CN1296060C - Compound ginkgo leaf reparation and its making method - Google Patents
Compound ginkgo leaf reparation and its making method Download PDFInfo
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- CN1296060C CN1296060C CNB2003101239952A CN200310123995A CN1296060C CN 1296060 C CN1296060 C CN 1296060C CN B2003101239952 A CNB2003101239952 A CN B2003101239952A CN 200310123995 A CN200310123995 A CN 200310123995A CN 1296060 C CN1296060 C CN 1296060C
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- extract
- radix ginseng
- folium ginkgo
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- rhizoma chuanxiong
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to a compound ginkgo leaf preparation which is prepared from ginkgo leaf extract, ginseng extract, and chuanxiong rhizome volatile oil or borneol. The preparation can be used for preventing and treating coronary heart disease and angina pectoris, and has fine protecting effect on cerebral ischemia damage. The present invention provides a preparing method and pharmacological effect.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation and preparation method thereof, the present invention relates to a kind of compound gingko leaf preparation and preparation method thereof specifically.
Background technology
Folium Ginkgo is the leaf of Ginkgoaceae Ginkgo plant Ginkgo biloba (Ginkgobiloba L.).Contain flavonoid (kind surplus in the of about 20), terpenoid, phenols, effective ingredient such as healthy trace elements with household and 17 seed amino acids have and reduce serum cholesterol, coronary blood flow increasing, improve cerebral blood circulation, remove smooth muscle spasm, lax bronchus and pharmacological action such as antibacterial.Not only be applied to treat cardiovascular and cerebrovascular disease clinically, and nervous system, respiratory system etc. is also had good effect.Scientist such as France and Germany is verified, and Folium Ginkgo extract is all having significant curative effect aspect treatment cerebral ischemia, brain injury sequela and the defying age.
In recent years, along with people go deep into the further of Semen Ginkgo research, the report that Semen Ginkgo and other medical material compatibilities use day by day increases.[the early stage Fibrotic preliminary study of compound gingko leaf preparation treatment chronic hepatitis B such as Li Wei, China combination of Chinese and Western medicine magazine .1995,15 (10): 593] report, select for use Folium Ginkgo, the Radix Astragali, Radix Scutellariae, Rhizoma Polygoni Cuspidati, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Radix Angelicae Sinensis, Carapax Trionycis etc. to make electuary, the early stage patients with liver fibrosis of treatment chronic type b delay property and active hepatitis, the result shows that the hepatic fibrosis process is eased, and the early stage fibrosis of chronic hepatitis B is all had curative effect preferably.[the development of compound gingkgo pulse invigorating capsule such as Chen Dengfeng, Chinese Hospitals pharmaceutical journal .2000,20 (3): 146-147] report, adopt Folium Ginkgo, Radix Notoginseng, Radix Salviae Miltiorrhizae, the Radix Astragali and Rhizoma Chuanxiong etc. to make the compound gingkgo pulse invigorating capsule, effect with blood circulation promoting and blood stasis dispelling, clinical prevention and the treatment that is used for cardiovascular and cerebrovascular disease obtained good effect.Liu Xiaotian etc. [compound folium ginkgo tincture treatment burn 38 examples are observed Zhejiang combination of Chinese and Western medicine magazine .1998,8 (6): 391] have reported that employing Folium Ginkgo, Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Camphora etc. make tincture, and treatment burn 38 examples have obtained satisfied curative effect.
Above-mentionedly introduce us as can be seen, Semen Ginkgo is as the medicine of an outstanding treatment cardiovascular and cerebrovascular disease, and present compound ginkgo agent report seldom is applied to the just more limited of cerebrovascular disease.
Summary of the invention
In light of this situation, the objective of the invention is to overcome deficiency of the prior art, a kind of reasonable, that technology is strict compound gingko leaf preparation and preparation method thereof of filling a prescription is provided.
Purpose of the present invention is achieved by following technical proposals.
Compound gingko leaf preparation of the present invention is made by Folium Ginkgo, Radix Ginseng and Rhizoma Chuanxiong or Borneolum Syntheticum, and concrete is to extract the active component of Folium Ginkgo, Radix Ginseng and the volatile oil or the Borneolum Syntheticum of Rhizoma Chuanxiong respectively, adds adjuvant, makes preparation.
1. the extraction of Semen Ginkgo extrac (general flavone content is 5～60%, total lactone content 1～30%): get Folium Ginkgo, pulverize or do not pulverize, adopt water extraction, or the organic solvent extraction method, or resin adsorption method, or supercritical fluid extraction, get Folium Ginkgo extract;
2. the extraction of Radix Ginseng extract (total saponin content 40～80%): get Radix Ginseng (or stem, leaf), adopt water extraction, or the organic solvent extraction method, or column adsorption method, Radix Ginseng extract;
3. the extraction of Rhizoma Chuanxiong volatile oil: get Rhizoma Chuanxiong, adopt hydrodistillation, or supercritical fluid extraction, promptly get volatile oil; Or adopt Borneolum Syntheticum to substitute Rhizoma Chuanxiong volatile oil;
4. get Folium Ginkgo extract 30～90%, Radix Ginseng extract 1～30%, Rhizoma Chuanxiong volatile oil 1～50%;
5. or get Folium Ginkgo extract 30～90%, Radix Ginseng extract 1～60%, Borneolum Syntheticum 1～10%;
6. get the Semen Ginkgo extrac and the Radix Ginseng extract of dosage described in step 4 or 5, add suitable dehydrated alcohol it is fully disperseed, mix homogeneously;
7. with said extracted thing and volatile oil or Borneolum Syntheticum mix homogeneously, add adjuvant, make preparation.
The mixing temperature of Semen Ginkgo extrac and Radix Ginseng extract is controlled at below 65 ℃ in the step 6, is preferably 60 ℃, contains the alcohol amount and is controlled at below 5% of accumulated dose, is preferably 4%; In the described step 7, can make any one dosage form on the pharmaceutics, be preferably drop pill; The adjuvant that the preparation drops uses is selected from following a kind of or their combination: Polyethylene Glycol (molecular weight is the mixture of 9000,6000 and 4000 arbitrary proportions), or sodium stearate, or glycerin gelatine, or starch, or dextrin or lactose etc.; It is as follows to drip the system step: the adjuvant heating and melting, join in the scattered mixture, and fully mix, drip and make ball.Temperature is controlled at below 65 ℃, and preferred 60 ℃, wherein, to change in the process of a material and a system, temperature should be controlled at below 65 ℃, is preferably 60 ℃.
Drop pill is meant solid drugs or liquid medicine and the fusion of adjuvant substrate Hybrid Heating, splashes in the immiscible condensing agent, shrinks the preparation that forms.The process of this drop pill is actually the process of solid dispersion being made drop pill.Because its specific surface area is big, and has very strong water solublity, make it easier by collective's dispersion absorption, sublingual administration directly absorbs through vein, has avoided first pass effect.Really reached quick-acting, purpose efficiently.The present invention has adopted modern crafts, and compound gingko leaf preparation is made drop pill, and the quality control method advanced person has improved content of effective and quality control standard, makes it really reach quick-acting, effect efficiently.
Beneficial effect
Experiment one
Below by the method for using embodiment 10 to provide, make compound gingko leaf preparation of the present invention.And its pharmacodynamic experiment set forth, further specify beneficial effect of the present invention.
Pharmacodynamic experiment
Compound gingkgo drop pill of the present invention and Gin Kgo Plus compare, and adopt the local clothes middle cerebral artery that pastes of ferric chloride to cause the focal cerebral ischemia injury model, inquire into the protective effect of the present invention to rat cerebral ischemia.
(1) reagent: compound gingkgo drop pill of the present invention is provided by sky, Tianjin Shi Li group modern Chinese medicine institute; Gin Kgo Plus, Kang Enbei pharmaceutical Co. Ltd in Zhejiang produces, lot number: 000418-2; Red tetrazolium (TTC) is pale yellow powder, Beijing Ma Shi fine chemicals company limited product, lot number: 011102.
(2) animal: the SD rat, male and female have both, body weight 190～240g, the quality certification number: SCXK11-0008, Beijing dimension tonneau China animal technology company limited provides.
(3) method and result: laboratory animal is divided into four groups at random, i.e. Sham-operated control group, MCAT model group, matched group of the present invention (wherein total extract is 40mg/kg), Gin Kgo Plus equivalent group (containing EGB 24mg/kg).The earlier continuous gastric infusion of animal three days, administration every day volume is 5ml/kg, and a daily dose gives at twice.Administration in the 4th day was performed a surgical operation after 90 minutes, and postoperative continues gastric infusion one day (daily dose once gave in the 4th day, the 5th day).Wherein sham operated rats and MCAT model group gavage isometric 0.5%cmc solution.Middle cerebral artery thrombus model (MCAT) rat mould plough is made: the anesthesia of rats by intraperitoneal injection 10% chloral hydrate solution (350mg/kg), right arm reclining is fixed, make a curved incision at paropia and external auditory meatus line mid point, be about 1.5cm, pinch off temporalis and excision expose temporal bone, under stero microscope, with the bone window of dental burr at cheekbone and the work one diameter 2.5mm of the close oral-lateral 1mm place of temporo squamosum joint, the cleaning residue exposes middle cerebral artery (between tractus olfactorius and inferior cerebral vein).Put small pieces plastic sheeting protection blood vessel surrounding tissue.Have the small pieces quantitative filter paper of 50% ferric chloride solution, 10 μ L to apply on this section middle cerebral artery suction, take off filter paper behind the 30min, use the normal saline flushing local organization, layer-by-layer suture steams again and raises.Room temperature is controlled at 26 ℃ of sham operated rats except that not dripping the ferric chloride solution the same model group of all the other operating procedures.Nervous symptoms methods of marking:, carry out behavior and detect to experimental animal 6h and 24h after surgery.Standards of grading: 1. carry the Mus tail and observe forelimb flexing situation, protract, be designated as 0 fen as two forelimb symmetries; As the offside forelimb of performing the operation shoulder flexing, elbow flexing, shoulder inward turning occur or has concurrently, is designated as 1 fen.2. animal is placed on the plane, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and be designated as 0 fen effectively; As operation collateral resistance is descended, be designated as 1 fen.3. animal two forelimbs are put on the wire netting, observed muscular tension.Bilateral muscular tension equity and be 0 minute effectively; Operation offside muscle of anterior limb tension force descends and is designated as 1 fen.4. carry the Mus tail, animal has ceaselessly to operation offside revolver, is designated as 1 fen.According to above standard scoring, full marks are 4 minutes, and mark is high more, and the behavior disorder of animal is serious more.The assay method of cerebral infarction scope: behind the animal via behavior scoring, broken end is got brain.Remove olfactory bulb, cerebellum and low brain stem, remainder is cut into 5 crown below 4.(every 5ml dye liquor contains 4%TTC 1.5ml, 1M K rapidly the brain sheet to be placed the TTC dye liquor
2HPO
4, 0.1ml, all the other adding distil waters are to scale), 37 ℃ of lucifuge temperature were incubated 30 minutes, took out to be placed on the 24h that keeps in Dark Place in 10% formalin.The non-ischemic region in dyed back is a rose, and infarct is a white.White organized carefully to dig down weigh, account for the percentage ratio of full brain weight and Ipsilateral brain weight as the cerebral infarction scope with blocking tissue's weight.Learn paired comparison t check between check employing group by statistics, the results are shown in following table.
| Group | Number of animals | Dosage | Cerebral infarction scope (%) | The nervous symptoms scoring | ||
| It is heavy to account for full brain | It is heavy to account for the Ipsilateral brain | 6h | 24h | |||
| Sham operated rats model group taponin group compound folium ginkgo drop pill | 10 11 10 10 | 24 40 | 0±0 ** 3.97±2.61 1.85±0.51 * 1.75±0.75 * | 0±0 ** 7.50±4.93 3.53±1.13 * 3.39±1.42 * | 0.20±0.42 ** 2.91±0.54 2.10±0.57 ** 1.78±0.83 ** | 0.20±0.42 ** 3.00±0.63 2.00±0.67 ** 1.67±0.71 ** |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01
Conclusion: by the table in as can be seen, of the present invention group can obviously be dwindled cerebral infarction scope (P＜0.01, P＜0.05), and can improve its nervous symptoms of 6 and 24 hours.
Experiment two: the compound gingkgo drop pill is to intending the experimentation of blood stasis due to qi deficiency model mice protective effect
This research adopts 8 ℃ of cold water swimmings with a load attached to the body of mice modeling in 5 minutes to intend clinical syndrome of blood stasis due to qi deficiency, by the breathe change of persistent period and cerebral tissue biochemical indicator of rating model animal broken end, observe the present invention---the resisting oxygen lack of compound gingkgo drop pill, to illustrate the partial action mechanism of medicine.
(1) material:
Animal: healthy ICR mice, the male and female dual-purpose, body weight 21 ± 2g, the quality certification number: SCXK (capital) 2002-0003 is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..
Medicine: be subjected to reagent thing: CO-GBE, the brownish black drop pill is caught confession by sky, Tianjin Shi Li group modern Chinese medicine institute,
Lot number: 20020416.Prepare with 0.5%CMC before the experiment.Positive control drug: Gin Kgo Plus, pharmaceutical Co. Ltd of Kang Enbei group product, every contains the Folium Ginkgo extract is 40mg, people's consumption per day 3-6 sheet/day.Lot number: 010613-2.
Reagent: protein quantification (biuret method), lactic acid (LA), lactic acid dehydrogenase (LDH), Na
+-K
+-ATP enzyme, Ca
2+-Mg
2+-ATP enzyme reagent kit builds up bio-engineering research by Nanjing and provides.Other medicine and reagent are commercially available analytical pure.
Instrument: HZQ-C air bath agitator, Dongming, Harbin City Medical Instruments factory product; The 400R refrigerated centrifuge, German Heraeus product: 722 type spectrophotometers, Shanghai the 3rd analytical tool factory product; AEG-220 type electronic analytical balance, Japanese Shimadzu company product.
(2) grouping and administration:
Laboratory animal is divided into six groups at random, i.e. dosage group (30mg/kg), compound folium ginkgo drop pill small dose group (15mg/kg) in model control group, blank group, Gin Kgo Plus group (40mg/kg), the heavy dose of group of compound folium ginkgo drop pill (60mg/kg), the compound folium ginkgo drop pill.The earlier continuous gastric infusion of animal three days, a daily dose gives at twice, and administration every day volume is 10ml/kg.Administration modeling after 60 minutes in the 4th day (the 4th day once to full-time amount).Wherein model control group and blank group gavage isometric 0.5%cmc solution.
Modelling: the rubber mud ball of sticking one 10% body weight in the about 2.5cm in mouse tail tip place, the cold water swimming of putting into 8 ± 0.5 ℃ was taken out (in the experimentation, room temperature remains at 23 ℃) to be measured after 5 minutes.
Assay method: the breathe mensuration of persistent period of broken end: after taking out in the white cold water of mice, break end rapidly in the ears rear, record was breathed the persistent period as broken end from new head beginning to its a period of time that stops of breathing for the last time.
The mensuration of biochemical indicator: measure broken end and breathe after the persistent period, get brain rapidly on 4 ℃ of ice pans, and remove olfactory bulb, cerebellum and low brain stem, the jin of weighing adds 9 times of pre-cold salines and is prepared into 10% brain homogenate, and is standby.LA content and LDH vigor, Na
+-K
+-ATP enzyme activity, Ca
2+-Mg
2+-ATP enzyme activity determination all builds up the trial issue box explanation of bio-engineering research institute according to Nanjing and operates.
Statistical procedures: data are with the mean+SD statistical disposition.
(3) result:
The compound gingkgo drop pill is to the breathe influence of persistent period of model mice broken end: model control group is compared with the blank group, broken end persistent period of breathing obviously prolongs: three dosage groups of compound gingkgo drop pill are compared with the model group matched group, broken end persistent period of breathing has further and to prolong (P＜0.1), the results are shown in Table 1.
The compound gingkgo drop pill is to the influence of model mice cerebral tissue biochemical indicator: compare with the blank group, the model control group mouse brain organizes LA content obviously to increase, and LDH, Na
+-K
+-ATP enzyme and Ca
2+-Mg
2+-ATP enzyme activity obviously descends (P＜0.01): three dosage of compound gingkgo drop pill all can obviously reverse the change of the above-mentioned unusual biochemical metabolism of animal pattern cerebral tissue, show as and make animal pattern cerebral tissue LDH, Na
+-K
+-ATP enzyme and Ca
2+-Mg
2+-ATP enzyme activity increases, with low its LA content that has raise (P＜0.05, P＜0.01).Compare with TIANBAONING sheet group, three dosage of compound gingkgo drop pill all can obviously reverse the Na of animal pattern cerebral tissue
+-K
+The abnormal change of-ATP enzyme (P＜0.01), middle dosage group can also reverse Ca
2+-Mg
2+Unusual (P＜0.05) of-ATP enzyme the results are shown in Table 2.
Table 1 compound gingkgo drop pill is to intending the breathe influence of persistent period of qi-deficiency type mice broken end
| Group | Number of animals | Dosage (mg/kg) | Breathe the persistent period (s) breaks end |
| Dosage compound gingkgo drop pill heavy dose in the low dose of compound gingkgo drop pill of blank group model matched group TIANBAONING sheet group compound gingkgo drop pill | 15 16 15 15 15 14 | 40 15 30 60 | 16.33±1.84 ** 28.63±4.32 32.20±2.76 * 32.07±3.08 * 32.07±4.04 * 31.86±3.08 * |
Annotate: with the model group contrast,
*P＜0.05,
*P＜0.01.
Table 2 compound gingkgo drop pill is to intending the influence of blood stasis due to qi deficiency model mice cerebral tissue biochemical metabolism
| Group | LA content (mmol/l) | LDH vigor (u/gprot) | Enzyme activity | |
| Na +-K +-ATP | Ca 2+-Mg 2+-ATP | |||
| Dosage compound gingkgo heavy dose in the low dose of compound gingkgo of blank group model matched group TIANBAONING sheet group compound gingkgo | 1.71±0.46 ** 2.12±0.26 1.45±0.23 ** 1.65±0.16 ** 1.72±0.17 ** 1.79±0.09 ** | 1279.92±295.81 ** 778.41±127.46 ** 903.91±197.95 * 1167.66±274.63 ** 1196.71±614.02 * 983.66±246.81 * | 1.73±0.56 * 0.60±0.38 1.05±0.19 ** 1.74±0.40 **△△ 1.89±0.64 **△△ 2.31±0.53 **△△ | 0.80±0.13 ** 0.51±0.09 0.89±0.17 ** 0.98±0.27 ** 1.04±0.20 **△ 0.90±0.22 ** |
Annotate: number of animals and dosage design contrast with model group with table 1,
*P＜0.05,
*P＜0.01; With the contrast of TIANBAONING sheet group,
△P＜0.05,
△ △P＜0.01.
(4) conclusion:
This experiment finds to intend blood stasis due to qi deficiency model mice cerebral tissue LDH, Na
+-K
+-ATP enzyme and Ca
2+-Mg
2+-ATP enzyme activity all obviously descends, and LA content obviously increases.Give with the compound gingkgo drop pill after can obviously reverse the change of these biochemical indicators.The main component of compound gingkgo drop pill is Folium Ginkgo extract (GBE) and stem and leaf of Radix Ginseng saponin etc.Studies show that prevention gives GBE can effectively suppress the ATP, the reduction of glucose level and the rising of lactate level that occur behind the energy metabolism impairment that micro-embolization causes; The ginsenoside has the inhibition ischemia and irritates LDH activity decline in the cerebral tissue again, delays the exhaustion of ATP in the anaerobic phase cell, improves the effect of energy charge, and can reduce the blood lactic acid concn when moving, the energy balance when moving by changing, generation antifatigue effect.From this result of study as can be seen; several composition synergism in the compound gingkgo drop pill; by opposing acidosis ability that strengthens model mice and lactic acid dehydrogenase, the ATP enzyme activity that raises its reduction; improve the functional status of neuron plasma membrane; alleviate the multiple pathologic-physiological reaction that acidosis brings out, from the effect of a plurality of link performance protection cerebral tissue.
Experiment three
Below by the method for using embodiment 11 to provide, make compound gingko leaf preparation of the present invention.And its pharmacodynamic experiment set forth, further specify beneficial effect of the present invention.
Pharmacodynamics test
Compound gingkgo drop pill of the present invention and Gin Kgo Plus compare, and adopt the local clothes middle cerebral artery that pastes of ferric chloride to cause the focal cerebral ischemia injury model, inquire into the protective effect of the present invention to rat cerebral ischemia.
1. experiment material
1.1 animal
The SD rat, the male and female dual-purpose, body weight 220 ± 10g, the quality certification number: SCXK11-00-0008 is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..
1.2 medicine and reagent
Be subjected to reagent: the compound gingkgo drop pill is the brownish black drop pill, and Shi Li group provides by the sky, Tianjin, lot number: 20020110, prepare with 0.5%CMC before the experiment.Positive control drug: Gin Kgo Plus, pharmaceutical Co. Ltd of Kang Enbei group product, lot number: 000418-2.Red tetrazolium (TTC): be pale yellow powder, Beijing Ma Shi fine chemicals company limited product, lot number: 011102.
1.3 instrument
The XTT stero microscope, Yunnan Optical Instruments Factory's product.
The AEG-220 electronic analytical balance, Japanese Shimadzu company product.
Shanghai Dental Medical Apparatus and Instrument Factory of the desk-top dentistry of 307-6 depot product.
2. experimental technique
2.1 grouping and administration: laboratory animal is divided into five groups at random, promptly Sham-operated control group, MCAT model group, compound gingkgo drop pill A group (wherein containing total effective ingredient amount is 36mg/kg), compound gingkgo drop pill B organize (wherein containing total effective ingredient amount is 30mg/kg), Gin Kgo Plus equivalent group (containing EGB 24mg/kg).The earlier continuous gastric infusion of animal three days, administration every day volume is 5ml/kg, and a daily dose gives at twice.Administration in the 4th day was performed a surgical operation after 90 minutes, and postoperative continues gastric infusion one day (daily dose once gave in the 4th day, the 5th day).Wherein sham operated rats and MCAT model group gavage the Polyethylene Glycol-0.5%cmc solution of equivalent.
2.2 middle cerebral artery thrombus model (MCAT) rat model is made: the anesthesia of rats by intraperitoneal injection 10% chloral hydrate solution (300mg/kg).Press the method for Tamura etc., improve a little.The rat right arm reclining is fixed, make a curved incision at paropia and external auditory meatus line mid point, be about 1.5cm, pinch off temporalis and excision, expose temporal bone, under stero microscope, make the bone window of a diameter 2.5mm near oral-lateral 1mm place at cheekbone and temporo squamosum joint with dental burr, the cleaning residue exposes middle cerebral artery (between tractus olfactorius and inferior cerebral vein).Put small pieces plastic sheeting protection blood vessel surrounding tissue.Have the small pieces quantitative filter paper of 50% ferric chloride solution, 10 μ L to apply on this section middle cerebral artery suction, take off filter paper behind the 30min, use the normal saline flushing local organization, layer-by-layer suture steams again and raises.Room temperature is controlled at 27 ℃.Sham operated rats is except that not dripping the ferric chloride solution the same model group of all the other operating procedures.
2.3 nervous symptoms methods of marking: to experimental animal 6h and 24h after surgery, carry out behavior and detect, improved by the method for Bederson etc.Standards of grading: 1. carry the Mus tail and observe forelimb flexing situation, protract, be designated as 0 fen as two forelimb symmetries; As the offside forelimb of performing the operation shoulder flexing, elbow flexing, shoulder inward turning occur or has concurrently, is designated as 1 fen.2. animal is placed on the plane, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and be designated as 0 fen effectively; As operation collateral resistance is descended, be designated as 1 fen.3. animal two forelimbs are put on the wire netting, observed muscular tension.Bilateral muscular tension equity and be 0 minute effectively: operation offside muscle of anterior limb tension force descends and is designated as 1 fen.4. carry the Mus tail, animal has ceaselessly to operation offside revolver, is designated as 1 fen.According to above standard scoring, full marks are 4 minutes, and mark is high more, and the behavior disorder of animal is serious more.
2.4 the assay method of cerebral infarction scope: behind the animal via behavior scoring, broken end is got brain.Remove olfactory bulb, cerebellum and low brain stem, remainder is cut into 5 crown below 4 ℃.(every 5ml dye liquor contains 4%TTC1.5ml, 1M K rapidly the brain sheet to be placed the TTC dye liquor
2HPO
40.1ml all the other adding distil waters are to scale), 37 ℃ of lucifuge temperature were incubated 30 minutes, took out to be placed on the 24h that keeps in Dark Place in 10% formalin.The non-ischemic region in dyed back is a rose, and infarct is a white.White organized carefully to dig down weigh, account for the percentage ratio of full brain weight and Ipsilateral brain weight as the cerebral infarction scope with blocking tissue's weight.Paired comparison t check the results are shown in following table 3 between statistical test employing group
Table 3 compound gingkgo drop pill is to the influence of cerebral infarction
| Group | Number of animals | Dosage | Cerebral infarction scope (%) | The nervous symptoms scoring | ||
| It is heavy to account for full brain | It is heavy to account for the Ipsilateral brain | 6h | 24h | |||
| Sham operated rats model group taponin group compound folium ginkgo drop pill A | 12 11 10 12 | 24 36 | 0±0 ** 4.16±1.32 △△ 2.66±1.78 * 2.45±1.48 ** | 0±0 ** 8.12±2.61 △△ 5.19±3.35 * 4.75±2.93 ** | 0±0 ** 2.64±0.92 △△ 1.80±0.79 * 1.82±0.75 * | 0±0 ** 2.55±0.52 △△ 1.50±0.53 ** 1.55±0.69 ** |
| Leaf drop pill A compound folium ginkgo drop pill B | 12 | 30 | 1.66±0.73 ** | 3.18±1.41 ** | 1.91±0.54 * | 1.45±0.69 ** |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01; With the sham operated rats contrast,
△ △P＜0.01.
2. brief summary: as can be seen from the table, compound gingkgo drop pill A, B group all can obviously be dwindled the cerebral infarction scope (P＜0.01) of animal pattern, and can improve the nervous symptoms of its 6 hours and 24 hours.
Experiment four
Below by the method for using embodiment 11 to provide, make compound gingko leaf preparation of the present invention.And its pharmacodynamic experiment set forth, further specify beneficial effect of the present invention.
Pharmacodynamics test
1. experiment material
1.1 animal
The ICR mice, the male and female dual-purpose, body weight 21 ± 2g, the quality certification number: SCXK11-00-0008 is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..
1.2 medicine and reagent
1.2.1 be subjected to reagent
Compound gingkgo drop pill A, B, Shi Li group provides lot number for sky, brownish black drop pill Tianjin: prepare with 0.5%CMC before 20020110 experiments.Compound gingkgo drop pill A, clinical people's consumption per day is 252mg; Compound gingkgo drop pill B, clinical people's consumption per day is 312mg.
1.2.2 positive control drug
Gin Kgo Plus, pharmaceutical Co. Ltd of Kang Enbei group product, lot number: 000418-2.The Ginseng Bolus for Tonification, Tongrentang Pharmaceutical Factory, Beijing's product, lot number: 0019972-40.
2. experimental technique
2.1 grouping and administration: laboratory animal is divided into five groups at random, i.e. model control group, compound gingkgo drop pill A group (dosage is 40mg/kg for containing total effective ingredient amount), compound gingkgo drop pill B group (dosage is 50mg/kg for containing total effective ingredient amount), Gin Kgo Plus equivalent group (dosage is for containing EGB 40mg/kg), Ginseng Bolus for Tonification's equivalent group (dosage is 3g/kg).The earlier continuous gastric infusion of animal three days, each administration volume is 2ml/100g, and a daily dose gives at twice.Administration in the 4th day bear a heavy burden after 60 minutes (10% body weight) swimming (daily dose once gave in the 4th day).Wherein model control group gavages the 0.5%cmc solution of equivalent.
2.2 experimental technique: the about 2cm in mouse tail tip place is the rubber mud ball of one 10% body weight, puts into 8 ℃ ± 0.5 ℃ frozen water and swims, and one every barrel, room temperature remains at 23 ℃.Observe mice from putting into water to dead this section period.If surpass 16 minutes, then in 16 minutes.Paired comparison t check the results are shown in following table 4 between statistical test employing group.
Table 4 compound gingkgo drop pill is to the mice influence of swimming death time
| Group | Number of animals | Dosage (g or/kg) | The swimming death time (second) |
| Model group Ginseng Bolus for Tonification organizes Gin Kgo Plus group compound folium ginkgo drop pill group A compound folium ginkgo drop pill group B | 17 16 16 16 15 | 3 40 40 50 | 534.59±125.59 663.38±172.36* 715.75±161.20** 643.81±126.55* 717.27±149.55** |
3. brief summary:
As can be seen from the table, compound gingkgo drop pill A, B group all can obviously prolong the swimming of mice frozen water to the dead time (P＜0.05, P＜0.01).
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
(1) preparation of Folium Ginkgo extract: get the 1000g Folium Ginkgo and pulverize, measure acetone with 5 times: water (70: 30) mixed liquor heating extraction 2 times, each 2 hours, temperature was 50～60 ℃, and merge extractive liquid, filters, and concentrating under reduced pressure becomes Folium Ginkgo extract 280g;
(2) preparation of Radix Ginseng extract: get Radix Ginseng section 100g, add 8 times of water gagings, extract 2 times, each 3 hours, merge extractive liquid, concentrated, and is concentrated into every 5ml and contains the 1g ginseng crude drug, gets Radix Ginseng extract 40g;
(3) get Rhizoma Chuanxiong, pulverize, adopt hydrodistillation, get Rhizoma Chuanxiong volatile oil 80g;
(4) get above-mentioned Semen Ginkgo extrac and Radix Ginseng extract, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(5) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil mix homogeneously, add polyethylene glycol 6000, at 60 ℃ of followingization material, drip and make drop pill.
Embodiment 2
(1) preparation of Folium Ginkgo extract: get Folium Ginkgo and pulverize, add 5 times of amount 65% alcohol reflux 2 times, each 2 hours, temperature was 60 ℃, and merge extractive liquid, filters, and concentrating under reduced pressure reclaims ethanol and gets Folium Ginkgo extract 280g;
(2) preparation of Radix Ginseng extract: get the Radix Ginseng section, add 8 times of amount 70% ethanol, extract 2 times, each 3 hours, merge extractive liquid, reclaimed ethanol, is concentrated into every 5ml and contains the 1g ginseng crude drug, gets Radix Ginseng extract 40g;
(4) get Rhizoma Chuanxiong, pulverize, adopt hydrodistillation, get Rhizoma Chuanxiong volatile oil 80g;
(5) get above-mentioned Semen Ginkgo extrac and Radix Ginseng extract, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(6) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil mix homogeneously, add Polyethylene Glycol 9000, at 60 ℃ of followingization material, drip and make drop pill.
Embodiment 3
(1) with Folium Ginkgo extract 340g, Radix Ginseng extract 20g and Rhizoma Chuanxiong volatile oil 40g mix homogeneously, makes drop pill.
(2) get Rhizoma Chuanxiong, pulverize, adopt supercritical extraction, get Rhizoma Chuanxiong volatile oil 40g;
(3) get Folium Ginkgo extract and Radix Ginseng extract method for making with embodiment 2.
Wherein, Semen Ginkgo extrac in the step 1 and Radix Ginseng extract add dehydrated alcohol, and it is fully disperseed, mix homogeneously, and temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose; With Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil mix homogeneously, add polyethylene glycol 6000, at 60 ℃ of followingization material, drip and make drop pill.
Embodiment 4
(1) preparation of Folium Ginkgo extract: get Folium Ginkgo, add 5 times of amount 65% ethanol, heating and refluxing extraction 2 times, each 1 hour, 60 ℃ of temperature, merge extractive liquid, concentrates, and it is refining to cross macroporous adsorbent resin (D101), use 85% ethanol elution, eluent concentrates and reclaims ethanol, gets Folium Ginkgo extract 340g;
(2) preparation of Radix Ginseng extract: get Radix Ginseng, ethanol, heating and refluxing extraction 3 times, each 1 hour, merge extractive liquid, concentrated, it is refining to cross neutral alumina, use pure eluting, eluent concentrates and reclaims ethanol, Folium Ginkgo extract, get Radix Ginseng extract 20g;
(3) get above-mentioned Semen Ginkgo extrac and Radix Ginseng extract, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 56 ℃, contains the alcohol amount and is controlled at 3% of accumulated dose;
(4) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil 40g mix homogeneously, add polyethylene glycol 6000, at 59 ℃ of followingization material, drip and make drop pill.
(5) the Rhizoma Chuanxiong volatile oil method for making is with embodiment 3.
Embodiment 5
(1) preparation of Folium Ginkgo extract: get the pulverizing Folium Ginkgo, adopt CO
2Supercritical extraction gets Folium Ginkgo extract 200g, and process conditions are that temperature is 45 ℃, and extracting pressure is 25Mpa, flow 0.8ml/min, 2 hours time.Wherein Ginkgo total flavones 50%, terpene lactones 15%;
(2) get above-mentioned Semen Ginkgo extrac and Radix Ginseng extract, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(3) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil 120g mix homogeneously, add Polyethylene Glycol 9000, at 60 ℃ of followingization material, drip and make drop pill.
(4) the Radix Ginseng extract method for making is with embodiment 4;
(5) method for making of Rhizoma Chuanxiong volatile oil is with embodiment 3.
Embodiment 6
(1) get above-mentioned Semen Ginkgo extrac 200g and Radix Ginseng extract 80g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 59 ℃, contains the alcohol amount and is controlled at 5% of accumulated dose;
(2) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil 120g mix homogeneously, add Polyethylene Glycol 9000, at 60 ℃ of followingization material, drip and make drop pill.
(3) the Folium Ginkgo extract method for making is with embodiment 5;
(4) extract of Radix Ginseng leaf method for making embodiment 1;
(5) the Rhizoma Chuanxiong volatile oil method for making is with embodiment 3.
Embodiment 7
(1) get above-mentioned Semen Ginkgo extrac 140g and Radix Ginseng extract 100g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(2) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil 160g mix homogeneously, add Polyethylene Glycol 9000, at 60 ℃ of followingization material, drip and make drop pill.
(3) the Folium Ginkgo extract method for making is with embodiment 2;
(4) preparation of Radix Ginseng extract is with embodiment 4;
(5) the Rhizoma Chuanxiong volatile oil preparation is with embodiment 3.
Embodiment 8
(1) get above-mentioned Semen Ginkgo extrac 140g and Radix Ginseng extract 100g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(2) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil 160g mix homogeneously, add Polyethylene Glycol 9000, at 60 ℃ of followingization material, drip and make drop pill.
(3) the Folium Ginkgo extract preparation is with embodiment 4;
(4) the preparation embodiment 4 of Radix Ginseng extract;
(5) preparation of Rhizoma Chuanxiong volatile oil is with embodiment 3.
Embodiment 9
(1) get above-mentioned Semen Ginkgo extrac 240g and Radix Ginseng extract 60g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(2) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil 100g mix homogeneously, add sodium stearate, 58 ℃ of blankings, drip and make drop pill.
(3) the Folium Ginkgo extract preparation is with embodiment 5;
(4) the Radix Ginseng extract preparation is with embodiment 4;
(5) the Rhizoma Chuanxiong volatile oil preparation is with embodiment 3.
Embodiment 10
(1) get above-mentioned Semen Ginkgo extrac 240g and Radix Ginseng extract 60g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(2) with Folium Ginkgo, Radix Ginseng extract and Rhizoma Chuanxiong volatile oil 100g mix homogeneously, add glycerin gelatine, at 58 ℃ of followingization material, drip and make drop pill.
(3) the Folium Ginkgo extract preparation is with embodiment 4;
(4) the Radix Ginseng extract preparation is with embodiment 4;
(5) the Rhizoma Chuanxiong volatile oil preparation is with embodiment 3.
Embodiment 11
(1) get Borneolum Syntheticum 16g and pulverize, standby;
(2) get above-mentioned Semen Ginkgo extrac 256g and Radix Ginseng extract 128g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 58 ℃, contains the alcohol amount and is controlled at 5% of accumulated dose;
(3) with Folium Ginkgo, Radix Ginseng extract and Borneolum Syntheticum mix homogeneously, add polyethylene glycol 6000, at 60 ℃ of followingization material, drip and make drop pill.
(4) the Folium Ginkgo extract preparation is with embodiment 4;
(5) preparation of Radix Ginseng extract is with embodiment 4.
Embodiment 12
(1) get Borneolum Syntheticum 12g and pulverize, standby;
(2) get above-mentioned Semen Ginkgo extrac 312g and Radix Ginseng extract 76g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(3) with Folium Ginkgo, Radix Ginseng extract and Borneolum Syntheticum mix homogeneously, add polyethylene glycol 6000, at 60 ℃ of followingization material, drip and make drop pill.
(4) the Folium Ginkgo extract preparation is with embodiment 2;
(5) preparation of Radix Ginseng extract is with embodiment 2.
Embodiment 13
(1) get Borneolum Syntheticum 12g and pulverize, standby;
(2) get above-mentioned Semen Ginkgo extrac 200g and Radix Ginseng extract 188g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(3) with Folium Ginkgo, Radix Ginseng extract and Borneolum Syntheticum mix homogeneously, add sodium stearate, at 60 ℃ of followingization material, drip and make drop pill.
(4) the Folium Ginkgo extract preparation is with embodiment 3;
(5) preparation of Radix Ginseng extract is with embodiment 3.
Embodiment 14
(1) get Borneolum Syntheticum 16g and pulverize, standby;
(2) get above-mentioned Semen Ginkgo extrac 280g and Radix Ginseng extract 104g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(3) with Folium Ginkgo, Radix Ginseng extract and Borneolum Syntheticum mix homogeneously, add glycerin gelatine, at 60 ℃ of followingization material, drip and make drop pill.
(4) the Folium Ginkgo extract preparation is with embodiment 4;
(5) preparation of Radix Ginseng extract is with embodiment 4.
Embodiment 15
(1) get Borneolum Syntheticum 12g and pulverize, standby;
(2) get above-mentioned Semen Ginkgo extrac 160g and Radix Ginseng extract 228g, add dehydrated alcohol, it is fully disperseed, mix homogeneously, temperature is controlled at 60 ℃, contains the alcohol amount and is controlled at 4% of accumulated dose;
(3) with Folium Ginkgo, Radix Ginseng extract and Borneolum Syntheticum mix homogeneously, add polyethylene glycol 6000, at 60 ℃ of followingization material, drip and make drop pill.
(4) the Folium Ginkgo extract preparation is with embodiment 5;
(5) preparation of Radix Ginseng extract is with embodiment 5.
Claims (5)
1. compound gingko leaf preparation, it is characterized in that it is made of following component by weight percentage: Folium Ginkgo extract 30-90%, Radix Ginseng extract 1-30%, Rhizoma Chuanxiong volatile oil 1-50%, wherein each extract adopts following method to be prepared from: Folium Ginkgo extract: get Folium Ginkgo, pulverize, adopt ethanol extraction, extracting solution is crossed resin absorption, ethanol elution is collected eluent, concentrates recovery ethanol and gets Folium Ginkgo extract;
Radix Ginseng extract: get Radix Ginseng, adopt the organic solvent extraction method to get Radix Ginseng extract;
Rhizoma Chuanxiong volatile oil: get Rhizoma Chuanxiong, adopt steam distillation to get Rhizoma Chuanxiong volatile oil.
2. a kind of compound ginkgo agent according to claim 1 is characterized in that, described each components contents is: Folium Ginkgo extract 40-80%, Radix Ginseng extract 5-25%, Rhizoma Chuanxiong volatile oil 10-40%.
3. a kind of compound ginkgo agent according to claim 1 is characterized in that, described each components contents is: Folium Ginkgo extract 60%, Radix Ginseng extract 15%, Rhizoma Chuanxiong volatile oil 25%.
4. a kind of compound ginkgo agent according to claim 1 is characterized in that, general flavone content is 560% in the described Folium Ginkgo extract, and total lactone content is 1-30%.
5. a kind of compound ginkgo agent according to claim 1 is characterized in that, total saponin content is 40-80% in the described Radix Ginseng extract.
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| CNB2003101239952A CN1296060C (en) | 2002-05-14 | 2003-12-25 | Compound ginkgo leaf reparation and its making method |
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| CN02117729.5 | 2002-05-14 | ||
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| CNB2003101239952A CN1296060C (en) | 2002-05-14 | 2003-12-25 | Compound ginkgo leaf reparation and its making method |
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| CN2006101376722A Division CN101099758B (en) | 2003-12-25 | 2003-12-25 | Compound gingko leaves preparation and its preparing process |
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| CN1296060C true CN1296060C (en) | 2007-01-24 |
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| CN100346797C (en) * | 2004-11-26 | 2007-11-07 | 秦引林 | Compound injection from ice tablet and ginkgo leaf extract and its making method thereof |
| CN1872111B (en) * | 2005-06-01 | 2010-09-29 | 天津天士力制药股份有限公司 | Medication for treating cardiovascular diseases and cerebrovascular disease |
| CN103340910B (en) * | 2013-07-26 | 2014-06-11 | 周笑同 | Traditional Chinese medicine composition capable of refreshing and restoring consciousness and preventing cold and application of traditional Chinese medicine composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1107349A (en) * | 1994-10-10 | 1995-08-30 | 万县市制药厂 | Ginkgo preparation for treatment of heart disease |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1107349A (en) * | 1994-10-10 | 1995-08-30 | 万县市制药厂 | Ginkgo preparation for treatment of heart disease |
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