CN105902487A - Injection pharmaceutical composition capable of improving stability of quercetin medication injection preparation - Google Patents
Injection pharmaceutical composition capable of improving stability of quercetin medication injection preparation Download PDFInfo
- Publication number
- CN105902487A CN105902487A CN201610310123.4A CN201610310123A CN105902487A CN 105902487 A CN105902487 A CN 105902487A CN 201610310123 A CN201610310123 A CN 201610310123A CN 105902487 A CN105902487 A CN 105902487A
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- CN
- China
- Prior art keywords
- quercetin
- injection
- pharmaceutical composition
- injection preparation
- citric acid
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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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
-
- 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
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
Abstract
The invention discloses an injection pharmaceutical composition capable of improving stability of a quercetin medication injection preparation and a preparing method of the injection pharmaceutical composition. The injection pharmaceutical composition is mainly prepared by dissolving quercetin salt in injection water and adding citric acid and/or sodium citrate as a pH conditioning agent to adjust a pH value of pharmaceutical liquid, and the using amount of the citric acid and/or sodium citrate is 0.1mg-200.0mg/100ml. The injection pharmaceutical composition can enable a pH value of the injection preparation to be more stable, quercetin degradation substances are greatly reduced compared with the prior art, and the clarity of the quercetin injection preparation is improved in a situation that other cosolvent which can increase clinical application risk is prevented from being used. Especially, the problems that quercetin injection preparation in the prior art is prone to generating small white particles and white blocks and solution turbidity after being stored for a long time are solved, visible foreign matter inspection of the product can meet a regulation of a medicine quality standard, and the injection pharmaceutical composition is convenient to be applied to clinical medication and popularize.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to a kind of medicinal composition for injections improving Quercetin drug injection preparation stability.
Background technology
Quercetin is the alkaloid extracted from Chinese medicine Herba Gelsemii Elegantis, have preferably eliminate the phlegm, antitussive action, and have certain antiasthmatic effect.
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 injection with small volume of Quercetin hydrochlorate, Quercetin, and the high-capacity injection that addition glucose or sodium chloride are made in Quercetin hydrochlorate, Quercetin phosphate solution as osmotic pressure regulator.But when preparing above-mentioned injection, must be adjusted to the pH value of medicinal liquid be suitable for the certain limit that human injection is administered, the pH value regulator that document report uses at present is sodium hydroxide solution or uses hydrochloric acid solution, phosphoric acid solution, but the Quercetin injection using above-mentioned pH value regulator to prepare easily separates out the precipitate such as tiny white point, white block, solution muddiness under the conditions of storage for a long time and winter low temperature, and the visible foreign matters check item causing product is defective.Prior art is to add polyoxyethylene sorbitan monoleate in the solution as cosolvent, the sedimentary problems such as small particles, white block, solution are muddy occurs solving product.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 the injection clinical practice risk containing polyoxyethylene sorbitan monoleate higher, make troubles to clinical application and popularization.
Summary of the invention
The technical problem to be solved is to provide a kind of medicinal composition for injections improving Quercetin drug injection preparation stability.This medicinal composition for injections uses citric acid, sodium citrate as pH adjusting agent, and when finding to use citric acid, sodium citrate as pH adjusting agent by creative work, medicinal liquid pH value is more stable, Quercetin degradation material relatively prior art is substantially reduced, in the case of avoiding using other to increase the cosolvent of clinical practice risk, Quercetin injection is satisfactorily addressed under the conditions of storage for a long time and winter low temperature, has easily separated out tiny white point, white block, the problem of solution muddiness.
The present invention solves the problems referred to above and be the technical scheme is that a kind of medicinal composition for injections improving Quercetin drug injection preparation stability, mainly it is dissolved in water for injection by the salt of Quercetin, add osmotic pressure regulator, and adding the medicinal composition for injections that citric acid and/or sodium citrate are made as pH adjusting agent regulation medicinal liquid pH value, the consumption of described citric acid and/or sodium citrate 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 are 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, comprises the steps:
(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, and the activated carbon of addition, described activated carbon dosage is 0.02g/100ml, stir 15 minutes, filtration decarburization；
(4) step (3) gained filtrate step (2) configures citric acid and/or liquor sodii citratis regulation pH value are 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 any one in citric acid, sodium citrate, or citric acid, sodium citrate are with arbitrary proportion proportioning；In step (2), the one in the citric acid of addition, sodium citrate, then make a kind of solution, as included citric acid, sodium citrate two kinds, be configured to solution for standby the most respectively；The salt of Quercetin, 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 preparation, use citric acid, when sodium citrate is as pH adjusting agent, medicinal liquid pH value is more stable, Quercetin degradation material relatively prior art is substantially reduced, in the case of avoiding using other to increase the cosolvent of clinical practice risk, Quercetin injection has been satisfactorily addressed uses prior art products easily to separate out tiny white point in storage process, white block, the problem that solution is muddy, can ensure that the visible foreign matters detection keeping injection that Quercetin injection can be stable in storage process meets the regulation of drug standard, it is easy to clinical application and popularization.
The present invention passes through creative work, the tiny white point separated out in Quercetin injection, white block, the reason of solution muddiness are analyzed and study, determine that deposit is mainly raw material free alkali crystallize and a small amount of catabolite, occur that above-mentioned reason may be relevant with the kind of acid used by the pH value of solution and pH adjusting agent, alkali.Therefore use sodium citrate 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 risk, 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, comprises the steps: that (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) add in the water for injection 500ml of less than 40 DEG C, 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 to 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 in the water for injection 500ml of less than 40 DEG C, stir to after being completely dissolved, add the activated carbon (i.e. activated carbon dosage is 0.02g/100ml) of 0.02%, stir 15 minutes, filtration 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 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) add in the water for injection 500ml of less than 40 DEG C, 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 to 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
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 in the water for injection 500ml of less than 40 DEG C, stirs to after being completely dissolved, adds the activated carbon (i.e. activated carbon dosage is 0.02g/100ml) of 0.02%, stir 15 minutes, filtration 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 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, solve Quercetin sodium chloride injection and the problems such as small particles, white block, solution are muddy easily occur in storage process.Utilize the Quercetin sodium chloride injection obtained by the present invention according to the related request of two annex Ⅺ Ⅹ C pharmaceutical preparation stability test guidelines of China's coastal port, investigate 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 20 days medicine stability of placement, result constant product quality at the conditions of the experiments described above, every Testing index all meets the regulation of this product quality standard.
The pharmacological results shows: utilizes the stable Quercetin sodium chloride injection obtained by the present invention without hemolytic, without anaphylaxis, nonirritant, meets the requirement of drug administration by injection.
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, the visible foreign matters keeping injection that can be stable detects the regulation meeting drug standard, solving Quercetin medicine uses existing technical products to occur the problem that small particles, white block, solution are muddy in the case of period of storage is longer, can ensure that the visible foreign matters inspection of product meets the regulation of drug standard, it is simple to clinical application and popularization.
As it has been described above, just can preferably realize the present invention.
Claims (6)
1. the medicinal composition for injections improving Quercetin drug injection preparation stability, it is characterized in that, mainly it is dissolved in water for injection by the salt of Quercetin, adding the medicinal composition for injections that citric acid and/or sodium citrate are made as pH adjusting agent regulation medicinal liquid pH value, the consumption of described citric acid and/or sodium citrate is 0.1mg～200.0mg/100ml.
A kind of medicinal composition for injections improving Quercetin drug injection preparation stability the most according to claim 1, it is characterized in that, also include that osmotic pressure regulator, described osmotic pressure regulator are any one or a few in glucose, sodium chloride, xylitol, mannitol, fructose.
A kind of medicinal composition for injections improving Quercetin drug injection preparation stability the most according to claim 1, it is characterised in that the salt of described Quercetin includes Quercetin hydrochlorate, Quercetin phosphate.
4. according to a kind of medicinal composition for injections improving Quercetin drug injection preparation stability described in claim 1 or 3, it is characterised in that the concentration of the salt of described Quercetin is calculated as 10mg～10g/100ml with Quercetin.
A kind of medicinal composition for injections improving Quercetin drug injection preparation stability the most according to claim 1, it is characterised in that described medicinal liquid pH value is 3.0～6.0.
A kind of medicinal composition for injections improving Quercetin drug injection preparation stability the most according to claim 1, it is characterised in that described Quercetin drug injection preparation formulation is injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610310123.4A CN105902487A (en) | 2016-05-12 | 2016-05-12 | Injection pharmaceutical composition capable of improving stability of quercetin medication injection preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610310123.4A CN105902487A (en) | 2016-05-12 | 2016-05-12 | Injection pharmaceutical composition capable of improving stability of quercetin medication injection preparation |
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| CN105902487A true CN105902487A (en) | 2016-08-31 |
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| CN201610310123.4A Withdrawn CN105902487A (en) | 2016-05-12 | 2016-05-12 | Injection pharmaceutical composition capable of improving stability of quercetin medication injection preparation |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1383381A (en) * | 2000-08-14 | 2002-12-04 | 韩国韩医学研究院 | Therpauetic agent of osteoporisis comprising active ingredient of quercetin derivatives |
| 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 CN201610310123.4A patent/CN105902487A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1383381A (en) * | 2000-08-14 | 2002-12-04 | 韩国韩医学研究院 | Therpauetic agent of osteoporisis comprising active ingredient of quercetin derivatives |
| 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 |
Non-Patent Citations (1)
| Title |
|---|
| 殷伟平等: "穴位注射槲皮素镇痛作用途径的初步分析", 《苏州医学院学报》 * |
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Application publication date: 20160831 |