CN1290491C - Medicine for treating acute ischemic cerebral apoplexy and its preparing method - Google Patents
Medicine for treating acute ischemic cerebral apoplexy and its preparing method Download PDFInfo
- Publication number
- CN1290491C CN1290491C CN 200410012533 CN200410012533A CN1290491C CN 1290491 C CN1290491 C CN 1290491C CN 200410012533 CN200410012533 CN 200410012533 CN 200410012533 A CN200410012533 A CN 200410012533A CN 1290491 C CN1290491 C CN 1290491C
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- Prior art keywords
- butyphthalide
- excipient
- emulsifying agent
- injection
- medicine
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- Expired - Lifetime
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- 239000003814 drug Substances 0.000 title claims abstract description 15
- 208000006011 Stroke Diseases 0.000 title claims abstract description 13
- 206010008190 Cerebrovascular accident Diseases 0.000 title claims description 12
- 230000001154 acute effect Effects 0.000 title claims description 10
- 230000002490 cerebral effect Effects 0.000 title claims description 10
- 230000000302 ischemic effect Effects 0.000 title claims description 9
- 238000000034 method Methods 0.000 title description 4
- 229940079593 drug Drugs 0.000 title description 2
- 238000002347 injection Methods 0.000 claims abstract description 21
- 239000007924 injection Substances 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 15
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims abstract description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 238000005262 decarbonization Methods 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 239000008215 water for injection Substances 0.000 claims description 13
- HJXMNVQARNZTEE-UHFFFAOYSA-N Butylphthalide Chemical compound C1=CC=C2C(CCCC)OC(=O)C2=C1 HJXMNVQARNZTEE-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 239000007957 coemulsifier Substances 0.000 claims description 9
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- 239000000843 powder Substances 0.000 claims description 8
- 229950005197 butylphthalide Drugs 0.000 claims description 7
- 238000012856 packing Methods 0.000 claims description 7
- ZPIKVDODKLJKIN-NSHDSACASA-N Senkyunolide Chemical compound C1CC=CC2=C1[C@H](CCCC)OC2=O ZPIKVDODKLJKIN-NSHDSACASA-N 0.000 claims description 6
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 239000008347 soybean phospholipid Substances 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 239000003610 charcoal Substances 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000000787 lecithin Substances 0.000 claims description 3
- 235000010445 lecithin Nutrition 0.000 claims description 3
- 229940067606 lecithin Drugs 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- 108010009736 Protein Hydrolysates Proteins 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 230000006340 racemization Effects 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 5
- 229920001993 poloxamer 188 Polymers 0.000 claims 1
- 238000004108 freeze drying Methods 0.000 abstract description 7
- OCKPCBLVNKHBMX-UHFFFAOYSA-N butylbenzene Chemical compound CCCCC1=CC=CC=C1 OCKPCBLVNKHBMX-UHFFFAOYSA-N 0.000 abstract 4
- 208000032382 Ischaemic stroke Diseases 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 206010008118 cerebral infarction Diseases 0.000 description 5
- 201000006474 Brain Ischemia Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000007901 soft capsule Substances 0.000 description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
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- 239000001387 apium graveolens Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
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- 231100000419 toxicity Toxicity 0.000 description 2
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- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010060840 Ischaemic cerebral infarction Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
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- 229920005549 butyl rubber Polymers 0.000 description 1
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- 239000007921 spray Substances 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a medicine for treating acute ischemic stroke and a preparation method thereof. The medicine is prepared from the raw materials of the weight ratio of 5 to 8 of butylbenzene phthalein, 1 to 5 of emulsifying agent, 0 to 1 of auxiliary emulsifying agent, 4 to 10 of excipient and 5 to 11 of injection water. The medicine has the preparation method that the component raw materials are weighed according to the weight ratio, and a part of injection water is added into the butylbenzene phthalein, the emulsifying agent and the auxiliary emulsifying agent and uniformly stirred at high speed; a part of injection water is additionally taken and used for dissolving the excipient, active carbon accounting for 0.1% of the total weight is added to decarbonize the excipient after the excipient is heated for 15 minutes at 100 DEGC; after two solutions are mixed, the active carbon of 0.01% of the total weight is added for filtration and decarbonization; the injection water is additionally added to total amount; the pH value and the content are measured; physic liquor is separately bottled, frozen and dried to obtain freeze-drying injection solution after the physic liquor is finely filtered. The present invention provides an emergent instillation medicine for rescuing serious stroke patients to satisfy clinic emergency.
Description
Technical field
The present invention relates to pharmaceutical preparation, relate to a kind of medicament for the treatment of acute ischemic cerebral apoplexy and preparation method thereof specifically.
Background technology
The chemistry of butyphthalide is called dl-3-normal-butyl Phthalide.Butyphthalide is the levo form that extracts from celery seed, after synthetic is a raceme.Butyphthalide has the drug action of anti-cerebral ischemia.The oral formulations one butyphthalide soft capsule listing of at present existing butyphthalide.The indication of butyphthalide soft capsule is the treatment acute ischemic cerebral apoplexy.Apoplexy is that its final result is a cerebral infarction because the blood flow minimizing of a certain particular blood vessel of supply brain continues to cause nervous system disease more than 24 hours.The sickness rate of apoplexy, mortality rate, disability rate are all very high, cause very big burden for family and society, along with the aging of China's population and the increase of hypertension prevalence, patients with cerebral apoplexy also increases to some extent, but the butyphthalide soft capsule also is not suitable for the cerebral apoplexy patient use, its onset is slow, more is unfavorable for rescuing the critical patient.Because butyphthalide is an oily liquids, poorly water-soluble is not seen with injection medicament as yet so be directly used in rescue the clinical of critical patient so far again.
Summary of the invention
The purpose of this invention is to provide a kind of injection butyphthalide medicament, satisfying clinical requirement to different dosage form, thus can the intravenous drip administration, be used for the first aid of acute ischemic cerebral apoplexy, some critical patients can in time be rescued, for the quality time is won in next step treatment.
Medicament of the present invention is made by active component butyphthalide, emulsifying agent and co-emulsifier, excipient and water for injection, and its raw material weight ratio is butyphthalide 4-9; Emulsifying agent 1-4; Co-emulsifier 0-1; Excipient is 4-10; Water for injection is 5-11.Because butyphthalide is flaxen clear and bright oily liquids, poorly water-soluble, at first must solve its water-insoluble, thereby add emulsifying agent and co-emulsifier, with Fluko FM300 type dispersion emulsifying machine, under high-speed stirred, form transparent and homogeneous solution, under ultramicroscope, observe, decentralized photo spherolite granularity more than 80% is arranged below 1.0 μ m, or particle diameter is littler, to meet quiet notes administration requirement.Injection butyphthalide manufacturing process adopts freeze-drying, and medicine becomes solid in sharp freezing after making medicinal liquid, removes under vacuum and the low temperature moisture being distilled under the frozen state again, makes lyophilized injectable powder.
In order in freeze-drying process, to help medicinal liquid lyophilizing molding, add excipient, play the support frame effect, make the dried frozen aquatic products crystallization even simultaneously, certain dissolubility and physical strength are arranged.
The active component butyphthalide comprises racemization butyphthalide, the levo butyl phthalide of synthetic and has the Butylphthalide from the celery seed separation and Extraction, the Senkyunolide A of butyphthalide pharmacologically active in the prescription.
The emulsifying agent that the injection butyphthalide uses comprises but is not limited to soybean phospholipid, poloxamer (pluronicF-68), lecithin, co-emulsifier includes but not limited to ethanol, propylene glycol, and excipient includes but not limited to mannitol, glucose, lactose, sucrose, gelatin hydrolysate, glycine, sodium chloride.Excipient can be selected a kind of or wherein two kinds of uses together.
The technology of injection butyphthalide is packing operation and freeze-drying process, and the packing operation comprises dosing-filtration-fill, and freeze-drying process comprises pre-freeze-sublimation drying-heat preservation and dryness.Concrete operations are as follows:
System packing medicinal liquid:
1, by each component of proportioning weighing;
2, a butyphthalide and emulsifying agent and co-emulsifier-adding part water for injection high-speed stirred is even, to clear solution, and no oil droplet;
3, get part water for injection excipient dissolving in addition, add the 100 ℃ of heating of active carbon that account for gross weight 0.1% and take off charcoal after 15 minutes;
4, (2) add the active carbon of gross weight 0.01% with after (3) solution mixes, filtering decarbonization, and benefit adds to the full amount of water for injection, and surveys pH value, content, behind the fine straining, in the sub-bottling.
The system lyophilized injection:
1, the bottle of packing medicinal liquid is put in the freeze dryer, temperature is reduced to-40 ℃ by 10 ℃ after 40 minutes, and pre-freeze freezed sample in 3 hours fully.
2, open condensation with refrigeration, when temperature reaches-45 ℃, open vacuum, after 3 minutes, open butterfly valve, the case tube communicates.
3, during at 10～30Pa, the heating of beginning shelf heats up drying baker gradually at pressure, keeps 4 hours after rising to 25 ℃, closes valve between freeze drying box and the condenser, and freeze drying box is in 30～60 seconds, and pressure rises and is no more than 3～8Pa, the dry end.
4, sealing of lid butyl rubber plug and plastic-aluminum combined lid and packing.
5, product examination: the outward appearance slightly faint yellow loose block that is white in color, there is not a spray bottle phenomenon, goods do not have the atrophy phenomenon, are dissolved into clear and bright solution rapidly after adding solvent, and sample send chemical examination.
The inventor has carried out the research of content, character, discriminating, acidity, moisture, related substance, pyrogen, aseptic, content uniformity, clarity, assay to this medicament.Content: three batch samples after measured, labelled amount is 90.0%～110.0%, so determine that this product contains butyphthalide (C as a result
12H
14O
2) should be 90.0%～110.0% of labelled amount.Character: be " the slightly faint yellow loose block of white ".Acidity: pH value is 4.5～6.5.Moisture: do not surpass 2.0%.
Test 10 days results of investigation through the influence factor and show that every index is all stable; This product is investigated 6 months results through accelerated test and is shown, every index is all stable, with this product shading, airtight, preserves at shady and cool dry place, can preserve 2 years; This product is investigated 12 months through long term test, and every index all meets quality standard.
The drug effect of butyphthalide, existing both at home and abroad a large amount of reports, pharmacological evaluation shows; butyphthalide can improve the global brain ischemia energy metabolism and exhaust; dwindle the cerebral infarct size that local cerebral ischemia causes; improve function of nervous system, improve cerebral blood flow and brain microcirculation, alleviate dysmnesia and cerebral edema that local cerebral ischemia causes.Curative effect and the safety of butyphthalide in the acute ischemic cerebrovascular disease early treatment after deliberation confirms that butyphthalide treatment acute ischemic cerebral infarction has tangible curative effect and safety.Lyophilized injectable powder drug effect of the present invention is identical with soft capsule.
Make local application's toxicity research:
1, blood vessel irritation test
Injection is after 3 days continuously for rabbit, and the injection site Non Apparent Abnormality takes place, and the blood vessel surrounding tissue is not also found obviously phenomenons such as redness, hyperemia, with the negative control no significant difference.Pathologic finding does not have obvious pathological changes.
2, hemolytic test
The injection butyphthalide does not have obvious haemolysis, but injection for intravenous is used.
3, hypersensitive test
The injection butyphthalide does not have irritated effect to Cavia porcellus, and anaphylaxis is negative.
Injection butyphthalide lyophilized injectable powder, its formulation and technology is rationally feasible, and steady quality is reliable, and drug effect is definite, and local application's toxicity research shows that clinical drug safety is reliable.Be mainly used in acute ischemic cerebral apoplexy.
The specific embodiment
1000 bottles of butyphthalide lyophilized injectable powders of embodiment 1 preparation
Composition of raw materials: butyphthalide 200g
Soybean phospholipid (injection stage) 80g
Mannitol 200g
Water for injection adds to 4000ml
Preparation technology:
1, takes by weighing butyphthalide, soybean phospholipid and mannitol respectively by recipe quantity.
2, to add 2000ml water for injection high-speed stirred with soybean phospholipid even for butyphthalide, to clear solution, and no oil droplet.
3, after mannitol added the dissolving of 1500ml water for injection, the 100 ℃ of heating of active carbon that add gross weight 0.1% were taken off charcoal after 15 minutes.
4, (2) with after (3) solution mixes, after the active carbon that adds gross weight 0.01% stirs, and filtering decarbonization, benefit adds to the full amount of water for injection, and surveys pH value, content, behind the fine straining, in the sub-bottling.
5, the bottle of packing medicinal liquid is put in the freeze dryer, lyophilizing promptly.
Embodiment 2, and butyphthalide or levo butyl phthalide 300 grams are revolved in cancellation, lecithin 100 grams, and ethanol 50 grams, gelatin hydrolysate 150 grams, lactose 100 grams, 3000 milliliters of waters for injection prepare the butyphthalide lyophilized injectable powder with reference to embodiment 1 preparation technology.
Embodiment 3, get Butylphthalide or Senkyunolide A 250 grams, poloxamer (piuronic F-68) 100 grams, and propylene glycol 50 grams, glucose 200 grams, 4500 milliliters of waters for injection prepare the butyphthalide lyophilized injectable powder with reference to embodiment 1 preparation technology.
Claims (2)
1, a kind of medicament for the treatment of acute ischemic cerebral apoplexy, it is characterized in that it being the lyophilized injectable powder of being made by active ingredient butyphthalide, emulsifying agent and co-emulsifier, excipient and water for injection, each raw material weight ratio is: active ingredient butyphthalide: emulsifying agent: co-emulsifier: excipient: water for injection=4-9: 1-4: 0-1: 4-10: 5-11; Racemization butyphthalide that said active ingredient butyphthalide is a synthetic or levo butyl phthalide or Butylphthalide or Senkyunolide A; Said emulsifying agent is soybean phospholipid or lecithin, or poloxamer pluronic F-68; Said co-emulsifier is ethanol or propylene glycol; Said excipient be one of mannitol, glucose, lactose, sucrose, gelatin hydrolysate, glycine, sodium chloride or two.
2, according to the medicaments preparation method of the described treatment acute ischemic cerebral apoplexy of claim 1, it is characterized in that:
A, take by weighing active ingredient butyphthalide and emulsifying agent, co-emulsifier and excipient respectively;
B, active ingredient and emulsifying agent, co-emulsifier add part water for injection, and high-speed stirred is even, to clear solution, and no oil droplet;
C, excipient add and add the 100 ℃ of heating of active carbon that account for total amount 0.1% after the injection water dissolving and take off charcoal after 15 minutes;
D, b and c made solution and mix after, add account for total amount 0.01% active carbon and stir after, filtering decarbonization, benefit adds to the full amount of water for injection, and surveys pH value, content, behind the fine straining, in the sub-bottling;
E, with the packing medicinal liquid the bottle put in the freeze dryer, lyophilizing promptly gets the butyphthalide lyophilized injectable powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410012533 CN1290491C (en) | 2004-09-20 | 2004-09-20 | Medicine for treating acute ischemic cerebral apoplexy and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410012533 CN1290491C (en) | 2004-09-20 | 2004-09-20 | Medicine for treating acute ischemic cerebral apoplexy and its preparing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1615938A CN1615938A (en) | 2005-05-18 |
| CN1290491C true CN1290491C (en) | 2006-12-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200410012533 Expired - Lifetime CN1290491C (en) | 2004-09-20 | 2004-09-20 | Medicine for treating acute ischemic cerebral apoplexy and its preparing method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109985035A (en) * | 2017-12-29 | 2019-07-09 | 石药集团恩必普药业有限公司 | Pharmaceutical product containing butylphthalide preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100367951C (en) | 2005-12-16 | 2008-02-13 | 石药集团恩必普药业有限公司 | Butylphthalide Intravenous Emulsion and Its Application |
| CN100471494C (en) * | 2005-12-24 | 2009-03-25 | 石药集团中奇制药技术（石家庄）有限公司 | Butylphthalide dripping pills and preparation method |
| CN103505409B (en) * | 2012-06-27 | 2017-12-26 | 石药集团中奇制药技术（石家庄）有限公司 | A kind of butylphthalide injection and preparation method thereof |
| CN104721166A (en) * | 2013-12-21 | 2015-06-24 | 石药集团恩必普药业有限公司 | Butylphthalide liquid hard capsule preparation and preparation method thereof |
| CN109419800B (en) * | 2017-08-30 | 2021-04-30 | 石药集团恩必普药业有限公司 | Pharmaceutical composition and application thereof |
| CN110856712B (en) * | 2018-08-06 | 2021-11-30 | 刘超 | Butylphthalide self-microemulsion composition, preparation method and application thereof |
| CN109528709A (en) * | 2018-12-03 | 2019-03-29 | 新乡医学院 | Application of butylphthalide in the protection of intracerebral hippocampal gamma network oscillations induced by acute alcoholism |
| CN116407510B (en) * | 2021-12-29 | 2025-11-21 | 河北赛谱睿思医药科技有限公司 | Sublingual tablet of butylphthalide and preparation method thereof |
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2004
- 2004-09-20 CN CN 200410012533 patent/CN1290491C/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109985035A (en) * | 2017-12-29 | 2019-07-09 | 石药集团恩必普药业有限公司 | Pharmaceutical product containing butylphthalide preparation |
| CN109985035B (en) * | 2017-12-29 | 2023-02-07 | 石药集团恩必普药业有限公司 | A pharmaceutical product comprising a butylphthalide preparation |
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| CN1615938A (en) | 2005-05-18 |
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