CN106389319A - Preparation method of pharmaceutical composition capable of improving safety of compound herba andrographis injection - Google Patents
Preparation method of pharmaceutical composition capable of improving safety of compound herba andrographis injection Download PDFInfo
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- CN106389319A CN106389319A CN201610968052.7A CN201610968052A CN106389319A CN 106389319 A CN106389319 A CN 106389319A CN 201610968052 A CN201610968052 A CN 201610968052A CN 106389319 A CN106389319 A CN 106389319A
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- 238000002347 injection Methods 0.000 title claims abstract description 37
- 239000007924 injection Substances 0.000 title claims abstract description 37
- 150000001875 compounds Chemical class 0.000 title claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 241000746375 Andrographis Species 0.000 title claims abstract description 15
- 239000006184 cosolvent Substances 0.000 claims abstract description 19
- 239000010231 banlangen Substances 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 75
- 239000000706 filtrate Substances 0.000 claims description 47
- 238000001914 filtration Methods 0.000 claims description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 28
- 239000007788 liquid Substances 0.000 claims description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 21
- 244000118350 Andrographis paniculata Species 0.000 claims description 19
- -1 Hexafluorobutyl Chemical group 0.000 claims description 19
- 238000004321 preservation Methods 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 7
- 230000033228 biological regulation Effects 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 230000001954 sterilising effect Effects 0.000 claims description 6
- 239000008215 water for injection Substances 0.000 claims description 5
- 230000006837 decompression Effects 0.000 claims description 4
- 239000012141 concentrate Substances 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000004064 recycling Methods 0.000 claims description 2
- DEQJNIVTRAWAMD-UHFFFAOYSA-N 1,1,2,4,4,4-hexafluorobutyl prop-2-enoate Chemical compound FC(F)(F)CC(F)C(F)(F)OC(=O)C=C DEQJNIVTRAWAMD-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000012982 microporous membrane Substances 0.000 claims 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 abstract description 17
- 229920000053 polysorbate 80 Polymers 0.000 abstract description 17
- 239000003814 drug Substances 0.000 abstract description 16
- 239000000284 extract Substances 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- LCPUCXXYIYXLJY-UHFFFAOYSA-N 1,1,2,4,4,4-hexafluorobutyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(F)(F)C(F)CC(F)(F)F LCPUCXXYIYXLJY-UHFFFAOYSA-N 0.000 abstract 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 abstract 2
- 229940068968 polysorbate 80 Drugs 0.000 abstract 2
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 241000218202 Coptis Species 0.000 abstract 1
- 235000002991 Coptis groenlandica Nutrition 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 230000007928 solubilization Effects 0.000 abstract 1
- 238000005063 solubilization Methods 0.000 abstract 1
- 239000002202 Polyethylene glycol Substances 0.000 description 25
- 229920001223 polyethylene glycol Polymers 0.000 description 25
- 229940114072 12-hydroxystearic acid Drugs 0.000 description 11
- ULQISTXYYBZJSJ-UHFFFAOYSA-N R-12-HOA Natural products CCCCCCC(O)CCCCCCCCCCC(O)=O ULQISTXYYBZJSJ-UHFFFAOYSA-N 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 244000173166 Pyrus ussuriensis Species 0.000 description 2
- 235000011572 Pyrus ussuriensis Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 239000009413 Chuanxinlian Substances 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 240000002853 Nelumbo nucifera Species 0.000 description 1
- 235000006508 Nelumbo nucifera Nutrition 0.000 description 1
- 235000006510 Nelumbo pentapetala Nutrition 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- OPCRGEVPIBLWAY-QNRZBPGKSA-N ethyl (2E,4Z)-deca-2,4-dienoate Chemical compound CCCCC\C=C/C=C/C(=O)OCC OPCRGEVPIBLWAY-QNRZBPGKSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000003119 painkilling effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
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
-
- 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)
- A61K36/19—Acanthaceae (Acanthus family)
-
- 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)
- A61K36/19—Acanthaceae (Acanthus family)
- A61K36/195—Strobilanthes
-
- 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)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
- A61K36/315—Isatis, e.g. Dyer's woad
-
- 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)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
- A61K36/718—Coptis (goldthread)
-
- 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
- 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
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
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Abstract
The invention discloses a preparation method of a pharmaceutical composition capable of improving the safety of a compound herba andrographis injection. The pharmaceutical composition for injection is mainly prepared from a herba andrographis extract, a coptis root extract, a radix isatidis extract and hexafluorobutyl methacrylate. Cosolvent with the better safety and the more obvious solubilization effect is adopted to replace cosolvent polysorbate 80 which has potential safety hazards and influences the product quality in a compound herba andrographis injection, the safety of hexafluorobutyl methacrylate is higher than that of polysorbate 80, the dosage of hexafluorobutyl methacrylate is lower, the probability and risk that the drug generates an adverse reaction are reduced, and the clinical medication safety is improved.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to a kind of improve compound andrographis paniculata injection safety medicine
The preparation method of compositionss.
Background technology
Compound andrographis paniculata injection standard is recorded and is issued drug standard (Traditional Chinese medicine historical preparation) in Ministry of Public Health, and crude drug is punching
Lotus, Rhizoma Coptidis, Radix Isatidis, 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 andrographis paniculata 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 andrographis paniculata 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 preparation method of CHUANXINLIAN ZHUSHEYE safety.
The present invention solves above-mentioned technical problem and be employed technical scheme comprise that：A kind of raising compound andrographis paniculata injection safety
The pharmaceutical composition of property, mainly by Herba Andrographis extract, Rhizoma Coptidis extract, Radix Isatidis 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 andrographis paniculata injection safety pharmaceutical composition, comprises the steps：
(1) compound andrographis paniculata injection raw medicinal material Herba Andrographis 100g, Rhizoma Coptidis 100g, Radix Isatidis 100g, cosolvent 2.0g；
(2) Herba Andrographis, Rhizoma Coptidis 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 Isatidis 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 andrographis paniculata 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 andrographis paniculata injection occurs untoward reaction in clinical practice, improve clinical application
Safety.
To sum up, the invention has the beneficial effects as follows：There is provided 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 andrographis paniculata injection；Poly- second two
Alcohol (PEG) 12-hydroxy stearic acid ester (Solutol) safety is higher than polyoxyethylene sorbitan monoleate (Tween 80) and also consumption
Lower, reduce probability and the risk that medicine occurs untoward reaction, improve the safety of clinical application.
Specific embodiment
Embodiment 1
Preparation method：Herba Andrographis, Rhizoma Coptidis 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 Isatidis 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 1000ml solution.Stir evenly.With 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.By above-mentioned solution through micropore
Filter membrane filters.Fill, sterilizing, obtain final product.
Embodiment 2
Preparation method：Herba Andrographis, Rhizoma Coptidis 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 Isatidis 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 note with tween 80
Penetrate and be configured to 1000ml solution with water.Stir evenly.With 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.Will be above-mentioned molten
Liquid filters through microporous filter membrane.Fill, sterilizing, obtain final product.
Embodiment 3
Preparation method：Herba Andrographis, Rhizoma Coptidis 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 Isatidis 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 Herba Andrographis extract of the present invention, Rhizoma Coptidis extract, Radix Isatidis 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 andrographis paniculata injection raw medicinal material Herba Andrographis 100g, Rhizoma Coptidis 100g, Radix Isatidis 100g, Polyethylene Glycol
(PEG) 12-hydroxy stearic acid ester (Solutol)2.0g；
(2) Herba Andrographis, Rhizoma Coptidis 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 Isatidis 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 preparation method improving compound andrographis paniculata injection safety pharmaceutical composition, comprises the steps：
(1) compound andrographis paniculata injection raw medicinal material Herba Andrographis 100g, Rhizoma Coptidis 100g, Radix Isatidis 100g, cosolvent 2.0g；
(2) Herba Andrographis, Rhizoma Coptidis add water to cook secondary, 2 hours every time, collecting decoction, plus ethanol filtering and concentrating, plus 3 times amount water, fill
Divide stirring, cold preservation 48 hours, filtration, filtrate reduced in volume to relative density is about 1.15, and medicinal liquid is standby；
(3) Radix Isatidis add water to cook secondary, 1 hour every time, collecting decoction, filtration, concentrate filtrate, let cool, plus ethanol make containing second
Alcohol amount is 65%, stands overnight, filtration, and filtrate reduced in volume to relative density is 1.20, plus ethanol makes containing amount of alcohol to 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, filtration, filter
It is 1.15 that liquid is concentrated into relative density,
(4) merge with above-mentioned all medicinal liquids, plus 2 times amount water, be sufficiently stirred for, cold preservation 24 hours, filtration, filtrate add cosolvent and
Water for injection is configured to 1000ml solution, stirs 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.
2. a kind of preparation method improving compound andrographis paniculata injection safety pharmaceutical composition according to claim 1,
It is characterized in that, in described step (1), cosolvent is made up of with polyoxyethylene sorbitan monoleate Hexafluorobutyl mathacrylate, wherein methyl
The content of hexafluorobutyl acrylate is 0.005g～2.0g, balance of polyoxyethylene sorbitan monoleate.
3. a kind of preparation method improving compound andrographis paniculata injection safety pharmaceutical composition according to claim 1,
It is characterized in that, in described step (2), plus the process of ethanol filtering and concentrating is first to filter to get filtrate, and filtrate reduced in volume is to phase
It is 1.27～1.30 to density, lets cool, plus ethanol makes containing amount of alcohol to be 65%, stands overnight, filtration, decompression filtrate recycling ethanol
And it is concentrated into relative density for 1.30.
4. a kind of preparation method improving compound andrographis paniculata injection safety pharmaceutical composition according to claim 1,
It is characterized in that, in described step (3), it is 1.25～1.30 that filtrate is concentrated into relative density.
5. a kind of preparation method improving compound andrographis paniculata injection safety pharmaceutical composition according to claim 1,
It is characterized in that, in described step (5), the mass percent of the sodium hydroxide solution of use is 20%.
6. a kind of preparation method improving compound andrographis paniculata injection safety pharmaceutical composition according to claim 1,
It is characterized in that, in described step (6), solution uses filtering with microporous membrane.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344504A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Pharmaceutical composition capable of improving safety of compound andrographis injection |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104288436A (en) * | 2014-09-30 | 2015-01-21 | 天津瑞贝特科技发展有限公司 | Veterinary injection with effects of astringing intestine to stop diarrhea and preparation method of veterinary injection |
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2016
- 2016-11-06 CN CN201610968052.7A patent/CN106389319A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104288436A (en) * | 2014-09-30 | 2015-01-21 | 天津瑞贝特科技发展有限公司 | Veterinary injection with effects of astringing intestine to stop diarrhea and preparation method of veterinary injection |
Non-Patent Citations (1)
| Title |
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| 易红等: "几种注射用表面活性剂的质量标准及安全性概述", 《中国实验方剂学杂志》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344504A (en) * | 2016-11-06 | 2017-01-25 | 成都先先先生物科技有限公司 | Pharmaceutical composition capable of improving safety of compound andrographis injection |
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