CN106344501A - Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation - Google Patents
Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation Download PDFInfo
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- CN106344501A CN106344501A CN201610968023.0A CN201610968023A CN106344501A CN 106344501 A CN106344501 A CN 106344501A CN 201610968023 A CN201610968023 A CN 201610968023A CN 106344501 A CN106344501 A CN 106344501A
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- Prior art keywords
- berberine
- injection
- acetic acid
- glacial acetic
- pharmaceutical composition
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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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a pharmaceutical composition for injection capable of improving the stability of a berberine drug injection preparation. The pharmaceutical composition for injection is mainly prepared by the following steps: dissolving salts of berberine in water for injection, and adding glacial acetic acid and/or sodium glacial acetic acid as a pH regulator to regulate the pH value of the medicinal liquor, thereby obtaining the pharmaceutical composition for injection, wherein the dosage of the glacial acetic acid and/or sodium glacial acetic acid is 0.1-200.0mg/100ml. According to the invention, the pH value of the injection can be stable, berberine degradation materials are greatly reduced compared with that in the prior art, the clarity of the berberine injection is improved under the condition that use of other cosolvents capable of increasing the clinical application risk is avoided, particularly the problems that small white dots, white blocks and turbid solutions occur in the berberine injection by adopting existing technology products under the condition that the storage time is long are solved, inspection of visible foreign matters can be guaranteed to meet provisions in the drug standard, and the pharmaceutical composition is convenient for clinical medication and popularization.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to a kind of raising berberine drug injection preparation stability
Medicinal composition for injections.
Background technology
Berberine is the alkaloid extracting from chuanxiong, and chemical constitution is tetramethylpyazine, be a kind of new calcium from
Sub- antagonist, have blood circulation promoting and blood stasis dispelling, anti-platelet aggregation, excited medullary respiratory center and vasomotor center, expansion of blood vessels and
Bronchial smooth muscle, improve multiple effect such as microcirculation, be clinically used for for obliterated cerebral vascular disease such as incomplete brain blood supply, brain
Thrombosiss, cerebral embolism and other ischemic angiopathys such as coronary heart disease, vasculitiss etc..The injection of berberine has been Chinese medicine
Treatment modern hardly possible disease makes very big contribution.
Due to berberine dissolubility extreme difference in aqueous, therefore it is made into berberine hydrochloride or berberine phosphate
To increase its water solublity.Presently commercially available berberine injection mainly has the phosphatic low capacity of berberine hydrochloride, berberine
Injection, and add glucose or sodium chloride to adjust as osmotic pressure in berberine hydrochloride, berberine phosphate solution
The high-capacity injection that agent is made.But when preparing above-mentioned injection it is necessary to the ph value of medicinal liquid is adjusted to suitable human injection
The certain limit of administration, the ph value regulator that current document report uses is sodium hydroxide solution or uses hydrochloric acid solution, phosphorus
Acid solution, but easily analysed under the conditions of long-term storage and winter low temperature using the berberine injection of above-mentioned ph value regulator preparation
Go out the precipitate such as tiny white point, white block, solution muddiness, cause the visible foreign matters check item of product unqualified.Prior art be
Add polyoxyethylene sorbitan monoleate in solution as cosolvent, occur that small particles, white block, solution muddiness etc. are sedimentary to ask to solve product
Topic.But polyoxyethylene sorbitan monoleate is due to having the effect of haemolysis and blood pressure lowering, and easily become sour in storage and autoclaving process, lead to
Injection clinical practice risk containing polyoxyethylene sorbitan monoleate is higher, makes troubles to clinical application and popularization.
Content of the invention
The technical problem to be solved is to provide a kind of injection improving berberine drug injection preparation stability
Pharmaceutical composition.
This medicinal composition for injections adopts glacial acetic acid, glacial acetic acid sodium is as ph regulator, and is sent out by creative work
When now adopting glacial acetic acid, glacial acetic acid sodium as ph regulator, medicinal liquid ph value is more stable, and berberine degradation material is compared with prior art
Substantially reduce, in the case of avoiding increasing the cosolvent of clinical practice risk using other, Rhizoma Coptidis have been satisfactorily addressed
Plain injection 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 and be the technical scheme is that a kind of raising berberine drug injection preparation stability
Medicinal composition for injections, mainly water for injection is dissolved in by the salt of berberine, adds osmotic pressure regulator, and add glacial acetic acid
And/or medicinal composition for injections, described glacial acetic acid and/or the ice that glacial acetic acid sodium is made as ph regulator regulating liquid medicine ph value
The consumption of Sodium Acetate Trihydrate 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 berberine includes berberine hydrochloride, berberine phosphate.
The concentration of the salt of described berberine is calculated as 10mg～10g/100ml with berberine.
Described medicinal liquid ph value is 3.0～6.0.
Described berberine drug injection preparation formulation is injection.
The preparation method of the medicinal composition for injections of above-mentioned raising berberine drug injection preparation stability, including following
Step:
(1) weigh the salt of berberine with berberine amount of calculation 0.1g～100g, glacial acetic acid and/or glacial acetic acid sodium 2mg～
4.0g；
(2) glacial acetic acid, glacial acetic acid sodium are configured to the solution of 10g/100ml～20g/100ml respectively, standby；
(3) salt of berberine, sodium chloride add in 30 DEG C～40 DEG C of water for injection 500ml, stir to after be completely dissolved,
The activated carbon adding, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filters decarburization；
(4) glacial acetic acid that step (3) gained filtrate step (2) configures and/or glacial acetic acid sodium 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) glacial acetic acid consumption be 1mg～2.0g, glacial acetic acid sodium 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 glacial acetic acid and/or glacial acetic acid sodium refers to add can be glacial acetic acid, in glacial acetic acid sodium
Any one, or glacial acetic acid, glacial acetic acid sodium are with arbitrary proportion proportioning；In step (2), the glacial acetic acid of addition, glacial acetic acid sodium
One of, then make a kind of solution, such as include glacial acetic acid, two kinds of glacial acetic acid sodium, be then configured to solution for standby respectively；Berberine
Salt, the consumption of osmotic pressure regulator can adopt the consumption of prior art, according to the adjustment of the consumption of prior art.
In sum, the invention has the beneficial effects as follows: the present invention pass through experimental studies have found that, in berberine drug injection system
In agent, during using glacial acetic acid, glacial acetic acid sodium as ph regulator, medicinal liquid ph value is more stable, and berberine degradation material is more existing
Technology substantially reduces, and in the case of avoiding increasing the cosolvent of clinical practice risk using other, is satisfactorily addressed
Berberine injection adopts prior art products easily to separate out tiny white point, white block, the problem of solution muddiness in storage process,
Can ensure that the visible foreign matters detection of the holding injection that berberine injection can be stable in storage process meets medicine matter
The regulation of amount standard, is easy to clinical application and popularization.
The present invention passes through creative work, and muddy to the tiny white point separating out in berberine injection, white block, solution is former
Because being analyzed and studying, determine that deposit is mainly raw material free alkali crystallize and a small amount of catabolite, above-mentioned reason occurs
May be relevant with species sour, alkali used by the ph value of solution and ph regulator.Glacial acetic acid sodium is therefore used as ph regulator,
And glacial acetic acid is used as ph value counter regulation agent, in the case of avoiding increasing the cosolvent of clinical practice risk using other,
To solve the problems, such as this product, under the conditions of long-term storage and winter low temperature, easily the tiny white point of precipitation, white block, solution are muddy.
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 medicinal composition for injections improving berberine drug injection preparation stability, including following
Step: (1) weighs crude drug with berberine amount of calculation 0.1g～100g, sodium chloride 9.0g, glacial acetic acid 1mg～2.0g, glacial acetic acid
Sodium 1mg～2.0g；(2) glacial acetic acid, glacial acetic acid sodium are configured to 10%～20% solution respectively, standby.(3) less than 40 DEG C are added
Water for injection 500ml in, stir to after be completely dissolved, add the activated carbon of 0.02% (g/ml), stir 15 minutes, filter de-
Carbon.(4) filtrate glacial acetic acid or glacial acetic acid sodium solution regulation ph value are 3.0～7.0, add less than 40 DEG C of water for injection extremely
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:
Glacial acetic acid, glacial acetic acid sodium are configured to 10%～20% solution respectively, standby.Berberine hydrochloride, sodium chloride add
In less than 40 DEG C of water for injection 500ml, 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 glacial acetic acid or glacial acetic acid sodium 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, the medicinal composition for injections of above-mentioned raising berberine drug injection preparation stability is made in the steps below
Standby:
(1) weigh crude drug with berberine amount of calculation 0.1g～100g, glacial acetic acid 1mg～2.0g, glacial acetic acid sodium 1mg～
2.0g；(2) glacial acetic acid, glacial acetic acid sodium 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 glacial acetic acid or glacial acetic acid sodium 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:
Berberine hydrochloride 20g
Glacial acetic acid 1.0g
Glacial acetic acid sodium 2.0g
Glacial acetic acid, glacial acetic acid sodium are configured to 10%～20% solution respectively, standby.Berberine hydrochloride adds less than 40 DEG C
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 glacial acetic acid or glacial acetic acid sodium 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
Berberine sodium chloride injection stability comparative test
Visible foreign matters detection using berberine sodium chloride injection obtained by the present invention meets the rule of drug standard
Fixed, and stability of solution is very well, in the case of avoiding increasing the cosolvent of clinical practice risk using other, solves Rhizoma Coptidis
Plain sodium chloride injection easily the problems such as small particles, white block, solution muddiness in storage process.Using obtained by the present invention
Berberine sodium chloride injection is according to two annex c pharmaceutical preparation stability test guidelines of China's coastal port
Related request, investigated respectively 25 DEG C place place within 24 months, 40 DEG C place 10 days within 6 months, 60 DEG C, 0～5 DEG C of low temperature puts
Put 20 days medicine stabilities, product quality is stable at the conditions of the experiments described above for result, and every Testing index all meets this quality
The regulation of standard.
The pharmacological results show: using the stable berberine sodium chloride injection obtained by the present invention no hemolytic,
No anaphylaxis, nonirritant, meets the requirement of drug administration by injection.
1 25 DEG C of study on the stability results of table
Table 60 DEG C of study on the stability results of 2 berberine hydrochloride 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 berberine drug injection preparation of the present invention can improve the clear and bright of berberine injection
Degree, particularly in the case that berberine injection period of storage is longer, the visible foreign matters detection of holding injection that can be stable
Meet the regulation of drug standard, solve berberine medicine and gone out in the case that period of storage is longer using existing technical products
The muddy problem of existing small particles, white block, solution is it is ensured that the visible foreign matters inspection of product meets the rule of drug standard
Fixed, it is easy to clinical application and popularization.
As described above, just can preferably realize the present invention.
Claims (6)
1. a kind of medicinal composition for injections improving berberine drug injection preparation stability it is characterised in that main by Huang
The salt of Lian Su is dissolved in water for injection, adds the note that glacial acetic acid and/or glacial acetic acid sodium are made as ph regulator regulating liquid medicine ph value
Penetrate pharmaceutical composition, the consumption of described glacial acetic acid and/or glacial acetic acid sodium is 0.1mg～200.0mg/100ml.
2. a kind of medicinal composition for injections improving berberine drug injection preparation stability according to claim 1,
It is characterized in that, also include osmotic pressure regulator, described osmotic pressure regulator be glucose, sodium chloride, xylitol, Mannitol,
Any one or a few in Fructose.
3. a kind of medicinal composition for injections improving berberine drug injection preparation stability according to claim 1,
It is characterized in that, the salt of described berberine includes berberine hydrochloride, berberine phosphate.
4. the injectable drug combination of a kind of raising berberine drug injection preparation stability according to claim 1 or 3
Thing is it is characterised in that the concentration of the salt of described berberine is calculated as 10mg～10g/100ml with berberine.
5. a kind of medicinal composition for injections improving berberine drug injection preparation stability according to claim 1,
It is characterized in that, described medicinal liquid ph value is 3.0～6.0.
6. a kind of medicinal composition for injections improving berberine drug injection preparation stability according to claim 1,
It is characterized in that, described berberine drug injection preparation formulation is injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610968023.0A CN106344501A (en) | 2016-11-06 | 2016-11-06 | Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610968023.0A CN106344501A (en) | 2016-11-06 | 2016-11-06 | Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation |
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| Publication Number | Publication Date |
|---|---|
| CN106344501A true CN106344501A (en) | 2017-01-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610968023.0A Withdrawn CN106344501A (en) | 2016-11-06 | 2016-11-06 | Pharmaceutical composition for injection capable of improving stability of berberine drug injection preparation |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1663567A (en) * | 2004-03-05 | 2005-09-07 | 罗靖 | Compound methionine vitamin B1Freeze-dried powder injection preparation and preparation method thereof |
| CN101822670A (en) * | 2010-03-17 | 2010-09-08 | 中国人民解放军第二军医大学 | Application of berberine in preparing medicament for preventing and treating rheumatoid arthritis |
| CN105106110A (en) * | 2015-09-23 | 2015-12-02 | 成都艾比科生物科技有限公司 | Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition |
-
2016
- 2016-11-06 CN CN201610968023.0A patent/CN106344501A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1663567A (en) * | 2004-03-05 | 2005-09-07 | 罗靖 | Compound methionine vitamin B1Freeze-dried powder injection preparation and preparation method thereof |
| CN101822670A (en) * | 2010-03-17 | 2010-09-08 | 中国人民解放军第二军医大学 | Application of berberine in preparing medicament for preventing and treating rheumatoid arthritis |
| CN105106110A (en) * | 2015-09-23 | 2015-12-02 | 成都艾比科生物科技有限公司 | Injectable medicine composition capable of improving stability of puerarin medicine injection preparation and preparation method of injectable medicine composition |
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Application publication date: 20170125 |