risk using other, injection containing ginseng extract has been satisfactorily addressed
Liquid adopts prior art products easily to separate out the problem of tiny white point, white block, solution muddiness in storage process it is ensured that joining
Wheat injection can be stable in storage process the visible foreign matters detection of holding injection meet the regulation of drug standard,
It is easy to clinical application and popularization.
The present invention passes through creative work, the reason muddy to the tiny white point separating out in SHENMAI ZHUSHEYE, white block, solution
It is analyzed and studies, determine that deposit is mainly raw material free alkali crystallize and a small amount of catabolite, above-mentioned reason can
Can be relevant with species sour, alkali used by the pH value of solution and pH adjusting agent.Disodium oxalate. is therefore used as pH adjusting agent, and makes
With oxalic acid as pH value counter regulation agent, in the case of avoiding increasing the cosolvent of clinical practice risk using other, to solve
This product muddy problem of the tiny white point of easy precipitation, white block, solution under the conditions of long-term storage and winter low temperature.
Specific embodiment
With reference to embodiment, the present invention is described in further detail, but embodiments of the present invention not limited to this.
Embodiment 1
A kind of preparation method of the pharmaceutical composition improving Rhizoma Zingiberis Recens drug injection preparation stability, comprises the steps：(1)
Weigh crude drug with Rhizoma Zingiberis Recens amount of calculation 0.1g～100g, sodium chloride 9.0g, oxalic acid 1mg～2.0g, Disodium oxalate. 1mg～2.0g；(2)
Oxalic acid, Disodium oxalate. are configured to 10%～20% solution respectively, standby.(3) add in less than 40 DEG C of water for injection 500ml,
Stir to after be completely dissolved, add the activated carbon of 0.02% (g/ml), stir 15 minutes, filter decarburization.(4) filtrate oxalic acid or
It is 3.0～7.0 that sodium oxalate solution adjusts pH value, adds less than 40 DEG C of water for injection to 1000ml；(5) medical filtration is extremely clear
Clearly, fill, sterilizing, obtain final product.
Specifically the composition of each component and its content are as follows for the present embodiment：
Oxalic acid, Disodium oxalate. are configured to 10%～20% solution respectively, standby.Hydrochloric acid Rhizoma Zingiberis Recens, sodium chloride add 40 DEG C with
Under water for injection 500ml in, stir to after be completely dissolved, add 0.02% activated carbon (i.e. activated carbon dosage be 0.02g/
100ml), stir 15 minutes, filter decarburization.Filtrate oxalic acid or sodium oxalate solution adjust pH value for 3.8～4.2, add 40 DEG C
Following water for injection is to 1000ml.Medical filtration, to clarification, fill, sterilizing, obtains final product.
Embodiment 2
Or, the medicinal composition for injections of above-mentioned raising Rhizoma Zingiberis Recens drug injection preparation stability is prepared according to the following steps：
(1) weigh crude drug with Rhizoma Zingiberis Recens amount of calculation 0.1g～100g, oxalic acid 1mg～2.0g, Disodium oxalate. 1mg～2.0g；(2)
Oxalic acid, Disodium oxalate. are configured to 10%～20% solution respectively, standby.(3) add in less than 40 DEG C of water for injection 500ml,
Stir to after be completely dissolved, add the activated carbon of 0.02% (g/ml), stir 15 minutes, filter decarburization.(4) filtrate oxalic acid or
It is 3.0～7.0 that sodium oxalate solution adjusts pH value, adds less than 40 DEG C of water for injection to 1000ml；(5) medical filtration is extremely clear
Clearly, fill, sterilizing, obtain final product.
Specifically the composition of each component and its content are as follows for the present embodiment：
Hydrochloric acid Rhizoma Zingiberis Recens 20g
Oxalic acid 1.0g
Disodium oxalate. 2.0g
Oxalic acid, Disodium oxalate. are configured to 10%～20% solution respectively, standby.Hydrochloric acid Rhizoma Zingiberis Recens add less than 40 DEG C of injection
With in water 500ml, stirring to after be completely dissolved, add 0.02% activated carbon (i.e. activated carbon dosage is 0.02g/100ml), stir
Mix 15 minutes, filter decarburization.Filtrate oxalic acid or sodium oxalate solution adjust pH value for 3.8～4.2, add less than 40 DEG C of injection
With water to 1000ml.Medical filtration, to clarification, fill, sterilizing, obtains final product.
Embodiment 3
Rhizoma Zingiberis Recens sodium chloride injection stability comparative test
Visible foreign matters detection using Rhizoma Zingiberis Recens sodium chloride injection obtained by the present invention meets the regulation of drug standard,
And stability of solution is very well, in the case of avoiding increasing the cosolvent of clinical practice risk using other, solve Rhizoma Zingiberis Recens chlorine
Change sodium injection and the problems such as small particles, white block, solution muddiness easily occurs in storage process.Using the Rhizoma Zingiberis Recens obtained by the present invention
Sodium chloride injection is according to the correlation of two annex of China's coastal port Ⅺ Ⅹ C pharmaceutical preparation stability test guideline
Require, investigated respectively 25 DEG C place place within 24 months, 40 DEG C place within 6 months, 60 DEG C 10 days, 0～5 DEG C of low temperature places 20 days
Medicine stability, product quality is stable at the conditions of the experiments described above for result, and every Testing index all meets this product quality standard
Regulation.
The pharmacological results show：Using the no hemolytic, no of the stable Rhizoma Zingiberis Recens sodium chloride injection obtained by the present invention
Anaphylaxis, nonirritant, meet the requirement of drug administration by injection.
1 25 DEG C of study on the stability results of table
Table 2 60 DEG C of study on the stability results of hydrochloric acid Rhizoma Zingiberis Recens sodium chloride injection
3 40 DEG C of study on the stability results of table
4 0～5 DEG C of low temperature visible foreign matters of table investigate result
According to the above results, the Rhizoma Zingiberis Recens drug injection preparation of the present invention can improve the clarity of SHENMAI ZHUSHEYE,
Particularly in the case that injection containing ginseng extract period of storage is longer, the visible foreign matters detection of holding injection that can be stable meets medicine
The regulation of quality standard, solves Rhizoma Zingiberis Recens medicine and little Bai using existing technical products in the case that period of storage is longer
The muddy problem of point, white block, solution, it is ensured that the visible foreign matters inspection of product meets the regulation of drug standard, is easy to
Clinical application and popularization.
As described above, just can preferably realize the present invention.
Claims (6)
1. a kind of pharmaceutical composition improving Rhizoma Zingiberis Recens drug injection preparation stability is it is characterised in that mainly molten by the salt of Rhizoma Zingiberis Recens
In water for injection, add the medicinal composition for injections that oxalic acid and/or Disodium oxalate. are made as pH adjusting agent regulating liquid medicine pH value,
The consumption of described oxalic acid and/or Disodium oxalate. is 1mg～100.0mg/100ml.
2. a kind of pharmaceutical composition improving Rhizoma Zingiberis Recens drug injection preparation stability according to claim 1, its feature exists
In, also include osmotic pressure regulator, described osmotic pressure regulator is glucose, sodium chloride, xylitol, Mannitol, in Fructose
Any one or a few.
3. a kind of pharmaceutical composition improving Rhizoma Zingiberis Recens drug injection preparation stability according to claim 1, its feature exists
In the salt of described Rhizoma Zingiberis Recens includes Rhizoma Zingiberis Recens hydrochlorate, Rhizoma Zingiberis Recens phosphate.
4. the pharmaceutical composition of a kind of raising Rhizoma Zingiberis Recens drug injection preparation stability according to claim 1 or 3, its feature
It is, the concentration of the salt of described Rhizoma Zingiberis Recens is calculated as 0.1g～10g/100ml with Rhizoma Zingiberis Recens.
5. a kind of pharmaceutical composition improving Rhizoma Zingiberis Recens drug injection preparation stability according to claim 1, its feature exists
In described medicinal liquid pH value is 4.0～7.0.
6. a kind of pharmaceutical composition improving Rhizoma Zingiberis Recens drug injection preparation stability according to claim 1, its feature exists
In described Rhizoma Zingiberis Recens drug injection preparation formulation is injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610968070.5A CN106389321A (en) | 2016-11-06 | 2016-11-06 | Pharmaceutical composition capable of improving stability of Shenmai drug injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610968070.5A CN106389321A (en) | 2016-11-06 | 2016-11-06 | Pharmaceutical composition capable of improving stability of Shenmai drug injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106389321A true CN106389321A (en) | 2017-02-15 |
Family
ID=58014346
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610968070.5A Withdrawn CN106389321A (en) | 2016-11-06 | 2016-11-06 | Pharmaceutical composition capable of improving stability of Shenmai drug injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106389321A (en) |
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2016
- 2016-11-06 CN CN201610968070.5A patent/CN106389321A/en not_active Withdrawn
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Application publication date: 20170215 |