CN1385163A - Process for preparing novel medicine for breviscapine having function of promoting blood circulation and removing blood stasis - Google Patents
Process for preparing novel medicine for breviscapine having function of promoting blood circulation and removing blood stasis Download PDFInfo
- Publication number
- CN1385163A CN1385163A CN 02116795 CN02116795A CN1385163A CN 1385163 A CN1385163 A CN 1385163A CN 02116795 CN02116795 CN 02116795 CN 02116795 A CN02116795 A CN 02116795A CN 1385163 A CN1385163 A CN 1385163A
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- China
- Prior art keywords
- agent
- scutellarin
- breviscapine
- pharmaceutical preparation
- slow
- Prior art date
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- DJSISFGPUUYILV-ZFORQUDYSA-N scutellarin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC(O)=CC=1)O2 DJSISFGPUUYILV-ZFORQUDYSA-N 0.000 title claims abstract description 57
- 239000003814 drug Substances 0.000 title claims abstract description 27
- 230000017531 blood circulation Effects 0.000 title abstract description 5
- 230000001737 promoting effect Effects 0.000 title abstract description 4
- 239000008280 blood Substances 0.000 title description 5
- 210000004369 blood Anatomy 0.000 title description 5
- 238000004519 manufacturing process Methods 0.000 title description 3
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- 229930190376 scutellarin Natural products 0.000 claims abstract description 26
- 239000003795 chemical substances by application Substances 0.000 claims description 59
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a slow-released medicine preparation with the function of promoting blood circulation, removing staiss, removing obstruction in the channels to relieve pain. In particular it is a slow-released medicine preparation containing breviscapine. The described breviscapine is scutellarin or 4-hydroxy ba icalein-7-O-beta-D-pyrangluconate methyl ester.
Description
Invention field:
The present invention relates to a kind of Chinese medicine slow releasing preparation, particularly contain the slow releasing preparation of Chinese medicine Herba Erigerontis extract.
Background of invention:
Breviscapine is the flavone composition that is extracted by the medical herbs Herba Erigerontis, is divided into breviscapine and scutellarin.Its beginning is used for the seventies in 20th century, mainly is used for diseases such as clinical treatment apoplexy sequela, coronary heart disease, angina pectoris with electuary, tablet, capsule, injection.In these preparations, all exist many weak points, as common tablet, capsule, electuary, treatment at patient is long use, and the natural plants medicament extract all exists onset characteristics more slowly, thus to the hemiplegia home-bound patient or aged coronary heart disease patient every day too much number of times to take medicine be disadvantageous; The mode of taking medicine for three times every day makes blood drug level be the peak valley effect in addition, is unfavorable for treatment of diseases; By the viewpoint of pharmacoeconomics, medicining mode once how will cause the doctor, protect, patient produce great sunk cost, thereby cause the huge waste of resource.And injection is because various factors, the existence of the safety issue that causes, and now the shiver with cold of extensively having been reported, arrhythmia, dyspnea even shock etc. all are great potential danger factors.Therefore, the generation of above-mentioned unfavorable factor is avoided in the positive novel form research of carrying out this medicine simultaneously, will very important practical significance be arranged to the effect of curing, protecting, patient's generation is very favourable.
Summary of the invention
The present invention is according to the characteristics of breviscapine, and the characteristic of treatment relevant disease, by the viewpoint of pharmacoeconomics, develop the sustained-release oral preparation of this medicine, compare with existing oral formulations, possess following characteristics: the peak valley effect that (1) has avoided medicine to produce in blood; (2) by the viewpoint of pharmacoeconomics, reduce sunk cost, avoided the waste of efficient resource; (3) being more conducive to patient takes for a long time; (4) effectiveness and the safety of this medicine have been guaranteed.
The slow releasing preparation of breviscapine of the present invention, its active component comprises scutellarin or breviscapine, be Herba Erigerontis extract, has similar therapeutic effect, scutellarin preferably wherein, the active component of preparation of the present invention can be the breviscapine of 90% above content, also can be lower than this content.The active component of preparation of the present invention can extract by common extracting method, and these extracting method all have description in textbook or relevant document.
The invention provides the slow releasing preparation prescription of breviscapine, preparation method and application, pharmaceutical formulation of the present invention is made up of the breviscapine of 5%-95% and the slow-release material of 5%-95%, available slow-release material such as cellulose family, it can be methylcellulose, ethyl cellulose, propyl cellulose, hydroxypropyl cellulose, microcrystalline Cellulose, hydroxypropyl emthylcellulose etc., the acroleic acid resin class, the stearic acid esters, other slow-release material comprises: starch, dextrin, sodium alginate, carbomer, PVP, lactose etc., these slow-release materials and breviscapine carry out compatibility by different proportion, make aquogel type, erosion type or non-erosion type slow releasing preparation, these slow releasing preparation can be peroral dosage form such as tablet, capsule, suspensoid, granule, pill, powder etc., also can be external preparation, as: patch.
Breviscapine slow release preparation of the present invention, wherein the amount of active component scutellarin or breviscapine is effectively to measure on the physiology, can be the 1mg-200mg/ agent, preferably 10mg-100mg/ agent, most preferably 30mg-120mg/ agent.
Breviscapine slow release preparation of the present invention can be by oral, and be administered once every day, each preferably 10mg-120mg/ agent of consumption.Be used for the treatment of cardiovascular and cerebrovascular disease and pain relieving.
Oral Breviscapine slow release preparation of the present invention can be made up of scutellarin 1mg-200mg/ agent, hydroxypropyl emthylcellulose 1-200mg/ agent, lactose 1-100mg/ agent, sodium alginate 1-100mg/ agent, carbomer 0.1-10mg/ agent, PVP 0.1-10mg/ agent.Pharmaceutical preparation of the present invention preferably is grouped into by following one-tenth
Scutellarin 10-60mg/ agent
Hydroxypropyl emthylcellulose (HPMC K15M) 10-60mg/ agent
Lactose 5-30mg/ agent
Sodium alginate 5-40mg/ agent
Carbomer 0.5-2mg/ agent
PVP alcoholic solution 0.5-2mg/ agent or be grouped into by following one-tenth
Breviscapine 10-60mg/ agent
Hydroxypropyl emthylcellulose (HPMC K15M) 10-60mg/ agent
Lactose 5-30mg/ agent
Sodium alginate 5-40mg/ agent
Carbomer 0.5-2mg/ agent
PVP alcoholic solution 0.5-2mg/ agent pharmaceutical preparation of the present invention most preferredly is grouped into by following one-tenth
Scutellarin 30.0mg/ agent
Hydroxypropyl emthylcellulose (HPMC K15M) 35.5mg/ agent
Lactose 15.0mg/ agent
Sodium alginate 20.0mg/ agent
Carbomer 1.0mg/ agent
PVP alcoholic solution 1.0mg/ agent
Oral Breviscapine slow release preparation of the present invention can be by mixing with medicinal slow-release material as the scutellarin or the breviscapine of active component, by the preparation method manufacturing of common sustained release pharmaceutical formulation.
Oral Breviscapine slow release preparation of the present invention can be produced as follows:
Active component breviscapine and hydroxypropyl emthylcellulose, lactose, sodium alginate, carbomer, PVP are sieved respectively, mix homogeneously, with ethanol or water is wetting agent system soft material, granulate, dry back granulate, add tabletting behind the magnesium stearate mixing, or directly make granule, or the granule gelatine capsule of packing into is made granule.
Slow-release patch of the present invention comprises drug storehouse layer and adhesion layer, backing protective layer, controlled release rete, and its host material can be polyacrylic resin class, polyisobutylene class or silicone glue class glue; The release-controlled film material can be ethylene and vinyl acetate copolymer (EVA film), polyethylene (PE film) or polyacrylic microporous membrane.Can contain the transdermal penetrating agent in the drug storehouse layer, these transdermal penetrating agents can be that sulfoxide class, pyrrolones, ethyl acetate, azone, menthol, Camphora, carbon chain lengths are one or two or more kinds the compound penetrating agent in alcohol of ten to 18 etc., and consumption is 0.2---20%., in drug storehouse layer and adhesion layer, also can not add the transdermal penetrating agent.
Slow-release patch of the present invention can prepare by the following method:
1. with breviscapine, transdermal penetrating agent, polymer latex and organic solvent mixing, paint certain thickness, make solvent evaporates in the glue through 50-150 ℃ of scope inner drying or air blast or alternate manner, remove partial solvent, make the drug storehouse layer and the adhesion layer of suitable viscosity.Can in drug storehouse layer and adhesion layer, not add the transdermal penetrating agent yet.
2. make drug storehouse layer, backing protective layer, controlled release rete, adhesion layer and antiseized protective layer compound by compound mode, be die-cut into a certain size and specification patch again.
3. patch of the present invention also can be only by above-mentioned drug storehouse layer, backing protective layer with antiseized protective layer is compound makes.
Slow-release patch of the present invention is by being pasted on chest or painful area, and once a day, each one pastes, and every subsides contain breviscapine 30mg.
The present invention will be further described by the following examples.
Embodiment:
Embodiment one: the scutellarin slow releasing tablet: the 30mg/ sheet
Scutellarin 30.0g
Hydroxypropyl emthylcellulose (HPMC K15M) 35.5g
Lactose 15.0g
Sodium alginate 20.0g
Carbomer 1.0g
The PVP alcoholic solution make altogether in right amount 1000 above material mixing is even, wet granulation, through granulate, drying, tabletting is made 1000 scutellarin slow releasing tablet.
Embodiment two scutellarin slow releasing capsule: 60mg/ grain
Scutellarin 60.0g
Hydroxypropyl emthylcellulose (HPMC K15M) 50.0g
Lactose 30.0g
Sodium alginate 40.0g
Carbomer 2.0g
The PVP alcoholic solution is an amount of
Make 1000 grains altogether with above material mixing, wet granulation, the granulate drying hard gelatin capsule of packing into No. 1.
Embodiment three breviscapine slow releasing tablet: 30mg/ sheet
Breviscapine 30.0g
Hydroxypropyl emthylcellulose (HPMC K15M) 35.5g
Lactose 15.0g
Sodium alginate 20.0g
Carbomer 1.0g
The PVP alcoholic solution is an amount of
Make altogether 1000 above material mixing is even, wet granulation, through granulate, drying, tabletting is made 1000.
Embodiment four breviscapine slow releasing capsule: 30mg/ grain
Breviscapine 30.0g
Hydroxypropyl emthylcellulose (HPMC K15M) 35.5g
Lactose 15.0g
Sodium alginate 20.0g
Carbomer 1.0g
The PVP alcoholic solution is an amount of
Make 1000 altogether with above material mixing, wet granulation, the granulate drying hard gelatin capsule of packing into No. 1.
Embodiment five scutellarin slow-release patchs
A: drug storehouse layer
Scutellarin 10%
Polyacrylic resin 60%
Ethyl acetate 30%
Lauryl alcohol 5%B: adhesion layer
Scutellarin 3%
Polyacrylic resin 65%
Ethyl acetate 32%
Lauryl alcohol 5%
The practical application of product and experiment content:
Pharmaceutical preparation of the present invention has the effect of blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain.Its experiment situation is as follows:
1, acute toxicity test: 10 of healthy mices, body weight 17-24g uses the water-soluble back of product of embodiment one to irritate stomach 0.4ml/10g (being equivalent to crude drug 80g/kg), and none is only dead to observe for 1 week.
2, to the influence of platelet aggregation function: the heart blood sampling, with blood: the ratio of 3.8% sodium citrate=9: 1 fully shakes up, and with 100 centrifugal 10min of per minute, obtains PRP under the room temperature.0.2mlPRP is put in the mensuration pipe, and other gets 0.2mlPRP and is put in the control tube, adds 40 μ M ADP solution, 20 μ l, makes concentration become 4 μ M.The product of embodiment one is made into 5% concentration with 0.1M phosphate buffer (PH7.2), adding medicinal liquid 10 μ l in measuring pipe and control tube respectively, stablize 2min after, add 40 μ lMADP solution, 20 μ l again, the record aggregate curve calculates.The result: it is 67.8% that concentration suppresses to assemble percentage rate when 20mg/ml.
3, to the influence of the Cavia porcellus coronary flow that exsomatizes: the results are shown in Table:
Coronary flow difference increment rate P investigational agent 16.23 ± 3.09 6.87 ± 1.62 53.6%＜0.01 matched groups 10.49 ± 1.99
From result of the test as can be known, the product of embodiment one and matched group comparison are having significant difference aspect the increase coronary perfusion.
3, the Medulla Leporis seu Oryctolagi blood flow is tested: with 10 of healthy male rabbits, body weight 2.5kg is after the urethane intravenous anesthesia, the ligation external carotid artery, entad hold and centrifugal end difference intubate at common carotid artery, join with the constant speed infusion pump respectively, give the product of rabbit 1g/kg embodiment one, contrast with the normal saline group, record the test group cerebral vascular resistance 25.86 ± 16.21mmHg that on average descends, the 42.36 ± 21.11mmHg that all descends under the peripheral vascular resistance, with matched group relatively, there is significant difference its P＜0.05.
4, analgesic test: get 30 of mices, divide physiology saline, morphine hydrochloride, investigational agent to divide three groups, observe the mice number of elements of the writhing response that each group occurs in 10 minutes, calculate the analgesia percentage rate of respectively organizing medicine, the results are shown in Table.
Analgesic activity test to mice
The group number of animals is turned round body number of times analgesia %
Normal saline group 10 20 times 0
10 0 100*** of morphine group
10 7 65** of test group
*: expression P＜0.01
As seen from the experiment, test group medicine and matched group relatively have significant difference.Show that this group medicine and matched group relatively have certain analgesic effect.
Claims (10)
1, contains the sustained release pharmaceutical formulation of breviscapine, it is characterized in that: form by the breviscapine of 5%-95% and the slow-release material of 5%-95%.
2, the pharmaceutical preparation of claim 1, described breviscapine is a scutellarin.
3, the pharmaceutical preparation of claim 2 is tablet, capsule, suspensoid, granule, pill, patch.
4, the pharmaceutical preparation of claim 2, wherein the amount of scutellarin is the 1mg-200mg/ agent.
5, the pharmaceutical preparation of claim 2, slow-release material wherein comprise cellulose family, acroleic acid resin class, stearic acid esters, starch, cyclodextrin, sodium alginate, carbomer, PVP, lactose.
6, the pharmaceutical preparation of claim 2 is made up of scutellarin 1mg-200mg/ agent, hydroxypropyl emthylcellulose 1-200mg/ agent, lactose 1-100mg/ agent, sodium alginate 1-100mg/ agent, carbomer 0.1-10mg/ agent, PVP 0.1-10mg/ agent.
7, the pharmaceutical preparation of claim 6 is grouped into by following one-tenth
Scutellarin 10-60mg/ agent
Hydroxypropyl emthylcellulose (HPMC K15M) 10-60mg/ agent
Lactose 5-30mg/ agent
Sodium alginate 5-40mg/ agent
Carbomer 0.5-2mg/ agent
PVP alcoholic solution 0.5-2mg/ agent
8, the pharmaceutical preparation of claim 7 is grouped into by following one-tenth
Scutellarin 30.0mg/ agent
Hydroxypropyl emthylcellulose (HPMC K15M) 35.5mg/ agent
Lactose 15.0mg/ agent
Sodium alginate 20.0mg/ agent
Carbomer 1.0mg/ agent
PVP alcoholic solution 1.0mg/ agent
9, the pharmaceutical preparation of claim 2 is scutellarin slow-release patchs, is grouped into by following one-tenth
A: drug storehouse layer
Scutellarin 10%
Polyacrylic resin 60%
Ethyl acetate 25%
Lauryl alcohol 5%
B: adhesion layer
Scutellarin 3%
Polyacrylic resin 65%
Ethyl acetate 27%
Lauryl alcohol 5%
10, the pharmaceutical preparation of claim 1 is grouped into by following one-tenth
Scutellarin 10-60mg/ agent
Hydroxypropyl emthylcellulose (HPMC K15M) 10-60mg/ agent
Lactose 5-30mg/ agent
Sodium alginate 5-40mg/ agent
Carbomer 0.5-2mg/ agent
PVP alcoholic solution 0.5-2mg/ agent
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021167958A CN1162158C (en) | 2002-05-15 | 2002-05-15 | Process for preparing novel medicine for breviscapine having function of promoting blood circulation and removing blood stasis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021167958A CN1162158C (en) | 2002-05-15 | 2002-05-15 | Process for preparing novel medicine for breviscapine having function of promoting blood circulation and removing blood stasis |
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| Publication Number | Publication Date |
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| CN1385163A true CN1385163A (en) | 2002-12-18 |
| CN1162158C CN1162158C (en) | 2004-08-18 |
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| Application Number | Title | Priority Date | Filing Date |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110694036A (en) * | 2019-08-21 | 2020-01-17 | 云南中医药大学 | Sanfu plaster with slow release function and preparation method thereof |
-
2002
- 2002-05-15 CN CNB021167958A patent/CN1162158C/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110694036A (en) * | 2019-08-21 | 2020-01-17 | 云南中医药大学 | Sanfu plaster with slow release function and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1162158C (en) | 2004-08-18 |
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Owner name: WU LIANG YE GROUP, YIBIN PHARMACEUTICAL CO.,LTD., Free format text: FORMER OWNER: SICHUAN CHENGDU QINGYANG CHINESE MEDICINE SCIENCE APPLICATION INSTITUTE Effective date: 20080606 |
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Effective date of registration: 20080606 Address after: No. 2, middle Changjiang Road, Sichuan, Yibin Patentee after: Sichuan Yibin Wuliangye Group Yibin Pharmaceutical Co., Ltd. Address before: Sichuan city of Chengdu Province, Chengdu University of Technology archives (three Chengdu Road, two Bridge No. 1) Patentee before: Chengdu Qingyang Chinese Medicine Science and Technology Application Inst., Sich |
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Assignee: Chengdu Libang Biological Pharmaceutical Co Ltd Assignor: Sichuan Yibin Wuliangye Group Yibin Pharmaceutical Co., Ltd. Contract record no.: 2011510000288 Denomination of invention: Process for preparing novel medicine for breviscapine having function of promoting blood circulation and removing blood stasis Granted publication date: 20040818 License type: Exclusive License Open date: 20021218 Record date: 20110916 |
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Address after: 644104 Yibin, Shandong Province, industrial zone, long Luo, Binjiang East Road, No. 1, No. Patentee after: China Pharmaceutical Group Yibin Pharmaceutical Co., Ltd. Address before: 644002 Yibin Changjiang Road, Sichuan, No. 2 Patentee before: Sichuan Yibin Wuliangye Group Yibin Pharmaceutical Co., Ltd. |
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