US20060166931A1 - Clathrates of butylphtualide with cyclodextrin or its derivatives, a process for their preparation and the use thereof - Google Patents
Clathrates of butylphtualide with cyclodextrin or its derivatives, a process for their preparation and the use thereof Download PDFInfo
- Publication number
- US20060166931A1 US20060166931A1 US10/524,653 US52465305A US2006166931A1 US 20060166931 A1 US20060166931 A1 US 20060166931A1 US 52465305 A US52465305 A US 52465305A US 2006166931 A1 US2006166931 A1 US 2006166931A1
- Authority
- US
- United States
- Prior art keywords
- cyclodextrin
- butylphthalide
- inclusion complex
- derivatives
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- HJXMNVQARNZTEE-UHFFFAOYSA-N CCCCC1OC(=O)C2=CC=CC=C21 Chemical compound CCCCC1OC(=O)C2=CC=CC=C21 HJXMNVQARNZTEE-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
- C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
Definitions
- the present invention relates to pharmaceutical compositions. More particularly, it relates to the inclusion complexes of butylphthalide, which is D,L-mixed or levorotary, with cyclodextrin or its derivatives, to a process for their preparation and the use thereof.
- Butylphthalide is a water insoluble oily compound with the following formula:
- Butylphtualide can be obtained by extraction from natural celery seed oil or by chemical synthesis, as described in Chinese patent application No. 99109673.8 and the prior reference: Junshan Yang, Yalun Su, Chinese Pharmaceutical Bulletin, 1984, 31; 671, which realized the availability of butylphthalide.
- the pharmaceutical formulations are required to release active agents quickly and exert therapeutic effects rapidly when they are used to treat ischemia-induced diseases or thrombosis.
- the formulations for treating acute disease are administrated by intravenous instillation.
- the butylphthalide can only be formulated into soft capsules for oral administration because of its oily characteristics. Therefore, solubility problem of the butylphthalide must be resolved firstly in order to obtain injectable dosage forms.
- the present invention intends to provide inclusion complexes of butylphthalide with cyclodextrin or its derivatives, a process for their preparation and the use thereof.
- it is complexed with cyclodextrin or its derivatives, wherein the butylphthalide is D,L-mixed or levorotary, and the inclusion complexes may be used to prepare various clinically applicable solid and liquid formulations.
- An inclusion complex of butylphthalide with cyclodextrin or its derivatives comprises butylphthalide and cyclodextrin or its derivatives, wherein the molar ratio of butylphthalide to cyclodextrin or its derivatives is in the range of 1:1-10.
- the butylphthalide mentioned above comprises D,L-mixed or levorotatory butylphthalide.
- the cyclodextrin mentioned above is selected from the group consisting of ⁇ -cyclodextrin, ⁇ -cyclodextrin, and ⁇ -cyclodextrin.
- the derivatives of cyclodextrin mentioned above are selected from the group consisting of hydroxyethyl- ⁇ -cyclodextrin, hydroxypropyl- ⁇ -cyclodextrin, dihydroxypropyl- ⁇ -cyclodextrin, methyl- ⁇ -cyclodextrin, glucose cyclodextrin, maltose cyclodextrin, meltotriose cyclodextrin, carboxymethyl cyclodextrin, and sulfonylalkyl cyclodextrin.
- hydroxypropyl- ⁇ -cyclodextrin is preferred.
- a solution with a concentration of 5-60% is prepared by adding cyclodextrin or its derivatives into a suitable solvent vehicle.
- a liquid inclusion complex of butylphthalide with cyclodextrin or its derivatives is obtained by adding butylphthalide into the above solution, stirring to provide a clear and transparent solution without oil drops, wherein the molar ratio of butylphthalide to cyclodextrin or its derivatives is in the range of 1:1 to 1:10.
- the process mentioned above may further comprise drying the liquid inclusion complex of butylphthalide with cyclodextrin or its derivatives at the temperature of 40-80° C. to obtain a solid inclusion complex of butylphthalide with cyclodextrin or its derivatives.
- the process mentioned above may also comprise concentrating the liquid inclusion complex of butylphthalide with cyclodextrin or its derivatives until the concentration of cyclodextrin or its derivatives is 10-15% (W/V), cooling the solution for, e.g. about 12 hours to obtain white precipitate, filtering, and drying at 40-80° C., to obtain a solid inclusion complex of butylphthalide with cyclodextrin or its derivatives.
- a process for preparing the inclusion complex of butylphthalide with cyclodextrin or its derivatives comprises placing cyclodextrin or its derivatives into a colloid mill or mortar, adding an appropriate amount of suitable solvent vehicle, and stirring the mixture to provide a paste; adding butylphthalide into the paste described above, grinding for about 1-5 hours to provide a homogenous and viscous paste, then filtering the paste, and drying at 40-80° C. to obtain a solid inclusion complex of butylphthalide with cyclodextrin or its derivatives, wherein the molar ratio butylphthalide to cyclodextrin or its derivatives is in the range of 1:1-10.
- a process for preparing the inclusion complex of butylphthalide with cyclodextrin or its derivatives comprises adding cyclodextrin or its derivatives into a suitable solvent vehicle to obtain a solution with a concentration of 5-60%, dissolving the butylphthalide into an appropriate amount of ethanol with purity of 99%, mixing the two solutions, stirring, and drying to obtain a solid inclusion complex of butylphthalide with cyclodextrin or its derivatives, wherein the molar ratio butylphthalide to cyclodextrin or its derivatives is in the range of 1:1-10.
- the drying method mentioned above may be any drying method, such as direct drying, spray drying, or freeze-drying.
- solvent vehicles examples include water, ethanol, methanol, propanol, isopropanol, ethylene glycol, propylene glycol, glycerin, or acetone, or the mixture of any two or more above-mentioned solvent vehicles, wherein water is preferred.
- Such liquid inclusion complex of butylphthalide with cyclodextrin or its derivatives may be directly used to produce liquid formulations, such as infusion, injection, injectable powder, liquids for oral administration, syrup, and the like;
- the solid inclusion complex of butylphthalide with cyclodextrin or its derivatives may be used to produce solid formulations, such as tablets, capsules, granules, dispersible tablets, and the like.
- cyclodextrin or its derivatives could trap the butylphthalide into their tubular structure to generate an inclusion complex of butylphthalide with cyclodextrin or its derivatives, thereby improving the water-solubility of butylphthalide.
- the active ingredient butylphthalide in the form of inclusion complexes can be directly applied in solid or liquid dosage forms. Limitations such as poor water-solubility, disability to be directly applied in solid, especially injectable dosage forms can be overcome.
- Cyclodextrin or its derivatives are water-soluble pharmaceutical excipients with little toxicity.
- the inclusion complexes of butylphthalide with cyclodextrin or its derivatives prepared thereby are suitable to be formulated into various liquid and solid dosage forms.
- the inclusion complexes have the advantages such as good water-solubility and little vascular irritation.
- the solubility of inclusion complex of butylphthalide with hydroxypropyl-o-cyclodextrin in water at 25° C. is 924 mg/100 ml.
- the inclusion complex is particularly applicable for preparing liquid dosage forms.
- the present invention overcomes the limitation that butylphthalide cannot be used to prepare liquid formulations. Due to the fact that the water-solubility is improved, the resulting solid dosage forms have the advantages such as rapid disintegration, good solubility and high bioavailability, which is more applicable for clinical use.
- vascular irritation assay using inclusion complex of butylphthalide with hydroxypropyl- ⁇ -cyclodextrin is provided as follows:
- test group Eight rabbits were divided into two groups, namely, test group and control group.
- test group 2.45 g/kg of the inclusion complex together with 40 ml of 5% glucose were instilled via the marginal ear vein of a rabbit at the rate of 1.5 ml/min. The administration was once per day and lasted for 3 days.
- control group 10% acetic acid was administrated into the ear vein on one side and 5% glucose injection was instilled into the rabbit ear on the opposite side serving as negative control. The administration lasted for 3 days. Results showed that there was no topical abnormity in the test group after 3 days, similar to the negative control of 5% glucose injection. However, topical hyperaemia, thickening, and exudation were observed after 10% acetic acid injection.
- the assay suggests that instillation of the inclusion complex has little vascular irritation, and that the inclusion complex can be used to produce injectable dosage forms.
- hydroxypropyl- ⁇ -cyclodextrin is preferably used as trapping agent.
- suitable solvent vehicle for dissolving cyclodextrin or its derivatives is water.
- the inclusion complex is prepared by
- the solid inclusion complex is prepared by
- the solid inclusion complex is prepared by
- the lyophilized injectable powder is prepared by
- the saline infusion of the inclusion complex is prepared by
- the glucose infusion of the inclusion complex is prepared by
- the sterile injectable powder is prepared by
- the complexation process is conducted by
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Nanotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Polymers & Plastics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Biochemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Materials Engineering (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/200,130 US7678776B2 (en) | 2002-08-21 | 2008-08-28 | Inclusion complexes of butylphthalide with cyclodextrin or its derivatives, a process for their preparation and the use thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2002/000579 WO2004018444A1 (fr) | 2002-08-21 | 2002-08-21 | Clathrates de phtalide butylique associe a de la cyclodextrine ou a ses derives, procede de preparation desdites compositions et leur utilisation |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/200,130 Continuation US7678776B2 (en) | 2002-08-21 | 2008-08-28 | Inclusion complexes of butylphthalide with cyclodextrin or its derivatives, a process for their preparation and the use thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
US20060166931A1 true US20060166931A1 (en) | 2006-07-27 |
Family
ID=31892708
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/524,653 Abandoned US20060166931A1 (en) | 2002-08-21 | 2002-08-21 | Clathrates of butylphtualide with cyclodextrin or its derivatives, a process for their preparation and the use thereof |
US12/200,130 Expired - Lifetime US7678776B2 (en) | 2002-08-21 | 2008-08-28 | Inclusion complexes of butylphthalide with cyclodextrin or its derivatives, a process for their preparation and the use thereof |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/200,130 Expired - Lifetime US7678776B2 (en) | 2002-08-21 | 2008-08-28 | Inclusion complexes of butylphthalide with cyclodextrin or its derivatives, a process for their preparation and the use thereof |
Country Status (13)
Country | Link |
---|---|
US (2) | US20060166931A1 (ja) |
EP (1) | EP1535916B1 (ja) |
JP (1) | JP4378755B2 (ja) |
AT (1) | ATE489972T1 (ja) |
AU (1) | AU2002327307B8 (ja) |
BR (1) | BR0215848A (ja) |
CA (1) | CA2494157C (ja) |
DE (1) | DE60238510D1 (ja) |
DK (1) | DK1535916T3 (ja) |
ES (1) | ES2355133T3 (ja) |
HK (1) | HK1074200A1 (ja) |
NO (1) | NO20050629L (ja) |
WO (1) | WO2004018444A1 (ja) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070112065A1 (en) * | 2003-10-10 | 2007-05-17 | Shijiazhuang Pharma. Group Zhongqi Pharmaceutical | Use of l-butylphthalide in the manufacture of medicaments for prevention and treatment of cerebral infarct |
US20070134316A1 (en) * | 2003-12-05 | 2007-06-14 | Shijiazhuang Pharma. Group Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. | Soft capsule of butylphthalide and a process for preparing the same |
US10463614B2 (en) | 2005-12-16 | 2019-11-05 | Shijiazhuang Pharma Group Nbp Pharmaceutical Co. | Butylphthalide intravenous emulsion and application thereof |
CN110548004A (zh) * | 2018-05-30 | 2019-12-10 | 成都施贝康生物医药科技有限公司 | 一种稳定的丁苯酞大容量注射液及其制备方法 |
CN112386571A (zh) * | 2020-12-04 | 2021-02-23 | 成都施贝康生物医药科技有限公司 | 一种稳定的丁苯酞氯化钠注射液、其制备方法及用途 |
CN114685410A (zh) * | 2020-12-26 | 2022-07-01 | 四川汇宇制药股份有限公司 | 一种丁苯酞的制备方法 |
WO2023165094A1 (zh) * | 2022-03-04 | 2023-09-07 | 中国医学科学院药用植物研究所 | 一种羟戊苯甲酸双酯化合物及其制备方法和应用 |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8552058B2 (en) | 2004-06-18 | 2013-10-08 | CSPC Zhongqi Pharmaceutical Technology (Shijazhuang) Co., Ltd. | Application of L-n-butylphthalide in preventing and treating dementia |
CN100361656C (zh) * | 2004-08-27 | 2008-01-16 | 石药集团中奇制药技术(石家庄)有限公司 | 丁苯酞自乳化释药体系及其制备方法和应用 |
CN101342152B (zh) * | 2007-07-10 | 2010-10-13 | 石药集团中奇制药技术(石家庄)有限公司 | 丁苯酞片及其制备方法 |
CN103505409B (zh) * | 2012-06-27 | 2017-12-26 | 石药集团中奇制药技术(石家庄)有限公司 | 一种丁苯酞注射液及其制备方法 |
CN103784424B (zh) * | 2012-10-30 | 2018-04-27 | 石药集团中奇制药技术(石家庄)有限公司 | 一种丁苯酞经皮贴剂及其制备方法 |
CN103127025B (zh) * | 2013-03-06 | 2016-03-09 | 石家庄鸯星科技有限公司 | 消旋2-(α-羟基戊基)苯甲酸盐片的制备方法 |
CN105380908B (zh) * | 2015-12-09 | 2018-08-10 | 河北大学 | 一种丁苯酞药物复合物及其制备方法和缓释制剂 |
CN108553412B (zh) * | 2018-05-14 | 2019-10-29 | 田普森 | 一种含丁苯酞与增溶剂药物组合物 |
CN111743892A (zh) * | 2019-03-26 | 2020-10-09 | 石家庄以岭药业股份有限公司 | 丁苯酞衍生物在制备治疗心梗或其相关疾病药物中的应用 |
CN112999175B (zh) * | 2021-04-26 | 2021-08-03 | 奥信阳光(北京)药业科技有限公司 | 一种丁苯酞口服冻干粉及其制备方法和用途 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4727064A (en) * | 1984-04-25 | 1988-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Pharmaceutical preparations containing cyclodextrin derivatives |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1048158C (zh) | 1993-09-09 | 2000-01-12 | 中国医学科学院药物研究所 | 芹菜甲素在制备预防和治疗哺乳动物或人类脑缺血引起的疾病的药中的应用 |
CN1086942C (zh) * | 1998-12-18 | 2002-07-03 | 中国医学科学院药物研究所 | 丁基苯酞在制备抗血栓形成及抗血小板聚集药物中的应用 |
CN1136209C (zh) * | 1999-07-05 | 2004-01-28 | 中国医学科学院药物研究所 | 制备光学活性3-正丁苯酞的方法 |
-
2002
- 2002-08-21 CA CA2494157A patent/CA2494157C/en not_active Expired - Lifetime
- 2002-08-21 BR BR0215848-5A patent/BR0215848A/pt not_active Application Discontinuation
- 2002-08-21 DE DE60238510T patent/DE60238510D1/de not_active Expired - Lifetime
- 2002-08-21 US US10/524,653 patent/US20060166931A1/en not_active Abandoned
- 2002-08-21 JP JP2004529646A patent/JP4378755B2/ja not_active Expired - Lifetime
- 2002-08-21 AU AU2002327307A patent/AU2002327307B8/en not_active Expired
- 2002-08-21 DK DK02760059.2T patent/DK1535916T3/da active
- 2002-08-21 EP EP02760059A patent/EP1535916B1/en not_active Expired - Lifetime
- 2002-08-21 AT AT02760059T patent/ATE489972T1/de active
- 2002-08-21 WO PCT/CN2002/000579 patent/WO2004018444A1/zh active Application Filing
- 2002-08-21 ES ES02760059T patent/ES2355133T3/es not_active Expired - Lifetime
-
2005
- 2005-02-04 NO NO20050629A patent/NO20050629L/no not_active Application Discontinuation
- 2005-08-03 HK HK05106659.4A patent/HK1074200A1/xx not_active IP Right Cessation
-
2008
- 2008-08-28 US US12/200,130 patent/US7678776B2/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4727064A (en) * | 1984-04-25 | 1988-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Pharmaceutical preparations containing cyclodextrin derivatives |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070112065A1 (en) * | 2003-10-10 | 2007-05-17 | Shijiazhuang Pharma. Group Zhongqi Pharmaceutical | Use of l-butylphthalide in the manufacture of medicaments for prevention and treatment of cerebral infarct |
US8598225B2 (en) | 2003-10-10 | 2013-12-03 | Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. | Use of L-butylphthalide in the manufacture of medicaments for treatment of cerebral infarct |
US20070134316A1 (en) * | 2003-12-05 | 2007-06-14 | Shijiazhuang Pharma. Group Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. | Soft capsule of butylphthalide and a process for preparing the same |
US10463614B2 (en) | 2005-12-16 | 2019-11-05 | Shijiazhuang Pharma Group Nbp Pharmaceutical Co. | Butylphthalide intravenous emulsion and application thereof |
CN110548004A (zh) * | 2018-05-30 | 2019-12-10 | 成都施贝康生物医药科技有限公司 | 一种稳定的丁苯酞大容量注射液及其制备方法 |
CN112386571A (zh) * | 2020-12-04 | 2021-02-23 | 成都施贝康生物医药科技有限公司 | 一种稳定的丁苯酞氯化钠注射液、其制备方法及用途 |
CN114685410A (zh) * | 2020-12-26 | 2022-07-01 | 四川汇宇制药股份有限公司 | 一种丁苯酞的制备方法 |
WO2023165094A1 (zh) * | 2022-03-04 | 2023-09-07 | 中国医学科学院药用植物研究所 | 一种羟戊苯甲酸双酯化合物及其制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
DE60238510D1 (de) | 2011-01-13 |
NO20050629L (no) | 2005-03-17 |
HK1074200A1 (en) | 2005-11-04 |
US20080318898A1 (en) | 2008-12-25 |
EP1535916A4 (en) | 2006-09-20 |
ES2355133T3 (es) | 2011-03-23 |
EP1535916A1 (en) | 2005-06-01 |
JP2006500367A (ja) | 2006-01-05 |
AU2002327307B8 (en) | 2009-02-26 |
BR0215848A (pt) | 2005-06-21 |
EP1535916B1 (en) | 2010-12-01 |
JP4378755B2 (ja) | 2009-12-09 |
DK1535916T3 (da) | 2011-03-14 |
US7678776B2 (en) | 2010-03-16 |
CA2494157A1 (en) | 2004-03-04 |
AU2002327307B2 (en) | 2009-02-12 |
ATE489972T1 (de) | 2010-12-15 |
WO2004018444A1 (fr) | 2004-03-04 |
AU2002327307A1 (en) | 2004-03-11 |
CA2494157C (en) | 2010-10-12 |
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