CN105878180A - Pharmaceutical composition for injection capable of improving stability of geniposide medicine injection preparation - Google Patents
Pharmaceutical composition for injection capable of improving stability of geniposide medicine injection preparation Download PDFInfo
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- CN105878180A CN105878180A CN201610293564.8A CN201610293564A CN105878180A CN 105878180 A CN105878180 A CN 105878180A CN 201610293564 A CN201610293564 A CN 201610293564A CN 105878180 A CN105878180 A CN 105878180A
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- Prior art keywords
- injection
- jasminoidin
- pharmaceutical composition
- geniposide
- citric acid
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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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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- 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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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a pharmaceutical composition for injection capable of improving the stability of a geniposide medicine injection preparation and a preparation method of the pharmaceutical composition. The pharmaceutical composition for injection is a pharmaceutical composition for injection, which is mainly prepared by dissolving a salt of geniposide to water for injection, and adding citric acid and/or sodium citrate as a PH adjuster to adjust the PH value of medical liquid, wherein the dosage of the citric acid and/or sodium citrate is 0.1mg to 200.0mg/100ml. According to the pharmaceutical composition for injection and the preparation method thereof disclosed by the invention, the pH value of the injection is more stable, geniposide degradation substances are greatly reduced compared with that of the prior art, the clarity of the geniposide injection is improved under the condition of avoiding the use of other cosolvent capable of increasing the clinical application risks, and especially the problems of small white spots, white blocks and turbid solution appearing when the geniposide injection adopting products of the prior art is stored for a long time are solved. The pharmaceutical composition can ensure that the inspection of foreign substance can accord with the provisions of drug quality standards, and is convenient for clinical medication and promotion.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to a kind of raising jasminoidin drug injection preparation is steady
Medicinal composition for injections qualitatively.
Background technology
Jasminoidin is to use high-tech production technology to extract essence from the dry mature fruit of Maguireothamnus speciosus Fructus Gardeniae
The product of system.Jasminoidin is iridoid glycoside compounds, different name geniposide, all Fructus Armeniacae Mume element Fructus Vitis viniferae
Glucosides geniposide.Jasminoidin has multiple use, the fermentation of different condition, can make natural edible and
Toner gardenia blue and gardenia red, be also the crude drug for treating the disease such as cardiovascular and cerebrovascular vessel, liver and gall and diabetes
Thing.Due to jasminoidin dissolubility extreme difference in aqueous, therefore it is made into jasminoidin hydrochlorate or jasminoidin
Phosphate is to increase its water solublity.Presently commercially available jasminoidin injection mainly has jasminoidin hydrochlorate, Fructus Gardeniae
The phosphatic injection with small volume of glycosides, and in jasminoidin hydrochlorate, jasminoidin phosphate solution, add Portugal
The high-capacity injection that grape sugar or sodium chloride are made as osmotic pressure regulator.But when preparing above-mentioned injection,
The pH value of medicinal liquid must be adjusted to be suitable for the certain limit that human injection is administered, and current document report uses
PH value regulator is sodium hydroxide solution or uses hydrochloric acid solution, phosphoric acid solution, but uses above-mentioned pH value
Jasminoidin injection prepared by regulator easily separate out under the conditions of long-term storage and winter low temperature tiny white point,
The precipitate such as white block, solution are muddy, 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 solving product
Etc. sedimentary problem.But polyoxyethylene sorbitan monoleate is owing to having the effect of haemolysis and blood pressure lowering, and at storage and high temperature
Sterilization process easily becomes sour, causes the injection clinical practice risk containing polyoxyethylene sorbitan monoleate higher, faced
Bed medication and popularization are made troubles.
Summary of the invention
The technical problem to be solved is to provide a kind of jasminoidin drug injection preparation stability of improving
Medicinal composition for injections.This medicinal composition for injections use 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
Adding stable, jasminoidin degradation material relatively prior art is substantially reduced, and uses other to increase clinical practice avoiding
In the case of the cosolvent of risk, jasminoidin injection is satisfactorily addressed low in long-term storage and winter
Tiny white point, white block, the problem of solution muddiness is easily separated out under the conditions of temperature.
The present invention solves the problems referred to above and be the technical scheme is that a kind of raising jasminoidin drug injection preparation
The medicinal composition for injections of stability, is mainly dissolved in water for injection by the salt of jasminoidin, adds osmotic pressure and adjusts
Joint agent, and add the injection that citric acid and/or sodium citrate are made as pH adjusting agent regulation medicinal liquid pH value
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 jasminoidin includes jasminoidin hydrochlorate, jasminoidin phosphate.
The concentration of the salt of described jasminoidin is calculated as 10mg～10g/100ml with jasminoidin.
Described medicinal liquid pH value is 3.0～6.0.
Described jasminoidin drug injection preparation formulation is injection.
The preparation method of the medicinal composition for injections of above-mentioned raising jasminoidin drug injection preparation stability, bag
Include following step:
(1) salt of jasminoidin is weighed with jasminoidin 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 jasminoidin, sodium chloride addition 30 DEG C～40 DEG C, stirring is to completely
After dissolving, the activated carbon of addition, described activated carbon dosage is 0.02g/100ml, stirs 15 minutes, filters de-
Carbon；
(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 jasminoidin, the consumption of osmotic pressure regulator can use existing skill
The consumption of art, 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, at jasminoidin medicine
In thing ejection preparation, when using citric acid, sodium citrate as pH adjusting agent, medicinal liquid pH value is more stable,
Jasminoidin degradation material relatively prior art is substantially reduced, and increases helping of clinical practice risks avoiding using other
In the case of solvent, jasminoidin injection is satisfactorily addressed and has used prior art products at storage process
In easily separate out tiny white point, white block, problem that solution is muddy, it is ensured that jasminoidin injection is in storage
During can be stable the visible foreign matters detection keeping injection meet the regulation of drug standard, it is simple to
Clinical application and popularization.
The present invention passes through creative work, to the tiny white point separated out in jasminoidin injection, white block, solution
Muddy reason is analyzed and studies, and determines that deposit is mainly raw material free alkali crystallize and a small amount of degraded
Product, occurs 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 is as pH adjusting agent, and uses citric acid as pH value counter regulation agent, is avoiding
In the case of using other to increase the cosolvent of clinical practice risk, to solve this product in long-term storage and winter
Tiny white point, white block, the problem of solution muddiness is easily separated out under cryogenic conditions.
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 jasminoidin drug injection preparation stability, bag
Include following step: (1) weighting raw materials is with jasminoidin 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 10%～20% respectively
Solution, standby.(3) adding in the water for injection 500ml of less than 40 DEG C, stirring, to after being completely dissolved, adds
Enter the activated carbon of 0.02% (g/ml), stir 15 minutes, filter decarburization.(4) filtrate citric acid or citron
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) medicine
Liquid is filtered until clear, fill, and 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 jasminoidin, chlorination
Sodium adds in the water for injection 500ml of less than 40 DEG C, stirs to after being completely dissolved, the activity of addition 0.02%
Charcoal (i.e. activated carbon dosage is 0.02g/100ml), stirs 15 minutes, filters decarburization.Filtrate citric acid or
Liquor sodii citratis regulation pH value is 3.8～4.2, adds the water for injection of less than 40 DEG C to 1000ml.Medicine
Liquid is filtered until clear, fill, and sterilizing to obtain final product.
Embodiment 2
Or, the medicinal composition for injections of above-mentioned raising jasminoidin drug injection preparation stability presses following step
Rapid preparation:
(1) weighting raw materials is with jasminoidin 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
Enter in the water for injection 500ml of less than 40 DEG C, stir to after being completely dissolved, add the work of 0.02% (g/ml)
Property charcoal, stir 15 minutes, filter 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 clarifying, 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 jasminoidin 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 jasminoidin 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
Jasminoidin sodium chloride injection stability comparative test
The visible foreign matters detection utilizing jasminoidin sodium chloride injection obtained by the present invention meets drug standard
Regulation, and stability of solution is fine, uses other to increase the feelings of the cosolvent of clinical practice risks avoiding
Under condition, solve jasminoidin sodium chloride injection in storage process, easily occur that small particles, white block, solution are muddy
The problem such as turbid.Utilize the jasminoidin sodium chloride injection obtained by the present invention according to China's coastal port two
The related request of portion's annex Ⅺ Ⅹ C pharmaceutical preparation stability test guideline, has investigated respectively and has put at 25 DEG C
Put to place for 24 months, 40 DEG C and within 6 months, 60 DEG C, place 10 days, 0～5 DEG C of low temperature 20 days drug substance stable of placement
Property, 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 the stable jasminoidin sodium chloride injection obtained by the present invention without molten
Courageous and upright, 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 jasminoidin 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 jasminoidin drug injection preparation of the present invention can improve jasminoidin injection
Clarity, particularly in the case of jasminoidin injection period of storage is longer, it is possible to stable holding injection
The visible foreign matters detection of liquid meets the regulation of drug standard, solves jasminoidin medicine and uses existing technology to produce
Product occur the problem that small particles, white block, solution are muddy in the case of period of storage is longer, it is ensured that produce
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 jasminoidin drug injection preparation stability, it is characterized in that, mainly it is dissolved in water for injection by the salt of jasminoidin, 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 jasminoidin 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 jasminoidin drug injection preparation stability the most according to claim 1, it is characterised in that the concentration of the salt of described jasminoidin is calculated as 10mg～10g/100ml with jasminoidin.
A kind of medicinal composition for injections improving jasminoidin 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 jasminoidin drug injection preparation stability the most according to claim 1, it is characterised in that described jasminoidin drug injection preparation formulation is injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610293564.8A CN105878180A (en) | 2016-05-05 | 2016-05-05 | Pharmaceutical composition for injection capable of improving stability of geniposide medicine injection preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610293564.8A CN105878180A (en) | 2016-05-05 | 2016-05-05 | Pharmaceutical composition for injection capable of improving stability of geniposide medicine injection preparation |
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| CN105878180A true CN105878180A (en) | 2016-08-24 |
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| CN201610293564.8A Withdrawn CN105878180A (en) | 2016-05-05 | 2016-05-05 | Pharmaceutical composition for injection capable of improving stability of geniposide medicine injection preparation |
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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
- 2016-05-05 CN CN201610293564.8A patent/CN105878180A/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 |
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Application publication date: 20160824 |
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