CN106344505A - Pharmaceutical composition capable of improving safety of compound obtuseleaf erycibe stem injection - Google Patents

Pharmaceutical composition capable of improving safety of compound obtuseleaf erycibe stem injection Download PDF

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CN106344505A
CN106344505A CN201610968060.1A CN201610968060A CN106344505A CN 106344505 A CN106344505 A CN 106344505A CN 201610968060 A CN201610968060 A CN 201610968060A CN 106344505 A CN106344505 A CN 106344505A
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pharmaceutical composition
injection
dinggongteng
radix
compound recipe
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付裕
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Chengdu First Biotech Co Ltd
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    • 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)
    • 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)
    • A61K36/39—Convolvulaceae (Morning-glory family), e.g. bindweed
    • 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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/708—Rheum (rhubarb)
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • 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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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a pharmaceutical composition capable of improving the safety of a compound obtuseleaf erycibe stem injection. The pharmaceutical composition is a pharmaceutical composition for injection, prepared from obtuseleaf erycibe stem extract, rheum officinale extract, pubescent holly root extract and hexafluorobutyl methacrylate. According to the invention, a cosolvent, polysorbate 80, which has potential safety hazards and influences the product quality in the compound obtuseleaf erycibe stem injection is replaced with a cosolvent with better safety and more obvious solubilizing effect, the hexafluorobutyl methacrylate is higher in safety than the polysorbate 80 and is low in usage amount, the probability and risk of causing adverse reactions of the drug can be reduced, and the clinical medication safety is improved.

Description

A kind of pharmaceutical composition improving compound recipe Dinggongteng Injection safety
Technical field
A kind of the invention belongs to pharmaceutical technology field, in particular it relates to medicine improving compound recipe Dinggongteng Injection safety Compositions.
Background technology
Compound recipe Dinggongteng Injection standard is recorded and is issued drug standard (Traditional Chinese medicine historical preparation) in Ministry of Public Health, and crude drug is that fourth is public Rattan, Radix Et Rhizoma Rhei, Radix Ilicis Pubescentiss, belong to Chinese medicine injection.There is promoting blood circulation to restore menstrual flow, effect of stasis-dispelling and pain-killing.It is clinically used for treating dysmenorrhea, warp Close, injury from falling down, rheumatic arthralgia etc..
In China in wide clinical application for many years, clinical efficacy has obtained the good of doctor and patient to compound recipe Dinggongteng Injection Comment.But in recent years, the Reporting of harms of Chinese medicine injection clinical practice is on the rise, have impact on and there is Chinese Medicine characteristic The development of Chinese medicine injection.Domestic experts and scholars have carried out numerous studies to the untoward reaction of Chinese medicine injection, document report its The generation of untoward reaction is had very with the cosolvent polyoxyethylene sorbitan monoleate (Tween 80) of the presence potential safety hazard of addition in Chinese medicine injection Big relation.Due to Chinese medicine injection complicated component, solute easily occurs in storage and autoclaving process and separates out and affect clear The problems such as lightness, solution ph are decreased obviously, therefore adds polyoxyethylene sorbitan monoleate (Tween 80) in such injection and makees hydrotropy Agent, adds the solubilization-aid effect of other cosolvents then inconspicuous.But polyoxyethylene sorbitan monoleate (Tween 80) is immature due to process for refining, Easily become sour in storage and autoclaving process, lead to impurity content high it is difficult to reach injection standard, polyoxyethylene sorbitan monoleate (is told Temperature 80) inherently there are stronger hemolytic and anaphylaxis, apply increased in injection occur untoward reaction probability and Risk.In addition, in sterilizing and storage process itself, Chinese medicine injection also has that solution ph is decreased obviously, and poly- Pyrusussuriensiss Ester 80 (Tween 80) and easily becoming sour, more accelerates the decline of the ph value of medicinal liquid.The compound recipe Caulis Erycibess injection of domestic production at present Also add polyoxyethylene sorbitan monoleate (Tween 80) in liquid and make cosolvent, be faced with same problem.
In view of the foregoing, find the poly- mountain that safety is more preferable, poor stability replaced by the more obvious cosolvent of solubilization-aid effect Pear ester 80 (Tween 80) is this injection urgent problem.
Content of the invention
The technical problem to be solved is to provide that a kind of safety is more preferable, solubilization-aid effect more obviously improves compound recipe The pharmaceutical composition of Dinggongteng Injection safety.
The present invention solves above-mentioned technical problem and be the technical scheme is that a kind of raising compound recipe Dinggongteng Injection safety The pharmaceutical composition of property, mainly by Caulis Erycibes extract, Radix Et Rhizoma Rhei extract, Radix Ilicis Pubescentis extract and Hexafluorobutyl mathacrylate The injection pharmaceutical composition made.
Specifically, the consumption of Hexafluorobutyl mathacrylate is 0.005g～5.0g/100ml；Methacrylic acid hexafluoro fourth The consumption of ester is preferably 0.05g～1.0g/100ml.
Polyoxyethylene sorbitan monoleate is also included, Hexafluorobutyl mathacrylate is from polyoxyethylene sorbitan monoleate by different in aforementioned pharmaceutical compositions Ratio is combined and is made cosolvent, and Hexafluorobutyl mathacrylate is 0.005g～5.0g/ with the usage ratio of polyoxyethylene sorbitan monoleate 100ml:0.001g～2.0g/100ml.
Described pharmaceutical composition dosage form is injection, powder pin or lyophilizing.
A kind of preparation method improving compound recipe Dinggongteng Injection safety pharmaceutical composition, comprises the steps:
(1) compound recipe Dinggongteng Injection raw medicinal material Caulis Erycibess 100g, Radix Et Rhizoma Rhei 100g, Radix Ilicis Pubescentiss 100g, cosolvent 2.0g；
(2) Caulis Erycibess, Radix Et Rhizoma Rhei add water to cook secondary, 2 hours every time, collecting decoction, plus ethanol filtering and concentrating, plus 3 times amount Water, is sufficiently stirred for, cold preservation 48 hours, filtration, and filtrate reduced in volume to relative density is about 1.15, and medicinal liquid is standby；
(3) Radix Ilicis Pubescentiss add water to cook secondary, 1 hour every time, collecting decoction, filtration, concentrate filtrate, let cool, plus ethanol make Containing amount of alcohol be 65%, stand overnight, filtration, filtrate reduced in volume to relative density be 1.20, plus ethanol make containing amount of alcohol be 70%, stand overnight, filtration, it is 1.30 that filtrate is concentrated into relative density, plus 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filter Cross, it is 1.15 that filtrate is concentrated into relative density,
(4) merge with above-mentioned all medicinal liquids, plus 2 times amount water, it is sufficiently stirred for, cold preservation 24 hours, filtration, filtrate adds hydrotropy Agent and water for injection are configured to 1000ml solution, stir evenly, and the relative density of above-mentioned each filtrate is relative density when 80 DEG C；
(5) with sodium hydroxide solution regulation solution ph to 6.5-8.5；
(6) filter, fill, sterilizing, obtain final product.
In order to the method for the present invention is better achieved, further, in described step (1), cosolvent is by methacrylic acid Hexafluoro butyl ester is formed with polyoxyethylene sorbitan monoleate, and wherein the content of Hexafluorobutyl mathacrylate is 0.005g～2.0g, balance of poly- Pyrusussuriensiss ester 80.
In order to the method for the present invention is better achieved, further, in described step (2), plus the mistake of ethanol filtering and concentrating Cheng Wei, first filters to get filtrate, filtrate reduced in volume to relative density be 1.27～1.30, let cool, plus ethanol make containing amount of alcohol be 65%, stand overnight, filtration, decompression filtrate recycling ethanol is simultaneously concentrated into relative density for 1.30.
In order to the method for the present invention is better achieved, further, in described step (3), filtrate is concentrated into relative density For 1.25～1.30.
In order to the method for the present invention is better achieved, further, in described step (5), the sodium hydroxide solution of use Mass percent be 20%.
In order to the method for the present invention is better achieved, further, in described step (6), solution uses microporous filter membrane mistake Filter.
The present invention, by substantial amounts of experimentation, finds a kind of Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol) it is the preferable substitute products of polyoxyethylene sorbitan monoleate.Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol) recorded in European Pharmacopoeia (ep5.5), Deutscher Arzneibucses and British Pharmacopoeia, can be used for the increasing of ejection preparation Solvent.The pharmacological toxicology experimental data of document report shows that its toxicity is significantly lower than polyoxyethylene sorbitan monoleate (Tween 80).In addition we By substantial amounts of experimental studies have found that, Polyethylene Glycol (peg) 12-hydroxy stearic acid ester when reaching identical solubilization-aid effect (solutol) amount ratio polyoxyethylene sorbitan monoleate (Tween 80) low, more improve Drug safety.
The pharmacological toxicology experimental data of document report shows Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol) safety higher than polyoxyethylene sorbitan monoleate (Tween 80), its toxicity (sees below significantly lower than polyoxyethylene sorbitan monoleate (Tween 80) Table 1-3).In compound recipe Dinggongteng Injection, (0.5g/100ml) Polyethylene Glycol (peg) ten dihydroxy using equivalent are hard respectively Fat acid ester (solutol) and polyoxyethylene sorbitan monoleate (Tween 80), safety experiment comparative study result shows, using etc. (0.5g/100ml) Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol of amount) group is in hemolytic, stimulation Property, anaphylaxis and the toxicity aspect such as reduce blood pressure are all substantially low than being organized using polyoxyethylene sorbitan monoleate (Tween 80), by this Bright considerably reduce probability and the risk that compound recipe Dinggongteng Injection occurs untoward reaction in clinical practice, improve clinical application Safety.
To sum up, the invention has the beneficial effects as follows: provide that a kind of safety is more preferable, the more obvious cosolvent of solubilization-aid effect is replaced There is potential safety hazard and the cosolvent polyoxyethylene sorbitan monoleate (Tween 80) of impact product quality in compound recipe Dinggongteng Injection；Poly- second two Alcohol (peg) 12-hydroxy stearic acid ester (solutol) safety higher than polyoxyethylene sorbitan monoleate (Tween 80) and use Amount is lower, reduces probability and the risk that medicine occurs untoward reaction, improves the safety of clinical application.
Specific embodiment
Embodiment 1
Preparation method: Caulis Erycibess, Radix Et Rhizoma Rhei add water to cook secondary, 2 hours every time, collecting decoction, filtration, filtrate reduced in volume It is 1.27～1.30 (80 DEG C) to relative density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, stands overnight, filtration, filtrate subtracts Push back receipts ethanol and be concentrated into relative density for 1.30 (80 DEG C), plus 3 times amount water, it is sufficiently stirred for, cold preservation 48 hours, filtration, filter Liquid is evaporated to relative density and is about 1.15 (80 DEG C), and medicinal liquid is standby；Radix Ilicis Pubescentiss add water to cook secondary, 1 hour every time, merge Decocting liquid, filtration, it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, quiet Put overnight, filtration, filtrate reduced in volume to relative density is 1.20 (80 DEG C), plus ethanol makes containing amount of alcohol to be 70%, stands Night, filtration, it is 1.30 (80 DEG C) that filtrate is concentrated into relative density, plus 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filtration, filter It is 1.15 (80 DEG C) that liquid is concentrated into relative density, merges with above-mentioned medicinal liquid, plus 2 times amount water, is sufficiently stirred for, cold preservation 24 hours, filter Cross, filtrate adds Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol) make cosolvent and water for injection It is configured to 1000ml solution.Stir evenly.With 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.By above-mentioned solution through micro- Hole filter membrane filtration.Fill, sterilizing, obtain final product.
Embodiment 2
Preparation method: Caulis Erycibess, Radix Et Rhizoma Rhei add water to cook secondary, 2 hours every time, collecting decoction, filtration, filtrate reduced in volume It is 1.27～1.30 (80 DEG C) to relative density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, stands overnight, filtration, filtrate subtracts Push back receipts ethanol and be concentrated into relative density for 1.30 (80 DEG C), plus 3 times amount water, it is sufficiently stirred for, cold preservation 48 hours, filtration, filter Liquid is evaporated to relative density and is about 1.15 (80 DEG C), and medicinal liquid is standby；Radix Ilicis Pubescentiss add water to cook secondary, 1 hour every time, merge Decocting liquid, filtration, it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, quiet Put overnight, filtration, filtrate reduced in volume to relative density is 1.20 (80 DEG C), plus ethanol makes containing amount of alcohol to be 70%, stands Night, filtration, it is 1.30 (80 DEG C) that filtrate is concentrated into relative density, plus 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filtration, filter It is 1.15 (80 DEG C) that liquid is concentrated into relative density, merges with above-mentioned medicinal liquid, plus 2 times amount water, is sufficiently stirred for, cold preservation 24 hours, filter Cross, filtrate adds Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol) with tween 80 make cosolvent and Water for injection is configured to 1000ml solution.Stir evenly.With 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.Will be above-mentioned Solution filters through microporous filter membrane.Fill, sterilizing, obtain final product.
Embodiment 3
Preparation method: Caulis Erycibess, Radix Et Rhizoma Rhei add water to cook secondary, 2 hours every time, collecting decoction, filtration, filtrate reduced in volume It is 1.27～1.30 (80 DEG C) to relative density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, stands overnight, filtration, filtrate subtracts Push back receipts ethanol and be concentrated into relative density for 1.30 (80 DEG C), plus 3 times amount water, it is sufficiently stirred for, cold preservation 48 hours, filtration, filter Liquid is evaporated to relative density and is about 1.15 (80 DEG C), and medicinal liquid is standby；Radix Ilicis Pubescentiss add water to cook secondary, 1 hour every time, merge Decocting liquid, filtration, it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, quiet Put overnight, filtration, filtrate reduced in volume to relative density is 1.20 (80 DEG C), plus ethanol makes containing amount of alcohol to be 70%, stands Night, filtration, it is 1.30 (80 DEG C) that filtrate is concentrated into relative density, plus 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filtration, filter It is 1.15 (80 DEG C) that liquid is concentrated into relative density, merges with above-mentioned medicinal liquid, plus 2 times amount water, is sufficiently stirred for, cold preservation 24 hours, filter Cross, filtrate adds Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol) make cosolvent and water for injection is joined Make solution.Stir evenly.With 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.Above-mentioned solution is filtered through microporous filter membrane Cross.It is distributed into 1000, lyophilization, obtain final product.
Embodiment 4:
The Caulis Erycibes extract of the present invention, Radix Et Rhizoma Rhei extract, Radix Ilicis Pubescentis extract and Polyethylene Glycol (peg) ten dihydroxy are hard Fat acid ester (solutol) the injection pharmaceutical composition made can be achieved through the following technical solutions:
(1) compound recipe Dinggongteng Injection raw medicinal material Caulis Erycibess 100g, Radix Et Rhizoma Rhei 100g, Radix Ilicis Pubescentiss 100g, Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol)2.0g；
(2) Caulis Erycibess, Radix Et Rhizoma Rhei add water to cook secondary, 2 hours every time, collecting decoction, filtration, filtrate reduced in volume is to relatively Density is 1.27～1.30 (80 DEG C), lets cool, plus ethanol makes containing amount of alcohol to be 65%, stands overnight, filtration, filtrate decompression reclaims Ethanol is simultaneously concentrated into relative density for 1.30 (80 DEG C), plus 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filtration, filtrate decompression It is concentrated into relative density and is about 1.15 (80 DEG C), medicinal liquid is standby；Radix Ilicis Pubescentiss add water to cook secondary, 1 hour every time, collecting decoction, Filtration, it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, stands Night, filtration, filtrate reduced in volume to relative density is 1.20 (80 DEG C), plus ethanol makes containing amount of alcohol to be 70%, stands overnight, filter Cross, it is 1.30 (80 DEG C) that filtrate is concentrated into relative density, plus 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filtration, and filtrate concentrates It is 1.15 (80 DEG C) to relative density, merge with above-mentioned medicinal liquid, plus 2 times amount water, it is sufficiently stirred for, cold preservation 24 hours, filtration, filtrate Add Polyethylene Glycol (peg) 12-hydroxy stearic acid ester (solutol) make cosolvent and water for injection is configured to 1000ml solution.Stir evenly.
(3) with 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.
(4) above-mentioned solution is filtered through microporous filter membrane.
(5) fill, sterilizing, obtain final product.
In the present invention, cosolvent can be Hexafluorobutyl mathacrylate, and its consumption is in 0.005g～5.0g/100ml Arbitrary value, such as 0.005g/100ml, 0.01g/100ml, 0.05g/100ml, 1.0g/100ml, 5.0g/100ml etc.；Hydrotropy Agent can also be made up of with polyoxyethylene sorbitan monoleate Hexafluorobutyl mathacrylate, and its usage ratio is 0.005g～5.0g/100ml: 0.001g～2.0g/100ml.

Claims (6)

1. a kind of pharmaceutical composition improving compound recipe Dinggongteng Injection safety is it is characterised in that mainly extracted by Caulis Erycibess The injection pharmaceutical composition that thing, Radix Et Rhizoma Rhei extract, Radix Ilicis Pubescentis extract and Hexafluorobutyl mathacrylate are made.
2. the pharmaceutical composition improving compound recipe Dinggongteng Injection safety according to claim 1 is it is characterised in that every 100ml solution contains and is equivalent to the Caulis Erycibes extract of 5-15g Caulis Erycibes, the Radix Et Rhizoma Rhei extract of 5-15g rhubarb medicinal material, 5- The Radix Ilicis Pubescentis extract of 15g Radix Ilicis Pubescentiss medical material, Caulis Erycibess, Radix Et Rhizoma Rhei, the usage ratio of Radix Ilicis Pubescentiss medical material are 1:1:1.
3. the pharmaceutical composition improving compound recipe Dinggongteng Injection safety according to claim 1 is it is characterised in that institute The consumption stating Hexafluorobutyl mathacrylate is 0.005g～5.0g/100ml.
4. the pharmaceutical composition improving compound recipe Dinggongteng Injection safety according to claim 3 is it is characterised in that institute The consumption stating Hexafluorobutyl mathacrylate is 0.05g～1.0g/100ml.
5. the pharmaceutical composition improving compound recipe Dinggongteng Injection safety according to claim 1 is it is characterised in that institute State and in pharmaceutical composition, also include polyoxyethylene sorbitan monoleate, Hexafluorobutyl mathacrylate combines work with polyoxyethylene sorbitan monoleate by different proportion Cosolvent, the usage ratio of Hexafluorobutyl mathacrylate and polyoxyethylene sorbitan monoleate be 0.005g～5.0g/100ml:0.001g～ 2.0g/100ml.
6. the pharmaceutical composition of the raising compound recipe Dinggongteng Injection safety according to claim 1 to 5 any one, its It is characterised by, described pharmaceutical composition dosage form is injection, powder pin or lyophilizing.
CN201610968060.1A 2016-11-06 2016-11-06 Pharmaceutical composition capable of improving safety of compound obtuseleaf erycibe stem injection Withdrawn CN106344505A (en)

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CN201610968060.1A CN106344505A (en) 2016-11-06 2016-11-06 Pharmaceutical composition capable of improving safety of compound obtuseleaf erycibe stem injection

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