CN1843350A - Pharmaceutical composition for treating cardiovascular and cerebrovascular disease - Google Patents

Pharmaceutical composition for treating cardiovascular and cerebrovascular disease Download PDF

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Publication number
CN1843350A
CN1843350A CN 200510129391 CN200510129391A CN1843350A CN 1843350 A CN1843350 A CN 1843350A CN 200510129391 CN200510129391 CN 200510129391 CN 200510129391 A CN200510129391 A CN 200510129391A CN 1843350 A CN1843350 A CN 1843350A
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China
Prior art keywords
pharmaceutical composition
bilobalide
salt
pharmaceutically acceptable
acid
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CN 200510129391
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Chinese (zh)
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CN100488503C (en
Inventor
郑伟
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Haisike Pharmaceutical Group Limited by Share Ltd
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CHENGDU BOLING PHARMACEUTICAL Co Ltd
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Priority claimed from CNA2005100206683A external-priority patent/CN1726923A/en
Application filed by CHENGDU BOLING PHARMACEUTICAL Co Ltd filed Critical CHENGDU BOLING PHARMACEUTICAL Co Ltd
Priority to CNB2005101293918A priority Critical patent/CN100488503C/en
Publication of CN1843350A publication Critical patent/CN1843350A/en
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Publication of CN100488503C publication Critical patent/CN100488503C/en
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  • Medicines Containing Plant Substances (AREA)
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Abstract

The invention discloses a medicament for treating cardiovascular and cerebrovascular diseases, which mainly comprises bilobalide and polyene phosphatidyl choline. The effects of the composition include improving blood flow volume for the patients of cerebrovascular disease, and increasing the phosphorus content in phosphatide tissue.

Description

A kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease
What the present invention relates to is a kind of medicine with the effect of treatment cardiovascular and cerebrovascular disease.
Bilobalide is by the important effective ingredient of a class that extracts in the Folium Ginkgo, mainly contains ginkalide A, B and a spot of ginkalide C, and other also contain bilobalide J, M and the bilobalide etc. of trace.Pharmacological research shows that bilobalide is natural efficiently antiplatelet activity factor (PAF) receptor antagonist, but anticoagulant reduces blood viscosity, improves ischemia patient's microcirculation, reduce thrombosis, the very potential medicine for the treatment of cardiovascular and cerebrovascular disease clinically that becomes.At present domestic existing numerous producers are being developed as bilobalide the medicine of injection type.
Soybean phospholipid (English name Soya Lecithin) is a kind of medical substance that extracts from Semen sojae atricolor, has another name called soybean lecithin, is pharmaceuticals industry medicinal raw material commonly used.Soybean phospholipid includes abundant phosphatidylcholine (English name Phosphatidyl choline), and contains abundant conjunction type unsaturated fatty acid, is mainly linoleic acid, linolenic acid and oleic acid etc.China has the soybean phospholipid raw material and the related preparations production and selling thereof of national standard at present.
Polyene phosphatidylcholine is that soybean phospholipid is further purified the high-purity soybean phospholipid that processing makes, include abundant conjunction type unsaturated fatty acid, be mainly linoleic acid, linolenic acid and oleic acid etc., the present approved of China production and sale that should the product raw material.Polyene phosphatidylcholine is consistent with important endogenous phospholipid on chemical constitution, and is better than the latter on function, and its preparation is mainly used in the various types of hepatopathys of treatment clinically.As: hepatitis, liver cirrhosis, hepatic necrosis, hepatic coma, fatty liver and cholestasis etc., existing polyene phosphatidylcholine capsule of China and injection import thereof at present.
Comprehensive, though it is numerous to treat the medicine of cardiovascular and cerebrovascular diseases such as apoplexy, myocardial infarction at present clinically, the Western medicine or the single chemical drugs mechanism of action are single, and combined therapy effect is unsatisfactory basically clinically; Chinese medicine has the effect of multimachine reason Synergistic treatment, clinical in recent years consumption increases rapidly, because at present common Chinese medicine complicated component is unclear, adverse reaction rate is higher, the onset of oral Chinese medicine preparation is slow, and such medicine does not satisfy the requirement of clinical patients yet.Be badly in need of definite ingredients, cardiovascular and cerebrovascular diseases medicine safely and effectively at present clinically.
Purpose of the present invention just provides a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, and this pharmaceutical composition can produce comprehensive synergism, significantly is better than singly using the effect with the dosage bilobalide.
Technical problem to be solved by this invention is to realize by following technical scheme, it is made up of bilobalide and two kinds of raw materials of polyene phosphatidylcholine, wherein bilobalide can be replaced (with the bilobalide total amount conversion that includes) with Folium Ginkgo extract or its pharmaceutically acceptable property salt of significant proportion amount, and polyene phosphatidylcholine can be replaced (calculating with the pure product of phosphatidylcholine that indicate) with the soybean phospholipid of significant proportion amount.The weight ratio of bilobalide and polyene phosphatidylcholine is generally 1: 1-30 is preferably 1: 10.Add a certain amount of cholic acid or its pharmaceutically acceptable property salt, dehydrocholic acid or its pharmaceutically acceptable property salt, deoxycholic acid or its pharmaceutically acceptable property salt, glycocholic acid or its pharmaceutically acceptable property salt in the drug prescription as adjuvant, to improve the solubility property of principal agent bilobalide and polyene phosphatidylcholine.
The curative effect of pharmaceutical composition of the present invention is proved by following pharmacodynamics test:
1, dog middle cerebral artery ligation cerebral ischemic model test
Material: animal: Chinese grass seeds dog, body weight 8-12kg; Medicine: bilobalide injection (20mg/ props up) and compound gingkgo lactone Polyene Phosphatidylcholine injection liquid (20+200mg/ props up), self-control.
Table one is subjected to the influence of reagent product to experimental dog cerebral ischemia
Group Matched group Test group
Be subjected to the reagent product Bilobalide injection Compound gingkgo lactone Polyene Phosphatidylcholine injection liquid
Brain weight 65.58±2.4 62.36±5.7
Cerebral tissue ischemic region weight 13.98±2.8 10.58±3.6
Ischemic region brain anharmonic ratio (%) 21.31 16.96
Cephalin rate of descent (%) 34% 10%
Table one result shows and the matched group medicine compares, and the test group medicine can significantly reduce ischemic region brain anharmonic ratio, significantly reduces the decline of cephalin, and brain function is had better protective effect.
2, dog anterior descending coronary caused by ligature myocardial infarction model test
Table two is subjected to the influence of reagent product to the test of myocardial infarction canine model
Group Matched group Test group
Bilobalide injection Compound gingkgo lactone Polyene Phosphatidylcholine injection liquid
LDH(U/L) Before the ligation 68.90±10.68 71.32±8.46
After the ligation 122.67±20.82 98.43±10.31
CPK(U/L) Before the ligation 67.19±15.39 66.48±8.72
After the ligation 146.43±93.79 123.12±41.56
Left side chamber infarction size (%) 13.23±1.56 9.32±1.78
By table two as seen and matched group relatively, the test group medicine can significantly reduce LDH and the CPK of animal pattern, obviously dwindles the left ventricle infarction size, and heart is had the better protection effect.
The present invention will be described with embodiment below, but the present invention is not limited to these embodiment.
Embodiment 1: soft capsule
Prescription 1 Prescription 2
Bilobalide polyene phosphatidylcholine vegetable oil deoxycholic acid 20mg 200mg 200mg 30mg Bilobalide soybean phospholipid (calculating) vegetable oil dehydrocholic acid with the pure product of phosphatidylcholine that include 20mg 200mg 180mg 30mg
Prescription 4 Prescription 3
Folium Ginkgo extract (calculating) soybean phospholipid (calculating) vegetable oil dehydrocholic acid with the pure product of phosphatidylcholine that include with the bilobalide that includes 20mg 200mg 180mg 30mg Folium Ginkgo extract (calculating) polyene phosphatidylcholine vegetable oil deoxycholic acid with the bilobalide that includes 20mg 200mg 200mg 30mg
Process example: get active component, vegetable oil is an amount of, the adding adjuvant, and mixing is pressed into soft capsule, promptly makes the pharmaceutical composition of the soft capsule dosage form that contains 1 part of bilobalide and 10 parts of polyene phosphatidylcholine.
Embodiment 2: capsule
Prescription 1 Prescription 2
Bilobalide polyene phosphatidylcholine cholic acid micropowder silica gel carboxymethyl starch sodium 20mg 200mg 30mg 30mg 100mg Bilobalide soybean phospholipid (calculating) dehydrocholic acid micropowder silica gel carboxymethyl starch sodium with the pure product of phosphatidylcholine that include 20mg 20mg 30mg 30mg 100mg
Process example: get active component, cholic acid, micropowder silica gel, carboxymethyl starch sodium mixing, last capsule filling machine, compacting obtains capsule.
Embodiment 3: injection with small volume
Prescription 1 Prescription 2
Bilobalide polyene phosphatidylcholine sodium cholate ethanol injection water 10mg 100mg 50mg is an amount of Bilobalide sodium salt (in bilobalide) polyene phosphatidylcholine sodium cholate ethanol injection water 1mg 30mg 15mg is an amount of
Prescription 3 Prescription 4
Bilobalide potassium salt (in bilobalide) soybean phospholipid sodium cholate ethanol injection water 10mg 100mg 50mg is an amount of Bilobalide Portugal ammonium carbamate (in bilobalide) polyene phosphatidylcholine sodium cholate ethanol injection water 10mg 100mg 50mg is an amount of
Prescription 5 Prescription 6
Folium Ginkgo extract (in bilobalide) polyene phosphatidylcholine sodium cholate ethanol injection water 10mg 100mg 50mg is an amount of Folium Ginkgo extract (in bilobalide) polyene phosphatidylcholine sodium cholate ethanol injection water 10mg 10mg 10mg is an amount of
Process example: get sodium cholate, add the suitable quantity of water dissolving and make sodium cholate solution; Get the principal agent of recipe quantity,, stir in the above-mentioned sodium cholate solution of adding to clarification with an amount of dissolve with ethanol, agitating solution is to clarification, add water for injection, regulator solution pH to 8 adds 0.3% active carbon, stirring at normal temperature 15 minutes, filter, fill the nitrogen packing, envelope bottle, sterilization, promptly.
Embodiment 4: freeze-dried powder
Prescription 1 Prescription 2
Ginkgolides Polyene Phosphatidylcholine natrium dehydrocholicum NaOH ethanol sweet mellow wine water for injection An amount of 15mg of 2mg 20mg 10mg is an amount of Ginkgolides soybean lecithin natrium dehydrocholicum NaOH ethanol sweet mellow wine water for injection An amount of 15mg of 2mg 20mg 10mg is an amount of
Process example: remove the hydrogen sodium cholate, add the suitable quantity of water dissolving and make the dehydrocholic acid sodium solution; Get the recipe quantity principal agent,, stir in the above-mentioned dehydrocholic acid sodium solution of adding to clarification with the amount of making dissolve with ethanol, agitating solution is to clarification, add mannitol, add water for injection, regulator solution pH to 8 adds 0.3% active carbon, stirring at normal temperature 15 minutes, filtration, lyophilization, promptly.
Bilobalide can directly be bought the commercially available prod, also can buy the commercially available Folium Ginkgo extract that contains bilobalide, and product quality should meet the requirement of Chinese Pharmacopoeia Folium Ginkgo extract quality standard, replaces with the total bilobalide conversion that includes when feeding intake.Polyene phosphatidylcholine can directly be bought the commercially available prod, and product quality should meet the national drug standards.Soybean phospholipid can be bought the commercially available prod of Shanghai Taiwei Pharmaceutical Co., Ltd., German Degussa company or German Lipoid company or other companies, and product quality should meet the national drug standards, replaces with the phosphatidylcholine conversion that includes when feeding intake.

Claims (8)

1. a pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease is characterized in that being made up of bilobalide and two kinds of raw materials of polyene phosphatidylcholine basically.
2. pharmaceutical composition according to claim 1 is characterized in that the weight proportion of described two kinds of raw materials is: 1 part of bilobalide, polyene phosphatidylcholine 1-30 part.
3. pharmaceutical composition according to claim 1 is characterized in that the bilobalide in the said composition can be replaced with the Folium Ginkgo extract that contains the significant proportion amount.
4. pharmaceutical composition according to claim 1 is characterized in that the bilobalide in the said composition can be replaced with its pharmaceutically acceptable property salt, as sodium salt, potassium salt, ammonium salt and meglumine salt etc.
5. as the described pharmaceutical composition of claim 1-4, wherein polyene phosphatidylcholine can be replaced (with the phosphatidylcholine conversion that includes) with the soybean phospholipid of significant proportion amount.
6. according to the described pharmaceutical composition of claim 1-5, its pharmaceutical dosage form is injection types such as injection, infusion solutions or lyophilized injectable powder.
7. according to the described pharmaceutical composition of claim 1-5, its pharmaceutical dosage form is peroral dosage forms such as granule, conventional tablet, slow releasing tablet, dispersible tablet, capsule, soft capsule, micropill, oral dry gels or drop pill.
8. according to the described pharmaceutical composition of claim 1-7, contain at least a following pharmaceutic adjuvant in the used adjuvant: cholic acid or its pharmaceutically acceptable property salt, dehydrocholic acid or its pharmaceutically acceptable property salt, deoxycholic acid or its pharmaceutically acceptable property salt, glycocholic acid or its pharmaceutically acceptable property salt.
CNB2005101293918A 2005-04-06 2005-12-07 Pharmaceutical composition for treating cardiovascular and cerebrovascular disease Expired - Fee Related CN100488503C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNB2005101293918A CN100488503C (en) 2005-04-06 2005-12-07 Pharmaceutical composition for treating cardiovascular and cerebrovascular disease

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN200510020668.3 2005-04-06
CNA2005100206683A CN1726923A (en) 2005-04-06 2005-04-06 Combination of medication for treating cardiovascular diseases and cerebrovascular disease
CNB2005101293918A CN100488503C (en) 2005-04-06 2005-12-07 Pharmaceutical composition for treating cardiovascular and cerebrovascular disease

Publications (2)

Publication Number Publication Date
CN1843350A true CN1843350A (en) 2006-10-11
CN100488503C CN100488503C (en) 2009-05-20

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Owner name: XIZHANG KANGXIN PHARMACEUTICAL CO., LTD.

Free format text: FORMER OWNER: CHENGDU BORUI PHARMACEUTICAL SCIENCE AND TECHNOLOGY DEVELOPMENT

Effective date: 20090515

C41 Transfer of patent application or patent right or utility model
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Effective date of registration: 20090515

Address after: Tibet Shannan Zedang town Xiang Qu Road No. 8

Patentee after: Tibet Kangxin Pharmaceutical Co., Ltd.

Address before: B-C-36, building, high tech incubator Park, South extension Road, Tianfu Road, Sichuan, China

Patentee before: Chengdu Boling Pharmaceutical Co., Ltd.

EE01 Entry into force of recordation of patent licensing contract

Assignee: Sichuan Haisco Pharmaceutical Co.,Ltd.

Assignor: Tibet Kangxin Pharmaceutical Co., Ltd.

Contract fulfillment period: 2009.6.18 to 2014.6.18

Contract record no.: 2009510000035

Denomination of invention: Composition of medication for treating cardiovascular diseases and cerebrovascular diseases

Granted publication date: 20090520

License type: Exclusive license

Record date: 2009.9.16

LIC Patent licence contract for exploitation submitted for record

Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.6.18 TO 2014.6.18; CHANGE OF CONTRACT

Name of requester: SICHUAN HAISIKE PHARMACEUTICAL CO., LTD.

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Address after: 856000 Tibet Shannan Zedang town Xiang Qu Road No. 8

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Patentee before: Tibet Kangxin Pharmaceutical Co., Ltd.

C56 Change in the name or address of the patentee
CP01 Change in the name or title of a patent holder

Address after: 856000 Tibet Shannan Zedang town Xiang Qu Road No. 8

Patentee after: Tibet Haisco Pharmaceutical Group Co., Ltd.

Address before: 856000 Tibet Shannan Zedang town Xiang Qu Road No. 8

Patentee before: Tibetan Haisike Pharmaceutical Group Co., Ltd.

CP01 Change in the name or title of a patent holder

Address after: 856000 Tibet Shannan Zedang town Xiang Qu Road No. 8

Patentee after: Haisike Pharmaceutical Group Limited by Share Ltd

Address before: 856000 Tibet Shannan Zedang town Xiang Qu Road No. 8

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