CN105963247A - Preparation method of injection medicine for improving stability of quercetin medicine injection preparation - Google Patents
Preparation method of injection medicine for improving stability of quercetin medicine injection preparation Download PDFInfo
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- CN105963247A CN105963247A CN201610310139.5A CN201610310139A CN105963247A CN 105963247 A CN105963247 A CN 105963247A CN 201610310139 A CN201610310139 A CN 201610310139A CN 105963247 A CN105963247 A CN 105963247A
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- injection
- quercetin
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- medicine
- citric acid
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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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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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an injection medicine composition for improving the stability of a quercetin medicine injection preparation, and a preparation method thereof. The injection medicine composition is an injection medicine composition mainly prepared by dissolving salt of quercetin into injection water and adding citric acid and/or sodium citrate as pH regulators to regulate the pH value of medicine liquid. The consumption of the citric acid and/or sodium citrate is 0.1mg to 200.0mg/100ml. The injection medicine composition has the advantages that the pH value of the injection liquid is more stable; the quercetin degradation substances are greatly reduced through being compared with that in the prior art; under the condition of not using other solutizers increasing the clinic application risks, the clarity of the quercetin injection liquid is improved; the problems of small white points, white blocks and solution turbidity of a product of the quercetin injection liquid in the prior art under the condition of long storage time are particularly solved; the visible foreign matter inspection of the product is enabled to conform to the specification of the medicine quality standard; the clinic medication and popularization are convenient.
Description
Technical field
The invention belongs to pharmaceutical technology field, improve Quercetin drug injection preparation stability note in particular it relates to a kind of
Penetrate the preparation method of medicine.
Background technology
Quercetin is dissolved in glacial acetic acid, and alkaline aqueous solution is yellow, is practically insoluble in water, and ethanol solution taste is the most bitter.Can conduct
Medicine, have preferably eliminate the phlegm, antitussive action, and have certain antiasthmatic effect.In addition with reducing blood pressure, strengthening blood capillary
Resistance, minimizing capillary fragility, blood fat reducing, coronary artery dilator, increase the effects such as coronary flow.Chronic for treating
Bronchitis.Coronary heart disease and hyperpietic also there is auxiliary therapeutic action.
Due to Quercetin dissolubility extreme difference in aqueous, therefore it is made into Quercetin hydrochlorate or Quercetin phosphate
To increase its water solublity.Presently commercially available Quercetin injection mainly has the phosphatic low capacity of Quercetin hydrochlorate, Quercetin
Injection, and in Quercetin hydrochlorate, Quercetin phosphate 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 Quercetin injection using above-mentioned pH value regulator to prepare easily is analysed under the conditions of long-term storage and winter low temperature
Going out the precipitate such as tiny white point, white block, solution muddiness, the visible foreign matters check item causing product is defective.Prior art be
Solution adds polyoxyethylene sorbitan monoleate as cosolvent, occur that small particles, white block, solution are muddy etc. and sedimentary ask solving product
Topic.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, cause
Injection clinical practice risk containing polyoxyethylene sorbitan monoleate is higher, makes troubles to clinical application and popularization.
Summary of the invention
The technical problem to be solved is to provide a kind of injection improving Quercetin drug injection preparation stability
The preparation method of pharmaceutical composition.This medicinal composition for injections employing citric acid, sodium citrate are as pH adjusting agent, and lead to
When crossing creative work discovery employing citric acid, sodium citrate as pH adjusting agent, medicinal liquid pH value is more stable, and Quercetin is degraded
Material relatively prior art is substantially reduced, and in the case of avoiding using other to increase the cosolvent of clinical practice risk, makes us full
Meaning ground solves Quercetin injection, and under the conditions of long-term storage and winter low temperature, easily the tiny white point of precipitation, white block, solution are muddy
Turbid problem.
The present invention solves the problems referred to above and be the technical scheme is that a kind of raising Quercetin drug injection preparation stability
Medicinal composition for injections, be mainly dissolved in water for injection by the salt of Quercetin, add osmotic pressure regulator, and add citric acid
And/or the medicinal composition for injections that sodium citrate is made as pH adjusting agent regulation medicinal liquid pH value, described citric acid and/or Chinese holly
The consumption of rafter acid sodium is 0.1mg～200.0mg/100ml.
Described osmotic pressure regulator is any one or a few in glucose, sodium chloride, xylitol, mannitol, 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 Quercetin includes Quercetin hydrochlorate, Quercetin phosphate.
The concentration of the salt of described Quercetin is calculated as 10mg～10g/100ml with Quercetin.
Described medicinal liquid pH value is 3.0～6.0.
Described Quercetin drug injection preparation formulation is injection.
The preparation method of the medicinal composition for injections of above-mentioned raising Quercetin drug injection preparation stability, including following
Step:
(1) salt of Quercetin is weighed with Quercetin amount of calculation 0.1g～100g, citric acid and/or sodium citrate 2mg～4.0g；
(2) citric acid, sodium citrate are configured to the solution of 10g/100ml～20g/100ml respectively, standby；
(3) salt of Quercetin, sodium chloride add in the water for injection 500ml of 30 DEG C～40 DEG C, stir to after being completely dissolved, add
The activated carbon entered, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filters decarburization；
(4) step (3) gained filtrate step (2) configures citric acid and/or liquor sodii citratis regulation pH value be 3.0～
7.0, 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) citric acid consumption be 1mg～2.0g, sodium citrate consumption be 1mg～2.0g.
Described step also includes osmotic pressure regulator 9.0g in (1).
Described osmotic pressure regulator is sodium chloride.
In such scheme, what addition citric acid and/or sodium citrate referred to addition can be in citric acid, sodium citrate
Any one, or citric acid, sodium citrate are with arbitrary proportion proportioning；In step (2), the citric acid of addition, sodium citrate
In one, then make a kind of solution, as included citric acid, sodium citrate two kinds, be configured to solution for standby the most respectively；Quercetin
Salt, 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, in Quercetin drug injection system
In agent, when using citric acid, sodium citrate as pH adjusting agent, medicinal liquid pH value is more stable, and Quercetin degradation material is more existing
Technology is substantially reduced, and in the case of avoiding using other to increase the cosolvent of clinical practice risk, is satisfactorily addressed
Quercetin injection uses 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 keeping injection that Quercetin injection can be stable in storage process meets medicine matter
The regulation of amount standard, it is simple to clinical application and popularization.
The present invention passes through creative work, to muddy former of the tiny white point separated out in Quercetin injection, white block, solution
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 the kind of acid used by the pH value of solution and pH adjusting agent, alkali.Therefore use sodium citrate is as pH adjusting agent,
And use citric acid as pH value counter regulation agent, in the case of avoiding using other to increase the cosolvent of clinical practice risks,
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 medicinal composition for injections improving Quercetin drug injection preparation stability, including following step
Rapid: (1) weighting raw materials is with Quercetin amount of calculation 0.1g～100g, sodium chloride 9.0g, citric acid 1mg～2.0g, sodium citrate
1mg～2.0g；(2) citric acid, sodium citrate are configured to the solution of 10%～20% respectively, standby.(3) less than 40 DEG C are added
In water for injection 500ml, stir to after being completely dissolved, add 0.02%(g/ml) activated carbon, stir 15 minutes, filtration decarburization.
(4) filtrate citric acid or liquor sodii citratis regulation pH value are 3.0～7.0, add the water for injection of less than 40 DEG C extremely
1000ml；(5) medical filtration is to clarification, fill, sterilizing, to obtain final product.
Composition and the content thereof of the concrete each component of the present embodiment are as follows:
Hydrochloric acid Quercetin 0.8g
Sodium chloride 9.0g
Citric acid 1.0g
Sodium citrate 2.0g
Citric acid, sodium citrate are configured to the solution of 10%～20% respectively, standby.Hydrochloric acid Quercetin, sodium chloride add 40 DEG C with
Under water for injection 500ml in, stir to after being completely dissolved, add 0.02% activated carbon (i.e. activated carbon dosage is 0.02g/
100ml), stir 15 minutes, filter decarburization.Filtrate citric acid or liquor sodii citratis regulation pH value are 3.8～4.2, add
The water for injection of less than 40 DEG C is to 1000ml.Medical filtration, to clarification, fill, sterilizing, to obtain final product.
Embodiment 2
Or, the medicinal composition for injections of above-mentioned raising Quercetin drug injection preparation stability is prepared according to the following steps:
(1) weighting raw materials is with Quercetin amount of calculation 0.1g～100g, citric acid 1mg～2.0g, sodium citrate 1mg～2.0g；
(2) citric acid, sodium citrate are configured to the solution of 10%～20% respectively, standby.(3) water for injection of less than 40 DEG C is added
In 500ml, stir to after being completely dissolved, add 0.02%(g/ml) activated carbon, stir 15 minutes, filtration decarburization.(4) filtrate
Regulating pH value with citric acid or liquor sodii citratis is 3.0～7.0, adds the water for injection of less than 40 DEG C to 1000ml；(5)
Medical filtration, to clarification, fill, sterilizing, to obtain final product.
Composition and the content thereof of the concrete each component of the present embodiment are as follows:
Hydrochloric acid Quercetin 20g
Citric acid 1.0g
Sodium citrate 2.0g
Citric acid, sodium citrate are configured to the solution of 10%～20% respectively, standby.Hydrochloric acid Quercetin adds the injection of less than 40 DEG C
With in water 500ml, stir to after being completely dissolved, add the activated carbon (i.e. activated carbon dosage is 0.02g/100ml) of 0.02%, stir
Mix 15 minutes, filter decarburization.Filtrate citric acid or liquor sodii citratis regulation pH value are 3.8～4.2, add less than 40 DEG C
Water for injection is to 1000ml.Medical filtration, to clarification, fill, sterilizing, to obtain final product.
Embodiment 3
Quercetin sodium chloride injection stability comparative test
The visible foreign matters detection utilizing Quercetin sodium chloride injection obtained by the present invention meets the regulation of drug standard, and
Stability of solution is fine, in the case of avoiding using other to increase the cosolvent of clinical practice risk, solves Quercetin chlorine
Change sodium injection and the problems such as small particles, white block, solution are muddy easily occur in storage process.Utilize the Cortex querci dentatae obtained by the present invention
Element sodium chloride injection is according to the phase of two annex Ⅺ Ⅹ C pharmaceutical preparation stability test guidelines of China's coastal port
Close requirement, investigated respectively 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 placement 20
It medicine stability, result constant product quality at the conditions of the experiments described above, every Testing index all meets this product quality standard
Regulation.
The pharmacological results shows: utilize stable Quercetin sodium chloride injection obtained by the present invention without hemolytic,
Without 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 Quercetin sodium chloride injection
3 40 DEG C of study on the stability results of table
Table 4 0～5 DEG C of low temperature visible foreign matters investigate result
According to the above results, the Quercetin drug injection preparation of the present invention can improve the clarity of Quercetin injection,
Particularly in the case of Quercetin injection period of storage is longer, it is possible to the stable visible foreign matters detection keeping injection meets
The regulation of drug standard, solves Quercetin medicine and uses existing technical products to occur little in the case of period of storage is longer
The problem that white point, white block, solution are muddy, it is ensured that the visible foreign matters inspection of product meets the regulation of drug standard, just
In clinical application and popularization.
As it has been described above, just can preferably realize the present invention.
Claims (4)
1. the preparation method improving Quercetin drug injection preparation stability injection medicine, it is characterised in that include following
Step:
(1) salt of Quercetin is weighed with Quercetin amount of calculation 0.1g～100g, citric acid and/or sodium citrate 2mg～4.0g；
(2) citric acid, sodium citrate are configured to the solution of 10g/100ml～20g/100ml respectively, standby；
(3) salt of Quercetin, sodium chloride add in the water for injection 500ml of 30 DEG C～40 DEG C, stir to after being completely dissolved, add
The activated carbon entered, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filters decarburization；
(4) step (3) gained filtrate step (2) configures citric acid and/or liquor sodii citratis regulation pH value be 3.0～
7.0, add the water for injection of less than 40 DEG C to 1000ml；
(5) by step (4) gained medical filtration to clarification, fill, sterilizing, to obtain final product.
A kind of preparation method improving Quercetin drug injection preparation stability injection medicine the most according to claim 1,
It is characterized in that, in described step (1) citric acid consumption be 1mg～2.0g, sodium citrate consumption be 1mg～2.0g.
A kind of preparation method improving Quercetin drug injection preparation stability injection medicine the most according to claim 1,
It is characterized in that, described step also includes osmotic pressure regulator 9.0g in (1).
A kind of preparation method improving Quercetin drug injection preparation stability injection medicine the most according to claim 4,
It is characterized in that, described osmotic pressure regulator is sodium chloride.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610310139.5A CN105963247A (en) | 2016-05-12 | 2016-05-12 | Preparation method of injection medicine for improving stability of quercetin medicine injection preparation |
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| CN201610310139.5A CN105963247A (en) | 2016-05-12 | 2016-05-12 | Preparation method of injection medicine for improving stability of quercetin medicine injection preparation |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344636A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Preparation method of Chinese thorowax root injection preparation pharmaceutical composition |
| 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 |
| CN106511424A (en) * | 2016-11-06 | 2017-03-22 | 成都先先先生物科技有限公司 | Preparation method of herba artemisiae annuae injection preparation medicinal composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2016
- 2016-05-12 CN CN201610310139.5A patent/CN105963247A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344636A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Preparation method of Chinese thorowax root injection preparation pharmaceutical composition |
| 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 |
| CN106511424A (en) * | 2016-11-06 | 2017-03-22 | 成都先先先生物科技有限公司 | Preparation method of herba artemisiae annuae injection preparation medicinal composition |
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Application publication date: 20160928 |