CN107823130A - A kind of preparation method of tetrandrine injection agent medicine composition - Google Patents
A kind of preparation method of tetrandrine injection agent medicine composition Download PDFInfo
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- CN107823130A CN107823130A CN201711251690.8A CN201711251690A CN107823130A CN 107823130 A CN107823130 A CN 107823130A CN 201711251690 A CN201711251690 A CN 201711251690A CN 107823130 A CN107823130 A CN 107823130A
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- Prior art keywords
- tetrandrine
- injection
- preparation
- salicylic acid
- sodium salicylate
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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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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4748—Quinolines; Isoquinolines forming part of bridged ring systems
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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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- General Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of tetrandrine injection agent medicine composition, the medicinal composition for injections is mainly dissolved in water for injection by the salt of tetrandrine, salicylic acid and/or sodium salicylate are added as medicinal composition for injections made of pH adjusting agent regulating liquid medicine pH value, the dosage of the salicylic acid and/or sodium salicylate is 0.1mg~200.0mg/100ml.The present invention can make the parenteral solution pH value more stable, tetrandrine degradation material substantially reduces compared with prior art, in the case where avoiding the cosolvent using other increase clinical practice risks, improve the clarity of tetrandrine parenteral solution, particularly solve the problems, such as that tetrandrine parenteral solution occurs small particles, white block, solution muddiness in the case where period of storage is longer using prior art products, it can ensure that the visible foreign matters inspection of product meets the regulation of drug standard, be easy to clinical application and popularization.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to a kind of system of tetrandrine injection agent medicine composition
Preparation Method.
Background technology
Tetrandrine is also known as tetrandrine, once claims Tet, tetrandrine A prime.For a kind of bimolecular with oxygen bridge
Benzyl morphinane alkaloid, molecular formula C38H42N2O6.1932 are close on flat three Lang Shouxian of rattan obtains from the arch root that falls down to the ground.The Chinese is prevented
Own alkali is acicular crystal, 217~218 DEG C of fusing point.With analgesia and antiinflammation, analgesic effect is the 13% of morphine, and anti-inflammatory is made
It is similar with to examining pine.Tetrandrine has preferable therapeutic effect to high blood pressure, especially suitable for severe hypertension.Stephania tetrandra
The quaternary ammonium salt (iodide) of alkali is referred to as tetrandrine dimethiodide, there is relaxed muscle effect, is once used to supervise bed.
Due to tetrandrine dissolubility extreme difference, therefore be made into tetrandrine hydrochloride or tetrandrine in aqueous
Phosphate is water-soluble to increase it.Presently commercially available tetrandrine parenteral solution mainly has tetrandrine hydrochloride, tetrandrine phosphorus
The injection with small volume of hydrochlorate, and glucose or phosphoric acid are added in tetrandrine hydrochloride, tetrandrine phosphate solution
Sodium dihydrogen is as high-capacity injection made of osmotic pressure regulator.But when preparing above-mentioned parenteral solution, it is necessary to by the pH of decoction
To the certain limit for being adapted to human injection's administration, the pH value regulator that document report uses at present is that sodium hydroxide is molten for value regulation
Liquid is stored using hydrochloric acid solution, phosphoric acid solution, but using the tetrandrine parenteral solution of above-mentioned pH value regulator preparation for a long time
With the sediments such as tiny white point, white block, solution muddiness are easily separated out under the conditions of winter low temperature, cause the visible foreign matters inspection of product
Item is unqualified.It now yet there are no preferable solution.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of preparation side of tetrandrine injection agent medicine composition
Method.
The medicinal composition for injections is sent out using salicylic acid, sodium salicylate as pH adjusting agent, and by creative work
During now using salicylic acid, sodium salicylate as pH adjusting agent, decoction pH value is more stable, the more existing skill of tetrandrine degradation material
Art substantially reduces, and in the case where avoiding the cosolvent using other increase clinical practice risks, the Chinese has been satisfactorily addressed
The problem of menispermine parenteral solution easily separates out tiny white point, white block, solution muddiness under the conditions of long-term storage and winter low temperature.
Technical scheme is used by the present invention solves the above problems：A kind of tetrandrine injection agent medicine composition
Preparation method, comprise the steps：
(1) salt of tetrandrine is weighed with tetrandrine amount of calculation 0.1g~100g, salicylic acid and/or sodium salicylate 2mg
~4.0g；
(2) salicylic acid, sodium salicylate are configured to 10g/100ml~20g/100ml solution respectively, standby；
(3) salt of tetrandrine, sodium dihydrogen phosphate are added in 30 DEG C~40 DEG C of water for injection 500ml, are stirred to complete
After dissolving, the activated carbon of addition, the activated carbon dosage is 0.02g/100ml, is stirred 15 minutes, filters decarburization；
(4) salicylic acid of filtrate step (2) configuration obtained by step (3) and/or sodium salicylate solution regulation pH value are 3.0
~7.0, the water for injection of less than 40 DEG C (30 DEG C~40 DEG C) is added to 1000ml；
(5) it is filling by medical filtration obtained by step (4) to clarification, sterilizing, produce.
In the step (1) salicylic acid dosage be 1mg~2.0g, sodium salicylate dosage be 1mg~2.0g.
Also include osmotic pressure regulator 9.0g in the step (1).
The osmotic pressure regulator is sodium dihydrogen phosphate.
In such scheme, add that salicylic acid and/or sodium salicylate refer to add can be in salicylic acid, sodium salicylate
It is any, or salicylic acid, sodium salicylate match with arbitrary proportion；In step (2), salicylic acid, the sodium salicylate of addition
In one kind, then a kind of solution is made, such as include salicylic acid, two kinds of sodium salicylate, then be configured to solution for standby respectively；Stephania tetrandra
The salt of alkali, the dosage of osmotic pressure regulator can use the dosage of prior art, be adjusted according to the dosage of prior art.
In summary, the beneficial effects of the invention are as follows：The present invention by experimental studies have found that, in tetrandrine drug injection
In preparation, during using salicylic acid, sodium salicylate as pH adjusting agent, decoction pH value is more stable, tetrandrine degradation material compared with
Prior art substantially reduces, and in the case where avoiding the cosolvent using other increase clinical practice risks, satisfactorily solves
Tetrandrine parenteral solution of having determined easily separates out tiny white point, white block, solution muddiness using prior art products in storage process
The problem of, it is ensured that the visible foreign matters detection symbol for the holding parenteral solution that tetrandrine parenteral solution can be stablized in storage process
The regulation of drug standard is closed, is easy to clinical application and popularization.
The present invention is muddy to the tiny white point, white block, solution that are separated out in tetrandrine parenteral solution by creative work
Reason is analyzed and studied, and it is mainly raw material free alkali crystallization and a small amount of catabolite to determine deposit, above-mentioned original occurs
Because may with the pH value and pH adjusting agent of solution used in acid, alkali species it is relevant.Therefore sodium salicylate is used to be adjusted as pH
Agent, and salicylic acid is used as pH value counter regulation agent, in the situation for avoiding the cosolvent using other increase clinical practice risks
Under, to solve the problems, such as that this product easily separates out tiny white point, white block, solution muddiness under the conditions of long-term storage and winter low temperature.
Embodiment
With reference to embodiment, the present invention is described in further detail, but the implementation of the present invention is not limited to this.
Embodiment 1
A kind of preparation method for the medicinal composition for injections for improving tetrandrine drug injection preparation stability, including under
State step：(1) weigh bulk drug with tetrandrine amount of calculation 0.1g~100g, sodium dihydrogen phosphate 9.0g, salicylic acid 1mg~
2.0g, sodium salicylate 1mg~2.0g；(2) salicylic acid, sodium salicylate are configured to 10%~20% solution respectively, standby.(3)
Add in less than 40 DEG C of water for injection 500ml, stir to after being completely dissolved, add 0.02% (g/ml) activated carbon, stirring
15 minutes, filter decarburization.(4) filtrate water poplar acid or sodium salicylate solution regulation pH value are 3.0~7.0, add less than 40 DEG C
Water for injection to 1000ml；(5) medical filtration is extremely clarified, filling, sterilizing, is produced.
The composition and its content of the specific each component of the present embodiment are as follows：
Salicylic acid, sodium salicylate are configured to 10%~20% solution respectively, standby.Berbamine Hydrochloride, biphosphate
Sodium is added in less than 40 DEG C of water for injection 500ml, is stirred to after being completely dissolved, is added 0.02% activated carbon (i.e. activated carbon
Dosage is 0.02g/100ml), stir 15 minutes, filter decarburization.Filtrate water poplar acid or sodium salicylate solution regulation pH value are
3.8~4.2, less than 40 DEG C of water for injection is added to 1000ml.Medical filtration is extremely clarified, filling, sterilizing, is produced.
Embodiment 2
Or the medicinal composition for injections of above-mentioned raising tetrandrine drug injection preparation stability is made in the steps below
It is standby：
(1) weigh bulk drug with tetrandrine amount of calculation 0.1g~100g, salicylic acid 1mg~2.0g, sodium salicylate 1mg~
2.0g；(2) salicylic acid, sodium salicylate are configured to 10%~20% solution respectively, standby.(3) less than 40 DEG C of injection is added
With in water 500ml, stir to after being completely dissolved, add 0.02% (g/ml) activated carbon, stir 15 minutes, filter decarburization.(4)
Filtrate water poplar acid or sodium salicylate solution regulation pH value are 3.0~7.0, add less than 40 DEG C of water for injection to 1000ml；
(5) medical filtration is extremely clarified, filling, sterilizing, is produced.
The composition and its content of the specific each component of the present embodiment are as follows：
Berbamine Hydrochloride 20g
Salicylic acid 1.0g
Sodium salicylate 2.0g
Salicylic acid, sodium salicylate are configured to 10%~20% solution respectively, standby.Berbamine Hydrochloride add 40 DEG C with
Under water for injection 500ml in, stir to after being completely dissolved, adding 0.02% activated carbon, (i.e. activated carbon dosage is 0.02g/
100ml), stir 15 minutes, filter decarburization.Filtrate water poplar acid or sodium salicylate solution regulation pH value are 3.8~4.2, are added
Less than 40 DEG C of water for injection is to 1000ml.Medical filtration is extremely clarified, filling, sterilizing, is produced.
Embodiment 3
Tetrandrine biphosphate sodium injection stability comparative test
Meet drug quality mark using the visible foreign matters detection of tetrandrine biphosphate sodium injection obtained by the present invention
Accurate regulation, and stability of solution is fine, in the case where avoiding the cosolvent using other increase clinical practice risks, solves
Easily there is the problems such as small particles, white block, solution muddiness in storage process in tetrandrine biphosphate sodium injection.Utilize this
The obtained tetrandrine biphosphate sodium injection of invention is according to the C pharmaceutical preparations of two annex of China's coastal port Ⅺ Ⅹ
The related request of stability test guideline, investigate to place to place 6 months, 60 DEG C for 24 months, 40 DEG C at 25 DEG C respectively and put
10 days, 0~5 DEG C of low temperature 20 days medicine stability of placement are put, as a result product quality is stable at the conditions of the experiments described above, items detection
Index meets the regulation of this product quality standard.
The Pharmacological experiment result shows that：Using the tetrandrine biphosphate sodium injection of the stabilization obtained by the present invention without molten
It is courageous and upright, without anaphylaxis, nonirritant, meet the requirement of drug administration by injection.
1 25 DEG C of study on the stability results of table
The 60 DEG C of study on the stability results of Berbamine Hydrochloride biphosphate sodium injection of table 2
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
It can be seen from the above results, tetrandrine drug injection preparation of the invention can improve tetrandrine parenteral solution
Clarity, particularly in the case where tetrandrine injection period of storage is longer, what can be stablized keeps the visible different of parenteral solution
Analyte detection meets the regulation of drug standard, and it is longer in period of storage using existing technical products to solve tetrandrine medicine
In the case of there is the problem of small particles, white block, solution muddiness, it is ensured that the visible foreign matters inspection of product meets drug quality mark
Accurate regulation, is easy to clinical application and popularization.
As described above, it can preferably realize the present invention.
Claims (5)
1. a kind of preparation method of tetrandrine injection agent medicine composition, it is characterised in that comprise the steps：
（1）Weigh the salt of tetrandrine with tetrandrine amount of calculation 0.1g~100g, salicylic acid and/or sodium salicylate 2mg~
4.0g；
（2）Salicylic acid, sodium salicylate are configured to 10g/100ml~20g/100ml solution respectively, standby；
（3）The salt of tetrandrine, sodium dihydrogen phosphate are added in 30 DEG C~40 DEG C of water for injection 500ml, and stirring is to being completely dissolved
Afterwards, the activated carbon of addition, the activated carbon dosage are 0.02g/100ml, are stirred 15 minutes, filter decarburization；
（4）Step（3）Gained filtrate step（2）Configuration salicylic acid and/or sodium salicylate solution regulation pH value be 3.0~
7.0, less than 40 DEG C of water for injection is added to 1000ml；
（5）By step（4）Gained medical filtration is extremely clarified, filling, sterilizing, is produced.
A kind of 2. preparation method of tetrandrine injection agent medicine composition according to claim 1, it is characterised in that
The step（1）Middle salicylic acid dosage is 1mg~2.0g, sodium salicylate dosage is 1mg~2.0g.
3. a kind of preparation method of tetrandrine injection agent medicine composition according to claim 1 or 2, its feature exist
In the step（1）In also include osmotic pressure regulator 9.0g.
A kind of 4. preparation method of tetrandrine injection agent medicine composition according to claim 3, it is characterised in that
The osmotic pressure regulator is sodium dihydrogen phosphate.
A kind of 5. preparation method of tetrandrine injection agent medicine composition according to claim 1, it is characterised in that
The tetrandrine drug injection preparation formulation is parenteral solution.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711251690.8A CN107823130A (en) | 2017-12-01 | 2017-12-01 | A kind of preparation method of tetrandrine injection agent medicine composition |
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| CN201711251690.8A CN107823130A (en) | 2017-12-01 | 2017-12-01 | A kind of preparation method of tetrandrine injection agent medicine composition |
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| CN107823130A true CN107823130A (en) | 2018-03-23 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110680802A (en) * | 2019-11-11 | 2020-01-14 | 江西银涛药业有限公司 | Tetrandrine injection and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106361969A (en) * | 2016-11-06 | 2017-02-01 | 成都先先先生物科技有限公司 | Preparation method of drug composition for improving stability of Shengmai drug injection preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106361969A (en) * | 2016-11-06 | 2017-02-01 | 成都先先先生物科技有限公司 | Preparation method of drug composition for improving stability of Shengmai drug injection preparation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110680802A (en) * | 2019-11-11 | 2020-01-14 | 江西银涛药业有限公司 | Tetrandrine injection and preparation method thereof |
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Application publication date: 20180323 |