CN106176587A - A kind of medicinal composition for injections improving naringenin drug injection preparation stability - Google Patents
A kind of medicinal composition for injections improving naringenin drug injection preparation stability Download PDFInfo
- Publication number
- CN106176587A CN106176587A CN201610611436.3A CN201610611436A CN106176587A CN 106176587 A CN106176587 A CN 106176587A CN 201610611436 A CN201610611436 A CN 201610611436A CN 106176587 A CN106176587 A CN 106176587A
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- China
- Prior art keywords
- naringenin
- injection
- medicinal composition
- injections
- drug injection
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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
-
- 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
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
- 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 a kind of medicinal composition for injections improving naringenin drug injection preparation stability and preparation method thereof.This medicinal composition for injections is mainly dissolved in water for injection by the salt of naringenin, adding the medicinal composition for injections that tartaric acid and/or sodium tartrate are made as pH adjusting agent regulation medicinal liquid pH value, the consumption of described tartaric acid and/or sodium tartrate is 30mg～250.0mg/100ml.The present invention can make this injection pH value more stable, naringenin degradation material relatively prior art is substantially reduced, in the case of avoiding using other to increase the cosolvent of clinical practice risk, improve the clarity of naringenin injection, particularly solving naringenin injection uses prior art 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.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to a kind of naringenin drug injection preparation stability of improving
Medicinal composition for injections.
Background technology
Naringenin is the glycoside unit of naringin, belongs to flavanone kind composition, has antibacterial, antiinflammatory, removing free radical, antioxygen
Change, eliminating phlegm and stopping cough, blood fat reducing, anticancer antitumor, spasmolytic and function of gallbladder promoting, prevent and treat hepatopathy, anti-platelet clotting, anti-medicated porridge sample
Arteriosclerosis etc. act on, and can be widely used in the field such as medicine, food.
Due to naringenin dissolubility extreme difference in aqueous, therefore it is made into naringenin hydrochlorate or naringenin phosphate
To increase its water solublity.Presently commercially available naringenin injection mainly has the phosphatic low capacity of naringenin hydrochlorate, naringenin
Injection, and in naringenin hydrochlorate, naringenin 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 naringenin 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 naringenin drug injection preparation stability
Pharmaceutical composition.This medicinal composition for injections employing tartaric acid, sodium tartrate are as pH adjusting agent, and pass through creative labor
When dynamic discovery uses tartaric acid, sodium tartrate as pH adjusting agent, medicinal liquid pH value is more stable, and naringenin 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
Naringenin injection easily separates out tiny white point, white block, the problem of solution muddiness under the conditions of storage for a long time and winter low temperature.
The present invention solves the problems referred to above and be the technical scheme is that a kind of raising naringenin drug injection preparation stability
Medicinal composition for injections, be mainly dissolved in water for injection by the salt of naringenin, add osmotic pressure regulator, and add tartaric acid
And/or the medicinal composition for injections that sodium tartrate is made as pH adjusting agent regulation medicinal liquid pH value, described tartaric acid and/or wine
The consumption of stone acid sodium is 30mg～250.0mg/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 naringenin includes naringenin hydrochlorate, naringenin phosphate.
The concentration of the salt of described naringenin is calculated as 10mg～10g/100ml with naringenin.
Described medicinal liquid pH value is 3.0～8.6.
Described naringenin drug injection preparation formulation is injection.
The preparation method of the medicinal composition for injections of above-mentioned raising naringenin drug injection preparation stability, including following
Step:
(1) salt of naringenin is weighed with naringenin amount of calculation 30g～100g, tartaric acid and/or sodium tartrate 5.0mg～15.0g；
(2) tartaric acid, sodium tartrate are configured to the solution of 40g/100ml～60g/100ml respectively, standby；
(3) salt of naringenin, sodium chloride add in the water for injection 500ml of 10 DEG C～25 DEG C, stir to after being completely dissolved, add
The activated carbon entered, described activated carbon dosage is 10g/100ml, stirs 35 minutes, filters decarburization；
(4) step (3) gained filtrate step (2) configures tartaric acid and/or sodium tartrate solution regulation pH value be 3.0～
7.0, add the water for injection of less than 40 DEG C (20 DEG C～37 DEG C) to 1600ml；
(5) by step (4) gained medical filtration to clarification, fill, sterilizing, to obtain final product.
Described osmotic pressure regulator is sodium dihydrogen phosphate.
In such scheme, what addition tartaric acid and/or sodium tartrate referred to addition can be in tartaric acid, sodium tartrate
Any one, or tartaric acid, sodium tartrate are with arbitrary proportion proportioning；In step (2), the tartaric acid of addition, sodium tartrate
In one, then make a kind of solution, as included tartaric acid, sodium tartrate two kinds, be configured to solution for standby the most respectively；Naringenin
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 naringenin drug injection system
In agent, when using tartaric acid, sodium tartrate as pH adjusting agent, medicinal liquid pH value is more stable, and naringenin 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
Naringenin 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 naringenin 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 naringenin 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 tartrate is as pH adjusting agent,
And use tartaric 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 naringenin drug injection preparation stability, including following step
Rapid: (1) weighs the salt of naringenin with naringenin amount of calculation 30g～100g, tartaric acid and/or sodium tartrate 5.0mg～15.0g；
(2) tartaric acid, sodium tartrate are configured to the solution of 40g/100ml～60g/100ml respectively, standby；(3) naringenin salt,
Sodium chloride adds in the water for injection 500ml of 10 DEG C～25 DEG C, stirs to after being completely dissolved, the activated carbon of addition, described activity
Charcoal consumption is 10g/100ml, stirs 35 minutes, filters decarburization；(4) tartaric acid that step (3) gained filtrate configures by step (2)
And/or sodium tartrate solution regulation pH value is 3.0～7.0, add the water for injection of less than 40 DEG C (20 DEG C～37 DEG C) extremely
1600ml；(5) by step (4) gained 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 naringenin 38g
Sodium dihydrogen phosphate 10g
Tartaric acid 5g
Sodium tartrate 5g
Embodiment 2
Or, the medicinal composition for injections of above-mentioned raising naringenin drug injection preparation stability is prepared according to the following steps:
(1) salt of naringenin is weighed with naringenin amount of calculation 30g～100g, tartaric acid and/or sodium tartrate 5.0mg～15.0g；
(2) tartaric acid, sodium tartrate are configured to the solution of 40g/100ml～60g/100ml respectively, standby；(3) naringenin salt,
Sodium chloride adds in the water for injection 500ml of 10 DEG C～25 DEG C, stirs to after being completely dissolved, the activated carbon of addition, described activity
Charcoal consumption is 10g/100ml, stirs 35 minutes, filters decarburization；(4) tartaric acid that step (3) gained filtrate configures by step (2)
And/or sodium tartrate solution regulation pH value is 3.0～7.0, add the water for injection of less than 40 DEG C (20 DEG C～37 DEG C) extremely
1600ml；(5) by step (4) gained 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 naringenin 80g
Tartaric acid 15.0g
Sodium tartrate 15.0g
Embodiment 3
Naringenin sodium chloride injection stability comparative test
The visible foreign matters detection utilizing naringenin 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 naringenin chlorine
Change sodium injection and the problems such as small particles, white block, solution are muddy easily occur in storage process.Investigate respectively and placed 24 at 25 DEG C
Within individual month, 40 DEG C, placing and within 6 months, 60 DEG C, place 30 days, 0～5 DEG C of low temperature 50 days medicine stability of placement, result is at above-mentioned test bar
Constant product quality under part, every Testing index all meets the regulation of this product quality standard.
The pharmacological results shows: utilize stable naringenin sodium chloride injection obtained by the present invention without hemolytic,
Without anaphylaxis, nonirritant, meet the requirement of drug administration by injection.
According to the above results, the naringenin drug injection preparation of the present invention can improve the clear and bright of naringenin injection
Degree, particularly in the case of naringenin injection period of storage is longer, it is possible to the stable visible foreign matters detection keeping injection
Meet the regulation of drug standard, solve naringenin medicine and use existing technical products to go out in the case of period of storage is longer
Existing small particles, white block, the problem of solution muddiness, it is ensured that the visible foreign matters inspection of product meets the rule of drug standard
Fixed, 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 naringenin drug injection preparation stability, it is characterised in that main by Fructus Citri grandis
The salt of Pi Su is dissolved in water for injection, adds the note that tartaric acid and/or sodium tartrate are made as pH adjusting agent regulation medicinal liquid pH value
Penetrating pharmaceutical composition, the consumption of described tartaric acid and/or sodium tartrate is 30mg～250.0mg/100ml.
A kind of medicinal composition for injections improving naringenin drug injection preparation stability the most 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.
A kind of medicinal composition for injections improving naringenin drug injection preparation stability the most according to claim 1,
It is characterized in that, the salt of described naringenin includes naringenin hydrochlorate, naringenin phosphate.
4. according to a kind of injectable drug combination improving naringenin drug injection preparation stability described in claim 1 or 3
Thing, it is characterised in that the concentration of the salt of described naringenin is calculated as 10mg～10g/100ml with naringenin.
A kind of medicinal composition for injections improving naringenin drug injection preparation stability the most according to claim 1,
It is characterized in that, described medicinal liquid pH value is 3.0～8.6.
A kind of medicinal composition for injections improving naringenin drug injection preparation stability the most according to claim 1,
It is characterized in that, described naringenin drug injection preparation formulation is injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610611436.3A CN106176587A (en) | 2016-07-30 | 2016-07-30 | A kind of medicinal composition for injections improving naringenin drug injection preparation stability |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610611436.3A CN106176587A (en) | 2016-07-30 | 2016-07-30 | A kind of medicinal composition for injections improving naringenin drug injection preparation stability |
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| Publication Number | Publication Date |
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| CN106176587A true CN106176587A (en) | 2016-12-07 |
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| CN201610611436.3A Withdrawn CN106176587A (en) | 2016-07-30 | 2016-07-30 | A kind of medicinal composition for injections improving naringenin drug injection preparation stability |
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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 |
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2016
- 2016-07-30 CN CN201610611436.3A patent/CN106176587A/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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| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
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| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20161207 |