CN105999278A - Injecting medicine composition for improving stability of ginsenoside medicine injection - Google Patents
Injecting medicine composition for improving stability of ginsenoside medicine injection Download PDFInfo
- Publication number
- CN105999278A CN105999278A CN201610353138.9A CN201610353138A CN105999278A CN 105999278 A CN105999278 A CN 105999278A CN 201610353138 A CN201610353138 A CN 201610353138A CN 105999278 A CN105999278 A CN 105999278A
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- CN
- China
- Prior art keywords
- ginsenoside
- injection
- citric acid
- sodium citrate
- preparation
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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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- 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
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- 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
-
- 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
Abstract
The invention discloses an injecting medicine composition for improving the stability of a ginsenoside medicine injection and a preparation method thereof. The preparation method mainly comprises the following steps: dissolving salt of ginsenoside in injecting water; adding citric acid and/or sodium citrate to serve as a pH regulator, and regulating the pH value of the medicinal liquid, wherein the dosage of the citric acid and/or sodium citrate is 0.1-200.0mg/100ml. By adopting the preparation method, the pH value of the injection can be stable, the ginsenoside degraded substances are greatly reduced in comparison with that in the prior art, the clarity of ginsenoside injection is improved under a condition that other cosolvent capable of increasing clinical application risks is prevented from being used, and the problems that the ginsenoside injection has small spots, white blocks and turbid solution by adopting the prior art under a condition of long storage period can be especially solved, obviously foreign matter inspection of the injection accords with the specification of medicine quality standard, and clinical medication and popularization can be benefited.
Description
Technical field
The invention belongs to pharmaceutical technology field, improve ginsenoside's drug injection preparation in particular it relates to a kind of
The medicinal composition for injections of stability.
Background technology
Ginsenoside (Ginsenoside) is a kind of steroid compound, triterpene saponin.It is primarily present in people
Ginseng belongs in medical material.Ginsenoside is considered to be the active component in Radix Ginseng, thus becomes the target of research.Cause
Multiple metabolic pathway is have impact on for ginsenoside, so its usefulness is also complicated, and various Radix Ginseng soap
The monomer component of glycosides is difficult to separate.Be grown in archipelago, the South Pacific Ocean wild plants to sky fruit is the most this
Thing contains ginsenoside's composition equally, has the most a wide range of medicinal efficacy.
Due to ginsenoside's dissolubility extreme difference in aqueous, therefore it is made into ginsenoside's hydrochlorate or people
Ginseng saponin phosphate is to increase its water solublity.Presently commercially available ginsenoside's injection mainly has ginsenoside's salt
Hydrochlorate, the phosphatic injection with small volume of ginsenoside, and at ginsenoside's hydrochlorate, ginsenoside's phosphorus
The high-capacity injection that in acid salt solution, addition glucose or sodium chloride are made as osmotic pressure regulator.But
When preparing above-mentioned injection, it is necessary to 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 molten
Liquid, but use ginsenoside's injection prepared by above-mentioned pH value regulator in long-term storage and winter low temperature condition
The precipitate such as the tiny white point of lower easily precipitation, white block, solution are muddy, cause the visible foreign matters check item of product
Defective.Prior art is that addition polyoxyethylene sorbitan monoleate is as cosolvent in the solution, little to solve product appearance
The sedimentary problems such as white point, white block, solution are muddy.But polyoxyethylene sorbitan monoleate is owing to having haemolysis and blood pressure lowering
Effect, and easily become sour in storage and autoclaving process, cause the injection containing polyoxyethylene sorbitan monoleate to face
Bed application risk 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 raising ginsenoside's drug injection preparation stability
Medicinal composition for injections.This medicinal composition for injections uses citric acid, sodium citrate as pH regulator
Agent, and when finding to use citric acid, sodium citrate as pH adjusting agent by creative work, medicinal liquid pH
Being worth more stable, ginsenoside's degradation material relatively prior art is substantially reduced, and uses other increases to face avoiding
In the case of the cosolvent of bed application risk, ginsenoside injection is satisfactorily addressed in long-term storage
With the tiny white point of easy precipitation, white block, the problem of solution muddiness under the conditions of winter low temperature.
The present invention solves the problems referred to above and be the technical scheme is that a kind of raising ginsenoside's drug injection system
The medicinal composition for injections of agent stability, is mainly dissolved in water for injection by the salt of ginsenoside, adds infiltration
Pressure regulator, and add the note that citric acid and/or sodium citrate are made as pH adjusting agent regulation medicinal liquid pH value
Penetrating pharmaceutical composition, the consumption of described citric acid and/or sodium citrate is 0.1mg～200.0mg/100ml.
Described osmotic pressure regulator be in glucose, sodium chloride, xylitol, mannitol, fructose any one or
Several.The consumption of osmotic pressure regulator is prior art, and sodium chloride consumption is 0.9g/100ml；Glucose, wood
Sugar alcohol, mannitol, fructose consumption are 5g/100ml～10g/100ml.
The salt of described ginsenoside includes ginsenoside's hydrochlorate, ginsenoside's phosphate.
The concentration of the salt of described ginsenoside is calculated as 10mg～10g/100ml with ginsenoside.
Described medicinal liquid pH value is 3.0～6.0.
Described ginsenoside's drug injection preparation formulation is injection.
The preparation method of the medicinal composition for injections of above-mentioned raising ginsenoside's drug injection preparation stability,
Comprise the steps:
(1) salt of ginsenoside is weighed with ginsenoside's 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), in the water for injection 500ml of the salt of ginsenoside, sodium chloride addition 30 DEG C～40 DEG C, stirring is to the completeest
After CL, the activated carbon of addition, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filters
Decarburization；
(4) step (3) gained filtrate configures by step (2) citric acid and/or liquor sodii citratis regulate pH
Value is 3.0～7.0, adds 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 citric acid, citric acid
Any one in sodium, or citric acid, sodium citrate are with arbitrary proportion proportioning；In step (2), add
Citric acid, one in sodium citrate, then make a kind of solution, as included citric acid, sodium citrate two
Kind, it is configured to solution for standby the most respectively；The salt of ginsenoside, the consumption of osmotic pressure regulator can use existing
The consumption of technology, adjusts 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, ginsenoside
In drug injection preparation, when using citric acid, sodium citrate as pH adjusting agent, medicinal liquid pH value is more steady
Fixed, ginsenoside's degradation material relatively prior art is substantially reduced, and uses other to increase clinical practice wind avoiding
In the case of the cosolvent of danger, ginsenoside injection is satisfactorily addressed and has used prior art products to exist
Storage process easily separates out tiny white point, white block, the problem of solution muddiness, it is ensured that ginsenoside notes
Penetrate the visible foreign matters detection keeping injection that liquid can be stable in storage process and meet drug standard
Regulation, it is simple to clinical application and popularization.
The present invention passes through creative work, to the tiny white point separated out in ginsenoside's injection, white block, molten
The reason that liquid is muddy is analyzed and studies, and determines that deposit is mainly raw material free alkali crystallize and a small amount of fall
Hydrolysis products, occurs that above-mentioned reason may have with acid used by the pH value of solution and pH adjusting agent, the kind of alkali
Close.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 risks, with solve this product in long-term storage and
Tiny white point, white block, the problem of solution muddiness is easily separated out under the conditions of winter low temperature.
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
It is limited to this.
Embodiment 1
A kind of preparation method of the medicinal composition for injections improving ginsenoside's drug injection preparation stability,
Comprise the steps: that (1) weighting raw materials is with ginsenoside's amount of calculation 0.1g～100g, sodium chloride 9.0g, Chinese holly
Rafter acid 1mg～2.0g, sodium citrate 1mg～2.0g；(2) citric acid, sodium citrate be configured to respectively 10%～
The solution of 20%, standby.(3) add in the water for injection 500ml of less than 40 DEG C, stirring to after being completely dissolved,
Add the activated carbon of 0.02% (g/ml), stir 15 minutes, filter decarburization.(4) filtrate citric acid or Chinese holly
Rafter acid sodium solution regulation pH value 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:
Citric acid, sodium citrate are configured to the solution of 10%～20% respectively, standby.Hydrochloric acid ginsenoside, chlorine
Change sodium and add in the water for injection 500ml of less than 40 DEG C, stir to after being completely dissolved, the work of addition 0.02%
Property charcoal (i.e. activated carbon dosage is 0.02g/100ml), stir 15 minutes, filter decarburization.Filtrate citric acid
Or liquor sodii citratis regulation pH value is 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 ginsenoside's drug injection preparation stability is by following
Prepared by step:
(1) weighting raw materials is with ginsenoside's amount of calculation 0.1g～100g, citric acid 1mg～2.0g, citric acid
Sodium 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's)
Activated carbon, stirs 15 minutes, filters decarburization.(4) filtrate citric acid or liquor sodii citratis regulation pH value
It is 3.0～7.0, adds the water for injection of less than 40 DEG C to 1000ml；(5) medical filtration is to clarification, fills
Dress, sterilizing, to obtain final product.
Composition and the content thereof of the concrete each component of the present embodiment are as follows:
Hydrochloric acid ginsenoside 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 ginsenoside adds
In the water for injection 500ml of less than 40 DEG C, stir to after being completely dissolved, add 0.02% activated carbon (the most alive
Property charcoal consumption be 0.02g/100ml), stir 15 minutes, filter decarburization.Filtrate citric acid or sodium citrate
Solution regulation pH value is 3.8～4.2, adds the water for injection of less than 40 DEG C to 1000ml.Medical filtration is extremely
Clarification, fill, sterilizing, to obtain final product.
Embodiment 3
Ginsenoside's sodium chloride injection stability comparative test
The visible foreign matters detection utilizing ginsenoside's sodium chloride injection obtained by the present invention meets drug quality mark
Accurate regulation, and stability of solution is fine, uses other to increase the cosolvent of clinical practice risks avoiding
In the case of, solve ginsenoside's sodium chloride injection and small particles, white block, molten easily occurs in storage process
The problems such as liquid is muddy.Utilize the ginsenoside's sodium chloride injection obtained by the present invention according to Chinese Pharmacopoeia 2005
The related request of year two annex Ⅺ Ⅹ C pharmaceutical preparation stability test guidelines of version, has investigated respectively
Place to place for 24 months, 40 DEG C for 25 DEG C and within 6 months, 60 DEG C, place 10 days, 0～5 DEG C of low temperature 20 days medicine of placement
Thing stability, result constant product quality at the conditions of the experiments described above, every Testing index all meets this quality
The regulation of amount standard.
The pharmacological results shows: utilize stable ginsenoside's 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 ginsenoside's 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, ginsenoside's drug injection preparation of the present invention can improve ginsenoside's note
Penetrate the clarity of liquid, particularly ginsenoside inject period of storage longer in the case of, it is possible to stable guarantor
The visible foreign matters detection holding injection meets the regulation of drug standard, solves ginsenoside's medicine and uses
Existing technical products occurs the problem that small particles, white block, solution are muddy in the case of period of storage is longer, can
To 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 (5)
1. the medicinal composition for injections improving ginsenoside's drug injection preparation stability, it is characterized in that, mainly it is dissolved in water for injection by the salt of ginsenoside, 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 ginsenoside's 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 ginsenoside's drug injection preparation stability the most according to claim 1, it is characterised in that the concentration of the salt of described ginsenoside is calculated as 10mg～10g/100ml with ginsenoside.
A kind of medicinal composition for injections improving ginsenoside's 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 ginsenoside's drug injection preparation stability the most according to claim 1, it is characterised in that described ginsenoside's drug injection preparation formulation is injection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610353138.9A CN105999278A (en) | 2016-05-24 | 2016-05-24 | Injecting medicine composition for improving stability of ginsenoside medicine injection |
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| CN201610353138.9A CN105999278A (en) | 2016-05-24 | 2016-05-24 | Injecting medicine composition for improving stability of ginsenoside medicine injection |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110559328A (en) * | 2019-11-01 | 2019-12-13 | 吉林省集安益盛药业股份有限公司 | A method for preparing total saponins of herba Herminii with 11 ginsenosides as fingerprint characteristic components |
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
- 2016-05-24 CN CN201610353138.9A patent/CN105999278A/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 (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110559328A (en) * | 2019-11-01 | 2019-12-13 | 吉林省集安益盛药业股份有限公司 | A method for preparing total saponins of herba Herminii with 11 ginsenosides as fingerprint characteristic components |
| CN110559328B (en) * | 2019-11-01 | 2021-04-30 | 吉林省集安益盛药业股份有限公司 | A method for preparing total saponins of herba Herminii with 11 ginsenosides as fingerprint characteristic components |
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Application publication date: 20161012 |
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