CN106309904A - Preparation method for medicine compound for increasing safety of compound schisandra chinensis injection - Google Patents
Preparation method for medicine compound for increasing safety of compound schisandra chinensis injection Download PDFInfo
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- CN106309904A CN106309904A CN201610968040.4A CN201610968040A CN106309904A CN 106309904 A CN106309904 A CN 106309904A CN 201610968040 A CN201610968040 A CN 201610968040A CN 106309904 A CN106309904 A CN 106309904A
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- 238000002347 injection Methods 0.000 title claims abstract description 39
- 239000007924 injection Substances 0.000 title claims abstract description 39
- 150000001875 compounds Chemical class 0.000 title claims abstract description 27
- 240000006079 Schisandra chinensis Species 0.000 title claims abstract description 23
- 235000008422 Schisandra chinensis Nutrition 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000003814 drug Substances 0.000 title abstract description 22
- 239000006184 cosolvent Substances 0.000 claims abstract description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 76
- 239000000706 filtrate Substances 0.000 claims description 48
- 239000000243 solution Substances 0.000 claims description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 239000007788 liquid Substances 0.000 claims description 23
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 22
- 238000004321 preservation Methods 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 15
- 239000009636 Huang Qi Substances 0.000 claims description 12
- 238000009835 boiling Methods 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 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
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000004064 recycling Methods 0.000 claims description 2
- 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
- 230000000694 effects Effects 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 6
- 239000000284 extract Substances 0.000 abstract description 6
- XPJVKCRENWUEJH-UHFFFAOYSA-N Isobutylparaben Chemical compound CC(C)COC(=O)C1=CC=C(O)C=C1 XPJVKCRENWUEJH-UHFFFAOYSA-N 0.000 abstract 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 abstract 2
- 229940068968 polysorbate 80 Drugs 0.000 abstract 2
- 235000019206 astragalus extract Nutrition 0.000 abstract 1
- 239000002202 Polyethylene glycol Substances 0.000 description 25
- 229920001223 polyethylene glycol Polymers 0.000 description 25
- -1 12-hydroxy stearic acid ester Chemical class 0.000 description 11
- 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
- 239000012528 membrane Substances 0.000 description 5
- 239000000203 mixture 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
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 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
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 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
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 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
- 238000007670 refining Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
Classifications
-
- 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)
- A61K36/79—Schisandraceae (Schisandra 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- 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)
- A61K36/57—Magnoliaceae (Magnolia 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8968—Ophiopogon (Lilyturf)
-
- 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
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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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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- 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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- 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
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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
- A61K2236/50—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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- 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
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method for a medicine compound for increasing the safety of a compound schisandra chinensis injection. The medicine compound is an injection medicine compound which is made from schisandra chinensis extract, radix ophiopogonis extract, astragalus extract and isobutyl 4-hydroxybenzoate. According to the invention, a cosolvent with higher safety and more obvious fluxing effect is used for replacing the cosolvent polysorbate 80 with potential safety hazards and influences on product quality in the compound schisandra chinensis injection, the safety of isobutyl 4-hydroxybenzoate is higher than the safety of polysorbate 80 and the dosage is less, so that the probability and risk of untoward effects of the medicine can be reduced and the safety of clinical medication can be increased.
Description
Technical field
The invention belongs to pharmaceutical technology field, improve Schisandra chinensis compound injection safety medicine in particular it relates to a kind of
The preparation method of compositions.
Background technology
Schisandra chinensis compound injection standard is recorded in health drug standard promulgated by the ministries or commissions of the Central Government (Traditional Chinese medicine historical preparation), and crude drug is the five tastes
Son, Radix Ophiopogonis, the Radix Astragali, 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 Schisandra chinensis compound injection
Comment.But in recent years, the Reporting of harms of Chinese medicine injection clinical practice is on the rise, and have impact on and has 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, and it is reported by document
The generation of untoward reaction has very with the cosolvent polyoxyethylene sorbitan monoleate (Tween 80) of the existence potential safety hazard of addition in Chinese medicine injection
Big relation.Due to Chinese medicine injection complicated component, in storage and autoclaving process, easily occur that solute separates out and affects clear
The problems such as lightness, solution ph are decreased obviously, therefore add polyoxyethylene sorbitan monoleate (Tween 80) in such injection and make hydrotropy
Agent, the solubilization-aid effect adding other cosolvents is the most inconspicuous.But polyoxyethylene sorbitan monoleate (Tween 80) is immature due to process for refining,
Storage and autoclaving process are easily become sour, causes impurity content high, it is difficult to reaching injection standard, polyoxyethylene sorbitan monoleate (is told
Temperature 80) inherently there is stronger hemolytic and anaphylaxis, apply add in injection occur untoward reaction probability and
Risk.It addition, Chinese medicine injection there is also, in sterilizing and storage process itself, the problem that solution ph is decreased obviously, and poly-Pyrusussuriensis
Ester 80 (Tween 80) the most easily becomes sour, and more accelerates the decline of the pH value of medicinal liquid.The Schisandra chinensis compound injection of domestic production at present
Liquid also adds polyoxyethylene sorbitan monoleate (Tween 80) and makees cosolvent, be faced with same problem.
In view of the foregoing, the poly-mountain that safety is more preferable, poor stability replaced by the more obvious cosolvent of solubilization-aid effect is found
Pear ester 80 (Tween 80) is this injection urgent problem.
Summary 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 preparation method of the pharmaceutical composition of Fructus Schisandrae Chinensis injection safety.
The present invention solves above-mentioned technical problem and be the technical scheme is that a kind of raising Schisandra chinensis compound injection safety
The pharmaceutical composition of property, the confession being mainly made up of Fructus Schisandrae Chinensis extrat, Radix Ophiopogonis extract, Radix Astragali extract and iso-butyl p-hy-droxybenzoate
Medicinal composition for injections.
Specifically, the consumption of iso-butyl p-hy-droxybenzoate is 0.005g～5.0g/100ml；The consumption of iso-butyl p-hy-droxybenzoate is preferred
For 0.05g～1.0g/100ml.
Aforementioned pharmaceutical compositions also including, polyoxyethylene sorbitan monoleate, iso-butyl p-hy-droxybenzoate and polyoxyethylene sorbitan monoleate press different proportion connection
Cooperation cosolvent, the usage ratio of iso-butyl p-hy-droxybenzoate and polyoxyethylene sorbitan monoleate be 0.005g～5.0g/100ml:0.001g～
2.0g/100ml。
Described medicine composition dosage form is injection, powder pin or lyophilizing.
A kind of preparation method improving Schisandra chinensis compound injection safety pharmaceutical composition, comprises the steps:
(1) Schisandra chinensis compound injection raw medicinal material Fructus Schisandrae Chinensis 100g, 100g Radix Ophiopogonis, Radix Astragali 100g, cosolvent 2.0g；
(2) Fructus Schisandrae Chinensis, boiling Radix Ophiopogonis secondary, each 2 hours, collecting decoction, add ethanol filtering and concentrating, add 3 times amount
Water, is sufficiently stirred for, cold preservation 48 hours, filters, and filtrate reduced in volume to relative density is about 1.15, and medicinal liquid is standby；
(3) Radix Astragali boiling secondary, each 1 hour, collecting decoction, filter, concentrated filtrate, let cool, add ethanol and make to contain
Amount of alcohol is 65%, stands overnight, and filters, and filtrate reduced in volume to relative density is 1.20, adds ethanol and makes and containing amount of alcohol is
70%, stand overnight, filter, it is 1.30 that filtrate is concentrated into relative density, adds 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filter
Crossing, it is 1.15 that filtrate is concentrated into relative density,
(4) merge with above-mentioned all medicinal liquids, add 2 times amount water, be sufficiently stirred for, cold preservation 24 hours, filter, 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) by sodium hydroxide solution regulation solution ph to 6.5-8.5；
(6) filter, fill, sterilizing, to obtain final product.
For the method that the present invention is better achieved, further, in described step (1), cosolvent is by nipalgin isobutyl
Ester forms with polyoxyethylene sorbitan monoleate, and wherein the content of iso-butyl p-hy-droxybenzoate is 0.005g～2.0g, and surplus is polyoxyethylene sorbitan monoleate.
For the method that the present invention is better achieved, further, in described step (2), the mistake of ethanol filtering and concentrating is added
Cheng Wei, first filters to get filtrate, and filtrate reduced in volume to relative density is 1.27～1.30, lets cool, and adds ethanol and makes and containing amount of alcohol is
65%, stand overnight, filter, decompression filtrate recycling ethanol to be concentrated into relative density be 1.30.
For the method that the present invention is better achieved, further, in described step (3), filtrate is concentrated into relative density
It is 1.25～1.30.
For the method that the present invention is better achieved, further, in described step (5), the sodium hydroxide solution of use
Mass percent be 20%.
For the method that 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 Arzneibucs and British Pharmacopoeia, can be used for ejection preparation
Solubilizing agent.The pharmacological toxicology experimental data of document report shows that its toxicity is significantly lower than polyoxyethylene sorbitan monoleate (Tween 80).Additionally I
Be experimental studies have found that by substantial amounts of, reach Polyethylene Glycol (PEG) 12-hydroxy stearic acid ester during 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).(0.5g/100ml) Polyethylene Glycol (PEG) ten dihydroxy using equivalent in Schisandra chinensis compound injection respectively are hard
Fat acid ester (Solutol) and polyoxyethylene sorbitan monoleate (Tween 80), safety experiment comparative study result shows, uses
(0.5g/100ml) Polyethylene Glycol (PEG) 12-hydroxy stearic acid ester (Solutol of equivalent) group hemolytic,
Zest, anaphylaxis and the toxicity aspect the most substantially ratio such as reduce blood pressure use polyoxyethylene sorbitan monoleate (Tween 80) to organize low, pass through
The present invention considerably reduces Schisandra chinensis compound injection and probability and the risk of untoward reaction occurs in clinical practice, improves clinic
The safety of medication.
To sum up, the invention has the beneficial effects as follows: a kind of safety of offer is more preferable, the more obvious cosolvent of solubilization-aid effect is replaced
Schisandra chinensis compound injection exists potential safety hazard and affects the cosolvent polyoxyethylene sorbitan monoleate (Tween 80) of product quality；Poly-second two
Alcohol (PEG) 12-hydroxy stearic acid ester (Solutol) safety higher than polyoxyethylene sorbitan monoleate (Tween 80) and use
Measure lower, reduce probability and the risk of medicine generation untoward reaction, improve the safety of clinical application.
Detailed description of the invention
Embodiment 1
Preparation method: Fructus Schisandrae Chinensis, boiling Radix Ophiopogonis secondary, each 2 hours, collecting decoction, filter, filtrate reduced in volume
Being 1.27～1.30 (80 DEG C) to relative density, let cool, add ethanol and make containing amount of alcohol to be 65%, stand overnight, filtering, filtrate subtracts
Push back receipts ethanol and to be concentrated into relative density be 1.30 (80 DEG C), add 3 times amount water, be sufficiently stirred for, cold preservation 48 hours, filter, filter
Liquid is evaporated to relative density and is about 1.15 (80 DEG C), and medicinal liquid is standby；Radix Astragali boiling secondary, each 1 hour, merges and decocts
Liquid, filters, and it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, and adds ethanol and makes containing amount of alcohol to be 65%, stands
Overnight, filtering, filtrate reduced in volume to relative density is 1.20 (80 DEG C), adds ethanol and makes containing amount of alcohol to be 70%, stands overnight,
Filtering, it is 1.30 (80 DEG C) that filtrate is concentrated into relative density, adds 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filters, and filtrate is dense
Being reduced to relative density is 1.15 (80 DEG C), merges with above-mentioned medicinal liquid, adds 2 times amount water, be sufficiently stirred for, cold preservation 24 hours, filters, filter
Liquid adds Polyethylene Glycol (PEG) 12-hydroxy stearic acid ester (Solutol) make cosolvent and water for injection is configured to
1000ml solution.Stir evenly.By 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.By above-mentioned solution through microporous filter membrane
Filter.Fill, sterilizing, to obtain final product.
Embodiment 2
Preparation method: Fructus Schisandrae Chinensis, boiling Radix Ophiopogonis secondary, each 2 hours, collecting decoction, filter, filtrate reduced in volume
Being 1.27～1.30 (80 DEG C) to relative density, let cool, add ethanol and make containing amount of alcohol to be 65%, stand overnight, filtering, filtrate subtracts
Push back receipts ethanol and to be concentrated into relative density be 1.30 (80 DEG C), add 3 times amount water, be sufficiently stirred for, cold preservation 48 hours, filter, filter
Liquid is evaporated to relative density and is about 1.15 (80 DEG C), and medicinal liquid is standby；Radix Astragali boiling secondary, each 1 hour, merges and decocts
Liquid, filters, and it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, and adds ethanol and makes containing amount of alcohol to be 65%, stands
Overnight, filtering, filtrate reduced in volume to relative density is 1.20 (80 DEG C), adds ethanol and makes containing amount of alcohol to be 70%, stands overnight,
Filtering, it is 1.30 (80 DEG C) that filtrate is concentrated into relative density, adds 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filters, and filtrate is dense
Being reduced to relative density is 1.15 (80 DEG C), merges with above-mentioned medicinal liquid, adds 2 times amount water, be sufficiently stirred for, cold preservation 24 hours, filters, filter
Liquid adds Polyethylene Glycol (PEG) 12-hydroxy stearic acid ester (Solutol) make cosolvent and injection with tween 80
It is configured to 1000ml solution with water.Stir evenly.By 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.By above-mentioned solution
Filter through microporous filter membrane.Fill, sterilizing, to obtain final product.
Embodiment 3
Preparation method: Fructus Schisandrae Chinensis, boiling Radix Ophiopogonis secondary, each 2 hours, collecting decoction, filter, filtrate reduced in volume
Being 1.27～1.30 (80 DEG C) to relative density, let cool, add ethanol and make containing amount of alcohol to be 65%, stand overnight, filtering, filtrate subtracts
Push back receipts ethanol and to be concentrated into relative density be 1.30 (80 DEG C), add 3 times amount water, be sufficiently stirred for, cold preservation 48 hours, filter, filter
Liquid is evaporated to relative density and is about 1.15 (80 DEG C), and medicinal liquid is standby；Radix Astragali boiling secondary, each 1 hour, merges and decocts
Liquid, filters, and it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, and adds ethanol and makes containing amount of alcohol to be 65%, stands
Overnight, filtering, filtrate reduced in volume to relative density is 1.20 (80 DEG C), adds ethanol and makes containing amount of alcohol to be 70%, stands overnight,
Filtering, it is 1.30 (80 DEG C) that filtrate is concentrated into relative density, adds 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filters, and filtrate is dense
Being reduced to relative density is 1.15 (80 DEG C), merges with above-mentioned medicinal liquid, adds 2 times amount water, be sufficiently stirred for, cold preservation 24 hours, filters, filter
Liquid adds Polyethylene Glycol (PEG) 12-hydroxy stearic acid ester (Solutol) make cosolvent and water for injection is configured to
Solution.Stir evenly.By 20% sodium hydroxide solution regulation solution ph to 6.5-8.5.Above-mentioned solution is filtered through microporous filter membrane.Point
Dress up 1000, lyophilization, to obtain final product.
Embodiment 4:
The Fructus Schisandrae Chinensis extrat of the present invention, Radix Ophiopogonis extract, Radix Astragali extract and Polyethylene Glycol (PEG) ten dihydroxy are stearic
Acid esters (Solutol) the injection pharmaceutical composition made can be achieved through the following technical solutions:
(1) Schisandra chinensis compound injection raw medicinal material Fructus Schisandrae Chinensis 100g, 100g Radix Ophiopogonis, Radix Astragali 100g, Polyethylene Glycol (PEG)
12-hydroxy stearic acid ester (Solutol)2.0g；
(2) Fructus Schisandrae Chinensis, boiling Radix Ophiopogonis secondary, each 2 hours, collecting decoction, filter, filtrate reduced in volume is to relatively
Density is 1.27～1.30 (80 DEG C), lets cool, and adds ethanol and makes containing amount of alcohol to be 65%, stands overnight, and filters, and filtrate decompression reclaims
Ethanol to be concentrated into relative density be 1.30 (80 DEG C), adds 3 times amount water, is sufficiently stirred for, and cold preservation 48 hours filters, filtrate decompression
Being concentrated into relative density and be about 1.15 (80 DEG C), medicinal liquid is standby；Radix Astragali boiling secondary, each 1 hour, collecting decoction, filter
Crossing, it is 1.25～1.30 (80 DEG C) that filtrate is concentrated into relative density, lets cool, and adds ethanol and makes containing amount of alcohol to be 65%, stands overnight,
Filtering, filtrate reduced in volume to relative density is 1.20 (80 DEG C), adds ethanol and makes containing amount of alcohol to be 70%, stands overnight, and filters,
It is 1.30 (80 DEG C) that filtrate is concentrated into relative density, adds 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filters, and filtrate is concentrated into
Relative density is 1.15 (80 DEG C), merges with above-mentioned medicinal liquid, adds 2 times amount water, is sufficiently stirred for, cold preservation 24 hours, filters, and filtrate adds
Enter Polyethylene Glycol (PEG) 12-hydroxy stearic acid ester (Solutol) make cosolvent and water for injection is configured to
1000ml solution.Stir evenly.
(3) by 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, to obtain final product.
In the present invention, cosolvent can be iso-butyl p-hy-droxybenzoate, and its consumption is any in 0.005g～5.0g/100ml
Value, such as 0.005g/100ml, 0.01g/100ml, 0.05g/100ml, 1.0g/100ml, 5.0g/100ml etc.；Cosolvent also may be used
To be made up of with polyoxyethylene sorbitan monoleate iso-butyl p-hy-droxybenzoate, its usage ratio is 0.005g～5.0g/100ml:0.001g～2.0g/
100ml。
Claims (6)
1. improve a preparation method for Schisandra chinensis compound injection safety pharmaceutical composition, comprise the steps:
(1) Schisandra chinensis compound injection raw medicinal material Fructus Schisandrae Chinensis 100g, 100g Radix Ophiopogonis, Radix Astragali 100g, cosolvent 2.0g；
(2) Fructus Schisandrae Chinensis, boiling Radix Ophiopogonis secondary, each 2 hours, collecting decoction, add ethanol filtering and concentrating, add 3 times amount water, fill
Dividing stirring, cold preservation 48 hours, filter, filtrate reduced in volume to relative density is about 1.15, and medicinal liquid is standby；
(3) Radix Astragali boiling secondary, each 1 hour, collecting decoction, filter, concentrated filtrate, let cool, add ethanol and make containing ethanol
Amount is 65%, stands overnight, and filters, and filtrate reduced in volume to relative density is 1.20, adds ethanol and makes containing amount of alcohol to be 70%, quiet
Putting overnight, filter, it is 1.30 that filtrate is concentrated into relative density, adds 3 times amount water, is sufficiently stirred for, cold preservation 48 hours, filters, filtrate
Being concentrated into relative density is 1.15,
(4) merge with above-mentioned all medicinal liquids, add 2 times amount water, be sufficiently stirred for, cold preservation 24 hours, filter, 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) by sodium hydroxide solution regulation solution ph to 6.5-8.5；
(6) filter, fill, sterilizing, to obtain final product.
A kind of preparation method improving Schisandra chinensis compound injection safety pharmaceutical composition the most according to claim 1,
It is characterized in that, in described step (1), cosolvent is made up of with polyoxyethylene sorbitan monoleate iso-butyl p-hy-droxybenzoate, wherein nipalgin isobutyl
The content of ester is 0.005g～2.0g, and surplus is polyoxyethylene sorbitan monoleate.
A kind of preparation method improving Schisandra chinensis compound injection safety pharmaceutical composition the most according to claim 1,
It is characterized in that, in described step (2), the process adding 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, add ethanol and make containing amount of alcohol to be 65%, stand overnight, filter, decompression filtrate recycling ethanol
And to be concentrated into relative density be 1.30.
A kind of preparation method improving Schisandra chinensis compound injection safety pharmaceutical composition the most 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.
A kind of preparation method improving Schisandra chinensis compound injection safety pharmaceutical composition the most 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%.
A kind of preparation method improving Schisandra chinensis compound injection safety pharmaceutical composition the most according to claim 1,
It is characterized in that, in described step (6), solution uses filtering with microporous membrane.
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| CN1883654A (en) * | 2006-05-22 | 2006-12-27 | 海南康力元药业有限公司 | Pulse invigorating injection with astragalus root and preparation process thereof |
| CN1977918A (en) * | 2005-11-29 | 2007-06-13 | 天津宏仁堂药业有限公司 | Venous preparation and its preparing method |
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| CN101518617A (en) * | 2009-04-02 | 2009-09-02 | 四川升和制药有限公司 | Pharmaceutical composition for improving safety of Shenmai injection and method for preparing same |
| CN104887722A (en) * | 2015-05-06 | 2015-09-09 | 成都大学 | High-dissolvability high-safety ginkgo-damole injection and its preparation method and application |
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| CN1977918A (en) * | 2005-11-29 | 2007-06-13 | 天津宏仁堂药业有限公司 | Venous preparation and its preparing method |
| CN1981849A (en) * | 2005-12-16 | 2007-06-20 | 北京联合伟华药业有限公司 | Production and use for milkvetch root Shengmai injection |
| CN1883654A (en) * | 2006-05-22 | 2006-12-27 | 海南康力元药业有限公司 | Pulse invigorating injection with astragalus root and preparation process thereof |
| CN101491678A (en) * | 2009-02-25 | 2009-07-29 | 正大青春宝药业有限公司 | Preparation method of injector using tween-80 as solubilizer |
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| CN104887722A (en) * | 2015-05-06 | 2015-09-09 | 成都大学 | High-dissolvability high-safety ginkgo-damole injection and its preparation method and application |
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Application publication date: 20170111 |