CN100415241C - Medicinal composition for treating cardio-cerebrovascular diseases - Google Patents
Medicinal composition for treating cardio-cerebrovascular diseases Download PDFInfo
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- CN100415241C CN100415241C CNB200310100813XA CN200310100813A CN100415241C CN 100415241 C CN100415241 C CN 100415241C CN B200310100813X A CNB200310100813X A CN B200310100813XA CN 200310100813 A CN200310100813 A CN 200310100813A CN 100415241 C CN100415241 C CN 100415241C
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Abstract
The present invention discloses medicine for treating cardiovascular and cerebrovascular diseases. The medicine is prepared from the following two kinds of raw material: ginseng stem and leaf saponin extracted from stems and leaves of ginseng, and red sage root phenolic acid extracted from red sage root. The medical composition of the present invention can activate blood circulation, remove blood stasis, benefit qi, promote the production of the body fluid, and enhance the immunizing power of a human body. Qi and blood are simultaneously treated. The synergistic action is generated. The therapeutic effect is obviously enhanced. Compared with the effect of the same dose of ginseng stem and leaf saponin singly used or the effect of the same dose of red sage root phenolic acid singly used, the effect of the present invention is greatly improved.
Description
Affiliated technical field
The present invention relates to a kind of medicine for the treatment of cardiovascular and cerebrovascular disease, specifically the pharmaceutical composition of the effective site of the effective site of Stem and leaf of Radix Ginseng and Radix Salviae Miltiorrhizae composition.
Background technology
Motherland's medical science thinks that " the capable then blood of gas is capable, and the stagnation of QI is blood stasis then " influences each other between gas, the blood, again mutual dependence for existence.Motherland's traditional medicine thinks that the main pathogenesis of cardiovascular and cerebrovascular disease such as coronary heart disease is a blood stasis due to qi deficiency, so its main rule of treatment is a benefiting QI for activating blood circulation, the operation of blood simultaneously produces obstacle, make the nutritional labeling of absorption of human body be difficult to effectively be transported to corresponding organ, thereby the immunity degradation that causes human body, the state of an illness is further increased the weight of, can produce other complication.The conventional medicament of existing treatment cardiovascular and cerebrovascular disease is Chinese crude drug and their prescription mostly, through simple water or alcoholic acid extraction and make, composition is unclear, be difficult to after the extraction guarantee that effective ingredient has obtained preservation, as Radix Salviae Miltiorrhizae Tabellae, through after the water boiling and extraction, its aqueous soluble active constituent is destroyed, makes drug effect reduce greatly.Existing simultaneously medicine seldom can benefiting QI for activating blood circulation, can improve the immunity of human body again.
Stem and leaf of Radix Ginseng is a QI invigorating simply, the Chinese medicine that promotes the production of body fluid, the stem and leaf of Radix Ginseng saponin is an effective ingredient wherein, have and the proximate effect of Radix Ginseng, but effect is gentle, there is not the ginseng qi-tonifying effect strong, but the dry property when also not having ginseng qi-tonifying, the effect that have the yin nourishing of promoting the production of body fluid simultaneously, improves body immunity replaces Radix Ginseng with Stem and leaf of Radix Ginseng, draw the tonification function of Radix Ginseng, dispeled the dry property of Radix Ginseng again.But Stem and leaf of Radix Ginseng does not have function of promoting blood circulation to disperse blood clots.
Radix Salviae Miltiorrhizae is a Chinese medicine simply, effect with blood circulation promoting and blood stasis dispelling, modern pharmacological research shows, the main effective site of Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling is salvianolic acid wherein, it has the effect of microcirculation improvement preferably, simultaneously salvianolic acid has very strong antioxidation, thereby has good effect for the ischemical reperfusion injury that alleviates after cerebral infarction, the myocardial infarction, and salvianolic acid B wherein is the most effective composition; But salvianolic acid is thermo-labile, acid and alkali-resistance not.The existing commercially available injection that contains salvia miltiorrhiza raw material, as Radix Salviae Miltiorrhizae Injection, FUFANG DANSHEN ZHUSHEYE, owing to adopt water boiling and extraction, the salvianolic acid decomposes becomes danshensu and certain toxic protocatechualdehyde is arranged, thereby the content of salvianolic acid is very low, and the effect of the blood circulation promoting and blood stasis dispelling of its preparation also decreases.Radix Salviae Miltiorrhizae has function of promoting blood circulation to disperse blood clots preferably, but its no QI invigorating effect.
Summary of the invention
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 tonifying QI to produce body fluid, again can activating blood circulation to dissipate blood stasis, can improve body immunity simultaneously, and QI and blood is ruled together, and produces synergism, raising evident in efficacy.
The technical solution adopted for the present invention to solve the technical problems is: a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, it is made up of the stem and leaf of Radix Ginseng saponin who extracts from Stem and leaf of Radix Ginseng and two kinds of raw materials of salvianolic acid of extracting from Radix Salviae Miltiorrhizae.
The raw materials used weight proportion of medicine of the present invention can for: from 1 part of stem and leaf of Radix Ginseng saponin, salvianolic acid 0.1-20 part.
The raw materials used preferred weight proportioning of medicine of the present invention is: from 1 part of stem and leaf of Radix Ginseng saponin, and salvianolic acid 0.3-15 part.
The raw materials used more preferably weight proportion of medicine of the present invention is: from 1 part of stem and leaf of Radix Ginseng saponin, salvianolic acid 0.5-10 part.
The raw materials used optimum weight proportioning of medicine of the present invention is: from 1 part of stem and leaf of Radix Ginseng saponin, and 3 parts of salvianolic acid.
The dosage form of medicine of the present invention can be any existing pharmaceutical dosage form in injection, transfusion, powder pin, drop pill, tablet, slow releasing tablet, capsule, soft capsule, the granule.
The cardiovascular and cerebrovascular disease that medicine of the present invention is controlled mainly comprises cerebral thrombosis, cerebral ischemia, coronary heart disease, angina pectoris, myocardial ischemia, heart failure, arrhythmia etc.
Pharmaceutical composition of the present invention is made various dosage forms by existing preparation process after can adopting conventional method with stem and leaf of Radix Ginseng saponin and salvianolic acid uniform mixing.The stem and leaf of Radix Ginseng saponin can adopt following method to extract from Stem and leaf of Radix Ginseng in the raw material: get the Stem and leaf of Radix Ginseng medical material, with ethanol or water extraction, collect extracting solution, concentrate, in concentrated solution, thin up staticly settles, and filters, and gets supernatant concentration and becomes rare extractum; Described rare extractum is crossed macroporous adsorbent resin, the low-concentration ethanol eluting of elder generation's water or 5-20%, remove the impurity that is dissolved in polar solvent, discarding need not, the high concentration ethanol eluting of reuse 40-95%, collect this high concentration ethanol eluent, the eluent drying with behind the recovery ethanol promptly gets the stem and leaf of Radix Ginseng saponin.Salvianolic acid can adopt following method to extract from Radix Salviae Miltiorrhizae: get red rooted salvia, use ethanol extraction, collect extracting solution, in the extracting solution after low-temperature reduced-pressure reclaims ethanol, thin up staticly settles, and filters, and gets supernatant concentration and becomes extractum; Described extractum is crossed macroporous adsorbent resin, and the low-concentration ethanol eluting of first water or 5-20% is removed the impurity that is dissolved in polar solvent, discard need not, the high concentration ethanol eluting of reuse 40-95% is collected this high concentration ethanol eluent, eluent drying with behind the recovery ethanol promptly gets salvianolic acid.
Compared with prior art, the invention has the beneficial effects as follows: this pharmaceutical composition becomes to distinguish one from the other, contain stem and leaf of Radix Ginseng saponin and salvianolic acid, it can activating blood circulation to dissipate blood stasis, again can tonifying QI to produce body fluid, simultaneously can improve body immunity, QI and blood is ruled together, and produces synergism, than singly using with the dosage stem and leaf of Radix Ginseng saponin or singly using effect all to improve greatly, prove that through pharmacodynamics test it is evident in efficacy with the dosage salvianolic acid; Simultaneously, the inventor has adopted new extracting method to salvia miltiorrhiza raw material, thereby has kept salvianolic acid preferably, has also reduced the content of protocatechualdehyde, when heightening the effect of a treatment, has reduced toxicity, has increased the safety of medication.
The curative effect of medicine of the present invention is proved by following pharmacodynamics test:
Because cardiovascular and cerebrovascular disease all can cause hemorheological change, so but designer's ginseng stem leaf saponin and salvianolic acid cause the pharmacodynamics test of the therapeutical effect of cerebral infarction to rat " rabbit brain powder-macromolecule glucosan ", investigate the change of hemorheological property behind the cerebral infarction to measure whole blood viscosity under the different shear rates, investigate erythrocyte deformability with erythrocyte albumen ringer solution viscosity, thereby investigation stem and leaf of Radix Ginseng saponin and salvianolic acid are to the therapeutical effect of cardiovascular and cerebrovascular disease.
Material: animal: rat, body weight 250-350g, male and female are regardless of.Equipment: cone and plate viscometer (homemade NZ-6 type), centrifuge, scale centrifuge tube, eye scissors, ophthalmology tweezer and operating theater instruments commonly used, 0 trumpeter's art silk thread, vascular clamp etc.Medicine and reagent: (salvianolic acid/stem and leaf of Radix Ginseng saponin is respectively the different proportionings of salvianolic acid and stem and leaf of Radix Ginseng saponin: medicine 10/0,15/1,10/1,7/1,5/1,3/1,1/1,0/10); With commercially available RENSHEN JINGYEZAOGAN ZHUSHEYE, the positive medicine contrast of Radix Salviae Miltiorrhizae Injection; Rabbit brain powder (rabbit brain powder thromboplastin powder), the biochemical reagents experiment of Shanghai section is produced.Get the rabbit brain powder between the sub-sieve 120-150 order, granule is 100-120 m.Macromolecule glucosan: molecular weight 5,000,000.The preparation of suppository: the 25mg rabbit brain powder is mixed in 10% macromolecule dextran solution 100ml, place 37 ℃ of water-baths 40 minutes.Then, it is standby to be put in-18 ℃ of refrigerators.Quick medical ZT glue (Xi'an Research Inst. of Chemical Industry's production).BSA, ringer solution.Heparin sodium: press 20u/ml blood dosage and add test tube, 40 ℃ of following dry for standby.
Test method: 1, the rat cerebral infarction model prepares: the rat etherization, and it is fixing to lie on the back, skin cropping sterilization, cervical region cuts, and neck always beats one's brains on the left of separating, neck is interior, external carotid artery.Folder closes external carotid artery, common carotid artery proximal part respectively.Press from both sides a vascular clamp again at the distal end place.After suppository shaken up, lunge common carotid artery by 0.03ml/100g rat dosage, open the distal end vascular clamp, suppository is injected with the 0.25ml syringe.Then, folder closes the common carotid artery distal end, extracts syringe needle, closes pin hole with medical adhesive dressing.Decontrol the vascular clamp of common carotid artery distal end, proximal part, external carotid artery after 1 minute successively, recover blood flow, cleaning wound, skin suture.
The different proportioning medicines of salvianolic acid/stem and leaf of Radix Ginseng saponin to cerebral infarction after the hemorheology influence of different time: rat is divided into 2 hours groups, 3 days groups, organized in 9 days, every group is further divided into administration group (the different proportioning medicines of salvianolic acid/stem and leaf of Radix Ginseng saponin+animal model group), normal saline group (normal saline+animal model group), sham operated rats (matched group), every group of 12 rats.Administration group, normal saline group all impose operation technique as stated above, and the sham operated rats operation technique is identical, but not injected plug agent with the physiologic saline for substitute suppository, is injected in internal carotid artery.
The administration group is in preceding 1 hour intraperitoneal injection of drugs (salvianolic acid/stem and leaf of Radix Ginseng saponin, positive drug) 1.0mg/Kg of operation.The normal saline group is injected commensurability normal saline.Sham operated rats is not injected any medicine.Every morning administration 1 time after 3 days groups and the 9 days groups, for three days on end or 9 days.
2 hours after surgery, the 3rd day, the 9th day respectively, with rat anesthesia (25% urethane 0.3ml/100g body weight, lumbar injection), the right common carotid artery blood-letting was measured whole blood viscosity under the different shear rates with cone and plate viscometer in 2 hours in the heparin test tube.Again that whole blood is centrifugal with 1500rpm, inhale and remove upper plasma.Use 0.25% bovine serum albumin-ringer solution rinsing erythrocyte then three times, centrifugal 10 minutes of each 1500rpm.At last, in vitro be mixed with erythrocyte at scale: albumen was appointed the erythrocyte albumen ringer solution of liquid=6: 4, at 20 seconds
-1Shear rate is measured its viscosity down.With erythrocyte albumen ringer solution viscosity as erythrocyte deformability.All experiments are all carried out under 25 ℃ of constant temperature, and experimental result is carried out statistical test.Concrete numerical value and the results are shown in Table one, table two.
By table one result of the test as can be known, block back 2 hours after, whole blood viscosity is respectively organized equal no significant difference.When blocking 3 days, the normal saline group is compared with sham operated rats, whole blood viscosity rising (P＜0.05), animal model modeling success is described, each administration group all can reduce whole blood viscosity to some extent, wherein with salvianolic acid/stem and leaf of Radix Ginseng saponin's 5/1,3/1 effect best (P＜0.01), salvianolic acid/stem and leaf of Radix Ginseng saponin's 15/1,10/1,7/1,1/1 effect is taken second place, and the stem and leaf of Radix Ginseng saponin uses than single with stem and leaf of Radix Ginseng saponin or single effective with salvianolic acid with the salvianolic acid proportioning.When blocking after 9 days, the normal saline group is an abnormality still with sham operated rats ratio, hemorheology, and whole blood viscosity further increases the weight of.Each administration group and normal saline group ratio, whole blood viscosity descends, statistical procedures has the significance meaning, wherein with salvianolic acid/stem and leaf of Radix Ginseng saponin 10/1,7/1,5/1,3/1,1/1, effect best (P＜0.01), salvianolic acid/stem and leaf of Radix Ginseng saponin's 15/1 effect is taken second place, the stem and leaf of Radix Ginseng saponin uses than single with the salvianolic acid proportioning and uses salvianolic acid effective with stem and leaf of Radix Ginseng saponin or list, and effect all is better than RENSHEN JINGYEZAOGAN ZHUSHEYE and Radix Salviae Miltiorrhizae Injection.
By table two result of the test as can be known, block back 2 hours after, normal saline group and administration group erythrocyte deformability descend, each administration group is lower slightly than normal saline group numerical value, but effect is very unobvious.When blocking 3 days, the normal saline group is compared with sham operated rats, erythrocyte deformability further descends, in each administration group, salvianolic acid/stem and leaf of Radix Ginseng saponin 10/0 can stop erythrocyte deformability decline (P＜0.05) to a certain extent, salvianolic acid/stem and leaf of Radix Ginseng saponin 15/1,10/1,7/1,5/1,3/1,1/1 and sham operated rats are approaching, effect best (P＜0.01).The stem and leaf of Radix Ginseng saponin uses than single with stem and leaf of Radix Ginseng saponin or single effective with salvianolic acid with the salvianolic acid proportioning.When blocking after 9 days, normal saline group and sham operated rats ratio, erythrocyte deformability further descends.Each administration group and normal saline group ratio, all can improve and stop the decline of erythrocyte deformability, statistical procedures has significance meaning (P＜0.05), wherein can strengthen erythrocyte deformability (P＜0.01) with salvianolic acid/stem and leaf of Radix Ginseng saponin 15/1,10/1,7/1,5/1,3/1,1/1.The stem and leaf of Radix Ginseng saponin uses than single with the salvianolic acid proportioning and uses salvianolic acid effective with stem and leaf of Radix Ginseng saponin or list, and effect all is better than commercially available RENSHEN JINGYEZAOGAN ZHUSHEYE and Radix Salviae Miltiorrhizae Injection.
In sum, perform the operation after 2 hours, rat is existing hemorheological unusual.Blocked 3-9 days, hemorheology unusually further increases the weight of, and shows as whole blood viscosity and raises degradation under the erythrocyte deformability.Stem and leaf of Radix Ginseng saponin and salvianolic acid proportioning medicine can play and improve blood flow Denaturation behind the cerebral infarction, after the 3rd day, then can correct unusual hemorheology significantly and change.And effect with dosage Radix Salviae Miltiorrhizae Saponin or independent the use with the dosage stem and leaf of Radix Ginseng saponin, also is better than commercially available RENSHEN JINGYEZAOGAN ZHUSHEYE and Radix Salviae Miltiorrhizae Injection significantly better than independent use.Wherein, the best proportioning of effect is a salvianolic acid: stem and leaf of Radix Ginseng saponin=3: 1.
The specific embodiment
The present invention is described in further detail below in conjunction with the specific embodiment.
Embodiment one
Get stem and leaf of Radix Ginseng saponin 10g, salvianolic acid 1g, vegetable oil 25g, mixing is made capsule casing material with gelatin, is pressed into soft capsule, promptly makes the pharmaceutical composition of the soft capsule dosage form that contains 1 part of stem and leaf of Radix Ginseng saponin and 0.1 part of salvianolic acid.
Embodiment two
Get stem and leaf of Radix Ginseng saponin 1g, salvianolic acid 20g is dissolved in the 1000ml water for injection, adopts existing preparation of injection, promptly makes the pharmaceutical composition of the injectable powder type that contains 1 part of stem and leaf of Radix Ginseng saponin and 20 parts of salvianolic acid.
Embodiment three
Get stem and leaf of Radix Ginseng saponin 10g, salvianolic acid 3g, starch 100g, mix homogeneously adopts capsules preparation technique, promptly makes the pharmaceutical composition of the capsule formulation that contains 1 part of stem and leaf of Radix Ginseng saponin and 0.2 part of salvianolic acid.
Embodiment four
Get stem and leaf of Radix Ginseng saponin 1g, salvianolic acid 15g, mix homogeneously adopts drop pill preparation technology, promptly makes the pharmaceutical composition of the drops that contains 1 part of stem and leaf of Radix Ginseng saponin and 15 parts of salvianolic acid.
Embodiment five
Get stem and leaf of Radix Ginseng saponin 10g, salvianolic acid 5g, sucrose 80g, mix homogeneously is granulated, and sieves, and drying promptly makes the granule forms of pharmaceutical compositions that contains 1 part of stem and leaf of Radix Ginseng saponin and 1 part of salvianolic acid; Maybe with the further tabletting of granule warp that makes, drying promptly makes and contains 1 part of stem and leaf of Radix Ginseng saponin and 0.The pharmaceutical composition of the Tabules of 5 parts of salvianolic acid.
Embodiment six
Get stem and leaf of Radix Ginseng saponin 2g, salvianolic acid 20g, polyethylene 60g, mix homogeneously is granulated, tabletting, drying promptly makes the pharmaceutical composition of the slow releasing tablet dosage form that contains 1 part of stem and leaf of Radix Ginseng saponin and 10 parts of salvianolic acid.
Embodiment seven
Get stem and leaf of Radix Ginseng saponin 5g, salvianolic acid 15g is dissolved in the 1000ml water for injection, adopts process for preparation of injection, promptly makes injection (the containing transfusion) forms of pharmaceutical compositions that contains 1 part of stem and leaf of Radix Ginseng saponin and 3 parts of salvianolic acid.
More than the raw material that adopts among each embodiment, the stem and leaf of Radix Ginseng saponin can make by following method: get the Stem and leaf of Radix Ginseng medical material, with ethanol or water extraction, collect extracting solution, concentrate, in concentrated solution, thin up staticly settles, and filters, and gets supernatant concentration and becomes rare extractum; Described rare extractum is crossed macroporous adsorbent resin, the low-concentration ethanol eluting of elder generation's water or 5-20%, remove the impurity that is dissolved in polar solvent, discarding need not, the high concentration ethanol eluting of reuse 40-95%, collect this high concentration ethanol eluent, the eluent drying with behind the recovery ethanol promptly gets the stem and leaf of Radix Ginseng saponin.
Salvianolic acid can make by following method: get red rooted salvia, use ethanol extraction, collect extracting solution, in the extracting solution after reclaiming ethanol, thin up staticly settles, and filters, and gets supernatant concentration and becomes extractum; Described extractum is crossed macroporous adsorbent resin, and the low-concentration ethanol eluting of first water or 5-20% is removed the impurity that is dissolved in polar solvent, discard need not, the high concentration ethanol eluting of reuse 40-95% is collected this high concentration ethanol eluent, eluent drying with behind the recovery ethanol promptly gets salvianolic acid.
Claims (5)
1. pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, it is made up of the stem and leaf of Radix Ginseng saponin who extracts from Stem and leaf of Radix Ginseng and two kinds of raw materials of salvianolic acid of extracting from Radix Salviae Miltiorrhizae, it is characterized in that: the weight proportion of described two kinds of raw materials is: 1 part of stem and leaf of Radix Ginseng saponin, salvianolic acid 1-15 part;
Described stem and leaf of Radix Ginseng saponin's preparation method is: get the Stem and leaf of Radix Ginseng medical material, with ethanol or water extraction, collect extracting solution, concentrate, in concentrated solution, thin up staticly settles, and filters, and gets supernatant concentration and becomes rare extractum; Described rare extractum is crossed macroporous adsorbent resin, the low-concentration ethanol eluting of elder generation's water or 5-20%, remove the impurity that is dissolved in polar solvent, discarding need not, the high concentration ethanol eluting of reuse 40-95%, collect this high concentration ethanol eluent, the eluent drying with behind the recovery ethanol promptly gets the stem and leaf of Radix Ginseng saponin;
Described salvianolic acid preparation method is: get red rooted salvia, use ethanol extraction, collect extracting solution, in the extracting solution after low-temperature reduced-pressure reclaims ethanol, thin up staticly settles, and filters, and gets supernatant concentration and becomes extractum; Described extractum is crossed macroporous adsorbent resin, and the low-concentration ethanol eluting of first water or 5-20% is removed the impurity that is dissolved in polar solvent, discard need not, the high concentration ethanol eluting of reuse 40-95% is collected this high concentration ethanol eluent, eluent drying with behind the recovery ethanol promptly gets salvianolic acid.
2. the pharmaceutical composition of treatment cardiovascular and cerebrovascular disease according to claim 1 is characterized in that: the weight proportion of described two kinds of raw materials is: 1 part of the stem and leaf of Radix Ginseng saponin who extracts from Stem and leaf of Radix Ginseng, the salvianolic acid 1-10 part that extracts in the Radix Salviae Miltiorrhizae.
3. the pharmaceutical composition of treatment cardiovascular and cerebrovascular disease according to claim 2 is characterized in that: the weight proportion of described two kinds of raw materials is: 1 part of the stem and leaf of Radix Ginseng saponin who extracts from Stem and leaf of Radix Ginseng, the salvianolic acid 1-5 part that extracts in the Radix Salviae Miltiorrhizae.
4. the pharmaceutical composition of treatment cardiovascular and cerebrovascular disease according to claim 3 is characterized in that: the weight proportion of described two kinds of raw materials is: 1 part of the stem and leaf of Radix Ginseng saponin who extracts from Stem and leaf of Radix Ginseng, 3 parts of the salvianolic acid that extracts in the Radix Salviae Miltiorrhizae.
5. according to claim 1 or 2 or the pharmaceutical composition of 3 or 4 described treatment cardiovascular and cerebrovascular disease, it is characterized in that: its dosage form is any existing pharmaceutical dosage form in injection, powder pin, drop pill, tablet, capsule, the granule.
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| CN101292987B (en) * | 2007-04-29 | 2010-06-30 | 北京本草天源药物研究院 | Pharmaceutical combination |
| CN102058599B (en) * | 2009-11-17 | 2014-06-04 | 中国科学院上海药物研究所 | Salvianolate, and preparation method and application thereof |
| WO2016033727A1 (en) * | 2014-09-01 | 2016-03-10 | 广州市香雪制药股份有限公司 | Medicine for preventing and treating vascular diseases and preparation method thereof |
| CN105287670A (en) * | 2015-10-19 | 2016-02-03 | 遵义医学院 | Application of total saponins of Ginseng stems and leaves |
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Non-Patent Citations (2)
| Title |
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| 双参注射液急性毒性与安全性实验的研究. 白明学等.河南中医药学刊，第15卷第2期. 2000 |
| 双参注射液急性毒性与安全性实验的研究. 白明学等.河南中医药学刊，第15卷第2期. 2000 * |
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Effective date of registration: 20081205 Address after: Room 420, Goldman Sachs center, No. 2 Gaosheng East Road, Sichuan, Chengdu Patentee after: Chen Jin Address before: High tech Zone of Chengdu City, Sichuan Province, Gaopeng Road No. 2 Patentee before: Hekang Medicine Industry Co., Ltd., Chengdu |
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Owner name: CHEN JIN Free format text: FORMER OWNER: HEKANG PHARMACEUTICAL LLC, CHENGDU Effective date: 20081205 |
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Assignee: Chengdu Jinhua Pharmaceutical Co., Ltd. Assignor: Chen Jin Contract fulfillment period: 2009.3.18 to 2019.3.17 Contract record no.: 2009510000135 Denomination of invention: Cardiac and cerebral vascular disease treating medicinal composition Granted publication date: 20080903 License type: Exclusive license Record date: 20091029 |
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Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.3.18 TO 2019.3.17; CHANGE OF CONTRACT Name of requester: CHENGDU JINHUA PHARMACEUTICAL CO., LTD Effective date: 20091029 |
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Addressee: Chen Jin Document name: Notification of Termination of Patent Right |
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Granted publication date: 20080903 Termination date: 20121003 |