CN106361693A - Preparation method of leech injection preparation pharmaceutical composition - Google Patents
Preparation method of leech injection preparation pharmaceutical composition Download PDFInfo
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- CN106361693A CN106361693A CN201610968059.9A CN201610968059A CN106361693A CN 106361693 A CN106361693 A CN 106361693A CN 201610968059 A CN201610968059 A CN 201610968059A CN 106361693 A CN106361693 A CN 106361693A
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- Prior art keywords
- injection
- hirudo
- preparation
- maleic acid
- leech
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- 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 preparation method of a leech injection preparation pharmaceutical composition. The injection pharmaceutical composition is an injection pharmaceutical composition which is obtained through dissolving salt of leeches into injection water and adding maleic acid and/or sodium maleate as a pH (Potential of Hydrogen) regulation agent to adjust the pH value of medicine liquid; the use amount of the maleic acid and/or the sodium maleate is 0.1mg/100ml to 200.0mg/100ml. According to the preparation method of the leech injection preparation pharmaceutical composition, the pH value of injection liquid can be more stable; compared with the prior art, the content of leech degraded substances is greatly reduced; the clarity of the leech injection liquid is improved under the condition that other co-solvents, which increase clinical application risks, are not used; the problems that the leech injection liquid adopts a product in the prior art and then has small white points and white blocks, and a solution is turbid under the condition that storage time is relatively long are especially solved; the inspection of visible foreign matters of a product can accord with specifications of medicine quality standards and clinical medicine administration and popularization are facilitated.
Description
Technical field
A kind of the invention belongs to pharmaceutical technology field, in particular it relates to preparation side of Hirudo injection agent medicine compositionss
Method.
Background technology
Hirudo is the alkaloid 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 Hirudo has been Chinese medicine
Modern hardly possible disease makes very big contribution.
Due to Hirudo dissolubility extreme difference in aqueous, therefore it is made into Hirudo hydrochlorate or Hirudo phosphate to increase
Its water solublity.Presently commercially available leech injection mainly has the phosphatic injection with small volume of Hirudo hydrochlorate, Hirudo, Yi Ji
Glucose or sodium chloride is added to inject as the Large Copacity that osmotic pressure regulator is made in Hirudo hydrochlorate, Hirudo 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 leech injection 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 preparation method of Hirudo injection agent medicine compositionss.
This medicinal composition for injections adopts maleic acid, Monosodium maleate is as ph regulator, and is sent out by creative work
When now adopting maleic acid, Monosodium maleate as ph regulator, medicinal liquid ph value is more stable, and Hirudo degradation material is big compared with prior art
Big reduction, in the case of avoiding increasing the cosolvent of clinical practice risks using other, has been satisfactorily addressed Hirudo note
Penetrate liquid muddy problem of the tiny white point of easy precipitation, white block, solution under the conditions of long-term storage and winter low temperature.
The present invention solves the above problems a kind of preparation of employed technical scheme comprise that Hirudo injection agent medicine compositionss
Method, is mainly dissolved in water for injection by the salt of Hirudo, adds osmotic pressure regulator, and adds maleic acid and/or Monosodium maleate to make
The medicinal composition for injections made for ph regulator regulating liquid medicine ph value, the consumption of described maleic acid and/or Monosodium maleate is
0.1mg～200.0mg/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 Hirudo includes Hirudo hydrochlorate, Hirudo phosphate.
The concentration of the salt of described Hirudo is calculated as 10mg～10g/100ml with Hirudo.
Described medicinal liquid ph value is 3.0～6.0.
Described Hirudo drug injection preparation formulation is injection.
A kind of preparation method of above-mentioned Hirudo injection agent medicine compositionss, comprises the steps:
(1) salt weighing Hirudo is with Hirudo amount of calculation 0.1g～100g, maleic acid and/or Monosodium maleate 2mg～4.0g；
(2) maleic acid, Monosodium maleate are configured to the solution of 10g/100ml～20g/100ml respectively, standby；
(3) salt of Hirudo, 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) maleic acid that step (3) gained filtrate step (2) configures and/or Monosodium maleate solution regulation ph value are 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.
In described step (1) maleic acid consumption be 1mg～2.0g, Monosodium maleate consumption be 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 maleic acid and/or Monosodium maleate refer to add can be maleic acid, in Monosodium maleate
Any one, or maleic acid, Monosodium maleate are with arbitrary proportion proportioning；In step (2), the maleic acid of addition, Monosodium maleate
One of, then make a kind of solution, such as include maleic acid, two kinds of Monosodium maleate, be then configured to solution for standby respectively；Hirudo
Salt, the consumption of osmotic pressure regulator 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 Hirudo drug injection preparation
In, during using maleic acid, Monosodium maleate as ph regulator, medicinal liquid ph value is more stable, and Hirudo degradation material is compared with prior art
Substantially reduce, in the case of avoiding increasing the cosolvent of clinical practice risk using other, Hirudo has been satisfactorily addressed
Injection adopts prior art products easily to separate out tiny white point, white block, the problem of solution muddiness, Ke Yibao in storage process
The visible foreign matters detection demonstrate,proving the holding injection that leech injection can be stable in storage process meets drug standard
Regulation, 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 leech injection, 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 regulator.Monosodium maleate is therefore used as ph regulator, and
Maleic acid is used as ph value counter regulation agent, in the case of avoiding increasing the cosolvent of clinical practice risk using other, with
Easily the tiny white point of precipitation, white block, solution are muddy under the conditions of long-term storage and winter low temperature to solve the problems, such as this product.
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 Hirudo injection agent medicine compositionss, comprises the steps: that (1) weighs crude drug with Hirudo
Amount of calculation 0.1g～100g, sodium chloride 9.0g, maleic acid 1mg～2.0g, Monosodium maleate 1mg～2.0g；(2) maleic acid, Malaysia
Sour sodium is configured to 10%～20% solution respectively, standby.(3) add in less than 40 DEG C of water for injection 500ml, stir to complete
After CL, add the activated carbon of 0.02% (g/ml), stir 15 minutes, filter decarburization.(4) filtrate maleic acid or maleic acid
It is 3.0～7.0 that sodium solution adjusts ph value, adds less than 40 DEG C of water for injection to 1000ml；(5) medical filtration, to clarifying, fills
Dress, sterilizing, obtain final product.
Specifically the composition of each component and its content are as follows for the present embodiment:
Maleic acid, Monosodium maleate are configured to 10%～20% solution respectively, standby.Hydrochloric acid Hirudo, sodium chloride add 40
In water for injection 500ml below DEG C, stir to after be completely dissolved, (i.e. activated carbon dosage is the activated carbon of addition 0.02%
0.02g/100ml), stir 15 minutes, filter decarburization.Filtrate maleic acid or Monosodium maleate solution adjust ph value for 3.8～
4.2, add less than 40 DEG C of water for injection to 1000ml.Medical filtration, to clarification, fill, sterilizing, obtains final product.
Embodiment 2
Or, a kind of above-mentioned preparation method of Hirudo injection agent medicine compositionss is prepared according to the following steps:
(1) weigh crude drug with Hirudo amount of calculation 0.1g～100g, maleic acid 1mg～2.0g, Monosodium maleate 1mg～
2.0g；(2) maleic acid, Monosodium maleate are configured to 10%～20% solution respectively, standby.(3) add less than 40 DEG C of injection
With in water 500ml, stirring to after be completely dissolved, add the activated carbon of 0.02% (g/ml), stir 15 minutes, filter decarburization.(4)
It is 3.0～7.0 that filtrate maleic acid or Monosodium maleate solution adjust ph value, adds less than 40 DEG C of water for injection to 1000ml；
(5) medical filtration, to clarification, fill, sterilizing, obtains final product.
Specifically the composition of each component and its content are as follows for the present embodiment:
Hydrochloric acid Hirudo 20g
Maleic acid 1.0g
Monosodium maleate 2.0g
Maleic acid, Monosodium maleate are configured to 10%～20% solution respectively, standby.Hydrochloric acid Hirudo adds less than 40 DEG C
In water for injection 500ml, stir to after be completely dissolved, (i.e. activated carbon dosage is 0.02g/ to the activated carbon of addition 0.02%
100ml), stir 15 minutes, filter decarburization.Filtrate maleic acid or Monosodium maleate solution regulation ph value are 3.8～4.2, add
Less than 40 DEG C of water for injection is to 1000ml.Medical filtration, to clarification, fill, sterilizing, obtains final product.
Embodiment 3
Hirudo sodium chloride injection stability comparative test
Visible foreign matters detection using Hirudo 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 Hirudo chlorine
Change sodium injection and the problems such as small particles, white block, solution muddiness easily occurs in storage process.Using the Hirudo obtained by the present invention
Sodium chloride injection is according to the correlation of two annex c pharmaceutical preparation stability test guidelines of China's coastal port
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 Hirudo 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 Hirudo 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 Hirudo drug injection preparation of the present invention can improve the clarity of leech injection,
Particularly in the case that Hirudo injection 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 Hirudo 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 (5)
1. a kind of preparation method of Hirudo injection agent medicine compositionss is it is characterised in that comprise the steps:
(1) salt weighing Hirudo is with Hirudo amount of calculation 0.1g～100g, maleic acid and/or Monosodium maleate 2mg～4.0g；
(2) maleic acid, Monosodium maleate are configured to the solution of 10g/100ml～20g/100ml respectively, standby；
(3) salt of Hirudo, sodium chloride add in 30 DEG C～40 DEG C of water for injection 500ml, stir to after be completely dissolved, addition
Activated carbon, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filters decarburization；
(4) step (3) gained filtrate step (2) configures maleic acid and/or Monosodium maleate solution adjust ph value for 3.0～
7.0, add less than 40 DEG C of water for injection to 1000ml；
(5) by step (4) gained medical filtration to clarification, fill, sterilizing, obtain final product.
2. a kind of preparation method of Hirudo injection agent medicine compositionss according to claim 1 is it is characterised in that institute
State in step (1) maleic acid consumption be 1mg～2.0g, Monosodium maleate consumption be 1mg～2.0g.
3. a kind of Hirudo injection agent medicine compositionss according to claim 1 and 2 preparation method it is characterised in that
Osmotic pressure regulator 9.0g is also included in described step (1).
4. a kind of preparation method of Hirudo injection agent medicine compositionss according to claim 3 is it is characterised in that described
Osmotic pressure regulator is sodium chloride.
5. a kind of preparation method of Hirudo injection agent medicine compositionss according to claim 1 is it is characterised in that described
Hirudo drug injection preparation formulation is injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610968059.9A CN106361693A (en) | 2016-11-06 | 2016-11-06 | Preparation method of leech injection preparation pharmaceutical composition |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610968059.9A CN106361693A (en) | 2016-11-06 | 2016-11-06 | Preparation method of leech injection preparation pharmaceutical composition |
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| CN106361693A true CN106361693A (en) | 2017-02-01 |
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| CN201610968059.9A Withdrawn CN106361693A (en) | 2016-11-06 | 2016-11-06 | Preparation method of leech injection preparation pharmaceutical composition |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108969541A (en) * | 2018-10-23 | 2018-12-11 | 广西中医药大学 | Leech injection preparation process |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101095697A (en) * | 2006-06-28 | 2008-01-02 | 李振国 | Extractive of bdella and/or lumbricus with the molecular weight below 5800 dalton |
-
2016
- 2016-11-06 CN CN201610968059.9A patent/CN106361693A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101095697A (en) * | 2006-06-28 | 2008-01-02 | 李振国 | Extractive of bdella and/or lumbricus with the molecular weight below 5800 dalton |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108969541A (en) * | 2018-10-23 | 2018-12-11 | 广西中医药大学 | Leech injection preparation process |
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Application publication date: 20170201 |
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