CN1210048C - Gingko leaf drop pill - Google Patents
Gingko leaf drop pill Download PDFInfo
- Publication number
- CN1210048C CN1210048C CN02131267.2A CN02131267A CN1210048C CN 1210048 C CN1210048 C CN 1210048C CN 02131267 A CN02131267 A CN 02131267A CN 1210048 C CN1210048 C CN 1210048C
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- China
- Prior art keywords
- folium ginkgo
- extract
- macrogol
- polyethylene glycol
- ginkgo extract
- Prior art date
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- Expired - Lifetime
Links
- 239000006187 pill Substances 0.000 title claims abstract description 74
- 244000194101 Ginkgo biloba Species 0.000 title abstract description 195
- ZDXLFJGIPWQALB-UHFFFAOYSA-M disodium;oxido(oxo)borane;chlorate Chemical compound [Na+].[Na+].[O-]B=O.[O-]Cl(=O)=O ZDXLFJGIPWQALB-UHFFFAOYSA-M 0.000 title abstract 2
- 235000008100 Ginkgo biloba Nutrition 0.000 claims abstract description 218
- 235000011201 Ginkgo Nutrition 0.000 claims abstract description 213
- 238000002360 preparation method Methods 0.000 claims abstract description 98
- 241000208340 Araliaceae Species 0.000 claims abstract description 6
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims abstract description 6
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- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 22
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 21
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- YXHVCZZLWZYHSA-FPLPWBNLSA-N Ginkgoic acid Chemical compound CCCCCC\C=C/CCCCCCCC1=CC=CC(O)=C1C(O)=O YXHVCZZLWZYHSA-FPLPWBNLSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
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- XRRONFCBYFZWTM-UHFFFAOYSA-N octadecanoic acid;sodium Chemical compound [Na].CCCCCCCCCCCCCCCCCC(O)=O XRRONFCBYFZWTM-UHFFFAOYSA-N 0.000 description 2
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- YPYPBEGIASEWKA-UHFFFAOYSA-N 5-phenyl-1,3-oxazole Chemical compound O1C=NC=C1C1=CC=CC=C1 YPYPBEGIASEWKA-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to a ginkgo leaf drop pill preparation which is composed of ginkgo leaf extract, medicinal auxiliary material and auxiliary components comprising astragalus root, ginseng, atractylodes macrocephala, etc. The present invention not only can be used for protecting vascular endothelium injury and reducing cholesteryl, but also has great protective effect on cerebral ischemia injury. The present invention provides a preparation method and pharmacologic action.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation and preparation method thereof, more particularly the present invention relates to a kind of folium ginkgo dripping pill preparation.
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, be the health food and the fashionable world of cosmetics that raw material is made with the Folium Ginkgo, only European annual value of production exceedes 5,000,000,000 dollars.Ginkgo is the special product plant of China, and aboundresources accounts for about 70% of world's total amount, and deeply exploitation has vast market prospect.
The chemical constituent of Folium Ginkgo is comparatively complicated, has found 100 number of chemical compositions up to now from Folium Ginkgo, and flavone compound, terpene lactone, polyisoamylene alcohols are wherein arranged, and also has organic acid, alkyl phenol and steroid compound etc. in addition.Ketone compounds, terpene lactone, polyisoamylene alcohols are considered to main active, and ginkgoic acid is considered to main toxic component.Since the sixties in last century, domestic and international many scholars have done a large amount of further investigations to chemical constituent and the extraction process thereof of Semen Ginkgo, have become " focus " problem of plant pharmacological research in the world at present.The main extracting method that adopts is as follows:
Water or organic solvent extraction method
The method is domestic and international the most widely used method.Widely used solvent system has alcohol-water (60～70%) or acetone-water solution (50～60%) to carry out lixiviate.Now concrete operation method is summarized as follows:
Ethanol extraction method: dry Folium Ginkgo is pulverized, be immersed in the ethanol,, concentrate and reclaim ethanol, get Folium Ginkgo extract 60 ℃ of reflux; The acetone extraction method: Folium Ginkgo is pulverized, handled about 5h at about 55 ℃ with 60% aqueous acetone solution, cold filtration, filtrate is used CCl
4Extract 3 times, reclaim under reduced pressure acetone gets Folium Ginkgo extract; Water extraction method: dry Folium Ginkgo is pulverized, used water extraction 3h, filter, precipitate with ethanol concentrates and reclaims ethanol, gets Folium Ginkgo extract.
Water or organic solvent extraction add macropore resin purification method
Because flavone compound and lactone compound less (being respectively about 1.7% and 0.6%) during employing above-mentioned " water or organic solvent extraction method " is extract obtained, therefore must be by the further separation and purification of the extractum that this kind method obtains, the method of purification is a lot, and wherein commonly used is exactly to adopt macroporous adsorbent resin to make with extra care.Hu Min etc. [Wuhan University's journal (natural science edition), 1998,44 (2): 255] have inquired into the principle that solvent extraction and resin adsorption method are made with extra care Folium Ginkgo flavone, and the result shows that the resin absorption process for purification is better than the solvent extraction method for refining.In recent years, mainly the resin that uses is non-polar macroporous resin, as resins such as HP-20, XAD-4, D101.Adopting the main feature of resin adsorption method is that cost is low, the response rate is high, and organic solvent residual is few.
Supercritical extraction method (SFE method)
The SFE method is the novel method of active component in the separating plant of rising in recent years.It mainly can realize optionally extract and separate, purification by the adding etc. of control temperature, pressure and this property agent.Deng Qizhang etc. [Chinese herbal medicine, 1999,30 (6): 419] have set up a cover supercritical fluid lab scale, pilot-plant and test method, and resulting Folium Ginkgo extract flavones content is 28%, and bilobalide content is 7.2%, all is higher than internationally recognized standard.Compare with organic solvent, have extraction ratio height, no solvent residue, active component and thermally labile component and be difficult for advantages such as destroyed.
The high speed adverse current chromatogram extraction method (High Speed Counter Current Chromatography, HSCCC)
The high speed adverse current chromatogram extraction method is a kind of liquid luquid partition chromatography technology that need not any immobilization carrier.Cai Dingguo etc. [new Chinese medicine and clinical pharmacology, 1999,10 (1): 44] report adopts the HSCCC technology, separates to have obtained 3 kinds of main glycoside units from Folium Ginkgo.The method has separation rate height to sample, products obtained therefrom concentration height, advantage such as pollution-free, is the preferable means of preparation ginkgo flavonoid glycoside and each bilobalide and bilobalide reference substance.
Enzyme process
At the contained liposoluble constituent of Folium Ginkgo or be insoluble in the effective ingredient of water, by adding the starch partial hydrolysate glucosyl group residue there are the glucosidase or the transglycosylase of transferance, make fat-soluble or slightly solubility composition or water-fast effective ingredient are transferred in the water-soluble sugar.[Chinese patent medicine such as Li Zhaolong, 1994,16 (10): 52] reported that Japanese height reaches the Gluconase that glucose residue there be transferance with the method by the adding dextrin with the virtue spring, regulated PH2.0, temperature is changeed the sugar reaction for 50 ℃, the effective ingredient that makes the oil-soluble composition and be insoluble in water is transformed into glucoside soluble in water and extracts, heat up then, make enzyme deactivation, supernatant is crossed the HP-20 macroporous adsorbent resin, collect filtrate, be drying to obtain.The active constituent content height that inferior method is extracted, and very easily absorb after changing into glucoside in vivo.
At present, " Chinese pharmacopoeia (2000 editions enlarged editions) has been stipulated the quality standard of Folium Ginkgo extract (GBE), and promptly total flavonoid of ginkgo must not be less than 24%, and bilobalide must not be less than 6%.
In recent years, along with people to the going deep into of Folium Ginkgo research, now developed oral liquid, tablet, capsule and electuary at interior a series of preparations.Because dosage form itself, they exist problem: 1. solid orally ingestible (as tablet, capsule etc.) disintegration rate is slow, and the effective ingredient rate of release is low.The disintegrate of solid orally ingestible is the prerequisite of its stripping, and disintegration time is long more, and then the dissolution rate of its effective ingredient is slow more." Chinese Pharmacopoeia 2000 editions " stipulated tablet, the capsule disintegration time should be within an hour.So Chang time for the rapid release of effective ingredient beyond doubt without any helping.2. first pass effect problem.First pass effect (First-pass Effect) claim the first pass effect again, is meant oral drugs after gastrointestinal absorption, at first arrives liver through portal vein, enters the body circulation again.By metabolism, this phenomenon becomes first pass effect to some medicine by liver the time.Oral formulations is because itself, and major part absorbs in gastrointestinal tract, is easy to generate first pass effect, and its effective ingredient is reduced.At the problem of above existence, we need a kind of quick-acting, gingko leaf preparation satisfies the needs of clinical practice efficiently.
Summary of the invention
At the deficiencies in the prior art, the invention provides a kind of efficient, quick-acting folium ginkgo dripping pill preparation, the present invention is also unexpected to be found, said preparation has significant good result than existing preparation aspect the treatment cerebral infarction.
Purpose of the present invention is achieved by following scheme.
A kind of folium ginkgo dripping pill of the present invention, wherein the ratio of Folium Ginkgo extract and adjuvant is 1: 1.5～10.
Described each components contents is preferably: the ratio of Folium Ginkgo extract and adjuvant is 1: 2～4,
Described each components contents is preferably: the ratio of Folium Ginkgo extract and adjuvant is 1: 3.
The present invention also contains other medicinal or inactive ingredients except that containing above-mentioned Folium Ginkgo extract and adjuvant, no matter it uses separately still that its content of combination in any between them all is no more than 10% of Semen Ginkgo extrac weight.The above adjuvant is specially Macrogol 4000, polyethylene glycol 6000 or Macrogol 4000,6000 mixture or other suitable Polyethylene Glycol and their mixture, perhaps glycerin gelatine or the stearic acid sodium etc. of molecular weight between 2000 to 10000 of making drop pill.
Following steps are taked in the preparation of a kind of folium ginkgo dripping pill of the present invention:
1. be ready to following raw material: Folium Ginkgo extract, adjuvant and other medicinal and inactive ingredients;
2. with the above-mentioned raw materials mix homogeneously;
3. add the transconversion into heat material, move into the drip irrigation of drop pill machine, medicinal liquid splashes in the liquid sub liquid paraffin by water dropper, removes liquid paraffin, selects ball, promptly.
The 1. described adjuvant of step comprises Macrogol 4000, polyethylene glycol 6000 or Macrogol 4000,6000 mixture or glycerin gelatine or stearic acid sodium, and wherein the ratio of Macrogol 4000,6000 mixture is 1: 0.01～99.9.
Described medicinal component is the extract of medicines such as the Radix Astragali, Radix Ginseng, the Rhizoma Atractylodis Macrocephalae, Poria, Fructus Schisandrae Chinensis, the Radix Paeoniae Alba, Radix Salviae Miltiorrhizae, Radix Notoginseng, and their preparation method is summarized as follows:
Radix Astragali extract: get the Radix Astragali, pulverize, extracting in water, precipitate with ethanol concentrates and reclaims alcohol, gets Radix Astragali extract;
Radix Ginseng extract: get Radix Ginseng, pulverize, add alcohol reflux, cross macroporous adsorbent resin, use pure eluting, collect eluent, concentrate and remove alcohol, get Radix Ginseng extract.
Rhizoma Atractylodis Macrocephalae extract: get the Rhizoma Atractylodis Macrocephalae, pulverize, extracting in water filters, concentrate Rhizoma Atractylodis Macrocephalae extract.
Poria extract: get Poria, extracting in water filters, and concentrates, and precipitate with ethanol reclaims the pure extract that gets.
Fructus Schisandrae Chinensis extrat: get Fructus Schisandrae Chinensis, add alcohol reflux and extract, filter, concentrate and reclaim the pure extract that gets.
Radix Paeoniae Alba extract: get the Radix Paeoniae Alba, extracting in water filters, precipitate with ethanol, concentrate Radix Paeoniae Alba extract.
Radix Salviae Miltiorrhizae extract: get Radix Salviae Miltiorrhizae, water extraction concentrates, and precipitate with ethanol reclaims the pure Radix Salviae Miltiorrhizae extract that gets.
Radix Notoginseng extract: get Radix Notoginseng, extracting in water concentrates, and crosses macroporous adsorbent resin, use pure eluting, eluent concentrated Radix Notoginseng extract.
Drop pill mean with solid or liquid medicine with splash into a kind of preparation that contraction forms in the immiscible condensing agent after substrate is mixed.It has following characteristics: 1. specific surface area is big, and rate of release is fast in the body, the bioavailability height; 2. because drops itself is the solid dispersion that medicine and substrate are made by heating and melting, drug molecule is dispersed directly in the substrate, so drug molecule can absorb directly into blood through sublingual vein, avoided having guaranteed the abundant absorption of effective ingredient because of the long-living first pass effect of gastrointestinal absorption; 3. the drops volume is little, is convenient for carrying, and taking dose is easy to grasp.
Below by effect experiment beneficial effect of the present invention is described.
Pharmacodynamics test
A kind of folium ginkgo dripping pill of the present invention and Ginaton tablets 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 180 ± 10g, the quality certification number: SCXK11-00-0008 is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..
1.2 medicine and reagent: folium ginkgo dripping pill, adopt embodiment 14 method manufacturings, sky, Tianjin Shi Li group provides lot number: 001204; Positive control drug, Ginaton tablets (active component is a Folium Ginkgo extract), Dr Willmar Schwabe produces, lot number: 2770601, import drugs registration certificate number: X20000521.
1.3 instrument: XTT stero microscope, Yunnan Optical Instruments Factory's product; The AEG-220 electronic analytical balance, Japanese Shimadzu company product; The desk-top dentistry car of 307-6, Shanghai Dental Medical Apparatus and Instrument Factory's product.
2. experimental technique
2.1 grouping and administration: laboratory animal is divided into 6 groups at random, it is Sham-operated control group, model I group, model II group, folium ginkgo dripping pill treatment group, Ginaton tablets equivalent group (wherein EGB 24mg/kg), Ginaton tablets high dose group (wherein EGB 48mg/kg) animal gastric infusion two days continuously earlier, administration in the 3rd day was performed a surgical operation after 90 minutes, and postoperative continued gastric infusion one day.Wherein sham operated rats and model I group gavages the 0.5%cmc of equivalent, and model II group gavages Polyethylene Glycol (the PEG)-0.5%cmc solution (wherein PEG 25mg/kg) 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 (350mg/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 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 minute.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%TTC 1.5ml, 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.Learn paired comparison t check, table 4 as a result between check employing group by statistics.
Table 1 folium ginkgo dripping pill is to the influence of rat nervous symptoms and cerebral infarction scope
Annotate: compare with corresponding model,
*P＜0.05,
*P＜0.01; Compare with sham operated rats,
△ △P＜0.01 is compared with Ginaton, P＜0.01.
| Group | Number of animals | Dosage | Cerebral infarction scope (%) | Nervous symptoms scoring 24h | |
| It is heavy to account for full brain | It is heavy to account for the Ipsilateral brain | ||||
| Sham operated rats | 12 | 0±0 ** | 0±0 ** | 0±0 ** | |
| Model I group | 12 | 2.66±1.10 △△ | 5.10±2.11 △△ | 2.92±0.79 △△ | |
| Model II group | 12 | 2.95±1.15 △△ | 5.63±2.18 △△ | 3.17±0.72 △△ | |
| Ginaton (etc.) | 12 | 24 | 2.58±0.74 | 4.92±1.42 | 2.42±0.51 |
| Ginaton (height) | 11 | 48 | 2.07±3.05 | 3.96±3.05 | 2.55±0.52 |
| Folium ginkgo dripping pill | 12 | 25 | 1.58±0.45 ** | 3.03±0.84 ** | 2.25±0.62 * |
Conclusion: as can be seen from the above table, folium ginkgo dripping pill of the present invention is better than Ginaton tablets at aspects such as improving rat nervous symptoms and cerebral infarction scope, has significant difference (P＜0.01).
The specific embodiment
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;
(2) above-mentioned Folium Ginkgo extract 100g is mixed with 300 polyethylene glycol 6000s;
(3) preparation of product: get above-mentioned Folium Ginkgo extract and polyethylene glycol 6000 and be heated to 85 ℃, behind the change material 20min, the drip irrigation that moves into the drop pill machine remains on 85 ℃.In the liquid paraffin of medicine liquid droplet to 7～8 ℃, take out drop pill, remove liquid paraffin, select ball, promptly.
Embodiment 2
(1) preparation of Folium Ginkgo extract: get the 1000g 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;
(2) preparation of Radix Astragali extract: get radix astragali coarse powder 200g, use water extraction 2 times, amount of water is 10 times of the Radixs Astragali for the first time, 2 hours, add 8 times of water gagings, 1.5 hours for the second time, merge extractive liquid, filters, and being concentrated into medicine liquid volume is 1: 1 with medical material amount ratio, the ethanol of adding 90%, be medicinal liquid contain determining alcohol to 70-75%, left standstill 12 hours, take out supernatant, concentrating under reduced pressure reclaims ethanol, gets the Milkvetch Root extract;
(3) getting above-mentioned Folium Ginkgo extract 100g mixes with 8g Radix Astragali extract and 300g Macrogol 4000;
(4) preparation of product: get above-mentioned Folium Ginkgo extract, Radix Astragali extract and Macrogol 4000 and be heated to 86 ℃, behind the change material 25min, the drip irrigation that moves into the drop pill machine remains on 89 ℃.In the liquid paraffin of medicine liquid droplet to 7～8 ℃, take out drop pill, remove liquid paraffin, select ball, promptly.
Embodiment 3
(1) preparation of Folium Ginkgo extract: get the 1000g Folium Ginkgo, add the water of 5 times of amounts, decoct each 2 hours 2 times, temperature is 50～60 ℃, and merge extractive liquid, concentrates, and it is refining to cross macroporous adsorbent resin (AB-8), use 80% ethanol elution, eluent concentrates and reclaims ethanol, gets Folium Ginkgo extract;
(2) getting above-mentioned Folium Ginkgo extract 100g mixes with 300g Macrogol 4000,6000 mixture (ratio is 1: 0.01);
(3) preparation of product: get above-mentioned Folium Ginkgo extract and Macrogol 4000,6000 mixture (ratio is 1: 0.01) are heated to 88 ℃, change material 30min after, the drip irrigation that moves into the drop pill machine remains on 86 ℃.In the liquid paraffin of medicine liquid droplet to 7～8 ℃, take out drop pill, remove liquid paraffin, select ball, promptly.
Embodiment 4
(1) preparation of Folium Ginkgo extract: get the 1000g Folium Ginkgo, add 5 times of amount 65% ethanol, heating and refluxing extraction 2 times, each 1 hour, 60 ℃ of temperature, merge extractive liquid,, concentrate, it is refining to cross macroporous adsorbent resin (D101), uses 85% ethanol elution, eluent concentrates and reclaims ethanol, gets Folium Ginkgo extract;
(2) preparation of Radix Ginseng extract: get Radix Ginseng section 100g, 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;
(3) get above-mentioned Folium Ginkgo extract 100g, Radix Ginseng extract 4g and 300g Macrogol 4000,6000 mixture (ratio is 1: 20) mix;
(4) preparation of product: get above-mentioned Folium Ginkgo extract, Radix Ginseng extract and Macrogol 4000,6000 mixture (ratio is 1: 20) are heated to 90 ℃, change material 40min after, the drip irrigation that moves into the drop pill machine remains on 88 ℃.In the liquid paraffin of medicine liquid droplet to 7～8 ℃, take out drop pill, remove liquid paraffin, select ball, promptly.
Embodiment 5
(1) preparation of Folium Ginkgo extract: get and pulverize Folium Ginkgo 1000g, adopt CO
2Supercritical extraction gets Folium Ginkgo extract, and process conditions are that temperature is 45 ℃, and extracting pressure is 25Mpa, flow 0.8ml/min, 2 hours time.Ginkgo total flavones 〉=24% wherein, terpene lactones 〉=6%;
(2) getting above-mentioned Folium Ginkgo extract 100g mixes with 300g Macrogol 4000,6000 mixture (ratio is 1: 40);
(3) preparation of product: get said mixture and be heated to 90 ℃, behind the change material 35min, the drip irrigation that moves into the drop pill machine remains on 88 ℃.In the liquid paraffin of medicine liquid droplet to 7～8 ℃, take out drop pill, remove liquid paraffin, select ball, promptly.
Contrast experiment's example
Folium ginkgo dripping pill of the present invention and Gin Kgo Plus, SHUXUENING PIAN, GinkgoBiloba sheet and capsule etc. compare, and investigate its external disintegration.The result shows that the molten diffusing speed of folium ginkgo dripping pill is fast, and disintegrate is obviously faster than tablet, and is approaching with the Gingomax capsule, but obviously faster than Sundown Herbals Gingkocapsule.
(1) reagent: folium ginkgo dripping pill, sky, Tianjin Shi Li group modern Chinese medicine institute provides, and presses embodiment 5 method productions, lot number: 20010222; Gin Kgo Plus, Kang Enbei pharmaceutical Co. Ltd in Zhejiang produces, lot number: 000713; SHUXUENING PIAN, Yangtze River Pharma Inc. produces, lot number: 000,420 3; Kingo Vital Tablet OY VALIORAVINTOAB produces, lot number: 01 2001 BA00; The GinkgoBiloba capsule, Ginkgomax company produces, lot number: 00182; The GinkgoBiloba capsule, Sundown Herbals company produces.
(2) method and result: according to " method of Chinese pharmacopoeia (2000 editions) appendix disintegration is measured, and it is the hanging basket of φ 0.425mm that drop pill is selected mesh size for use, and it is the hanging basket of φ 2mm that other tablet, capsule are selected mesh size for use.The results are shown in Table 2.
The different preparations of table 2 Semen Ginkgo in water disintegration experimental result
Mesh size
Name of product dosage form manufacturer lot number disintegration time (min)
(mm)
Sky, gingko drop pill drop pill Tianjin scholar's power 20,010,222 0.425 4.89 ± 0.65
Sky, gingko drop pill drop pill Tianjin scholar's power 20,010,222 2.0 3.88 ± 0.37
Taponin tablet Zhejiang Kang Enbei 000,713 2.0 10.81 ± 1.04
SHUXUENING PIAN tablet Yangtze River Pharmaceutical 0,004,203 2.0 28.28 ± 3.31
Kingo OY VALIORAVINTO
Tablet 01 2001 BA00 2.0 19.69±0.47
Vital AB
Ginkgo Capsule Ginkgomax 00182 2.0 3.64±0.13
Biloba
Ginkgo Capsule Sundown Herbals 2.0 13.75±1.25
Biloba
Embodiment 6
(1) preparation of Folium Ginkgo extract: getting ginkgo biloba crude extract is raw material, adopt high-speed countercurrent chromatography (HSCCC) preparation Folium Ginkgo extract, adopt the solvent system of chloroform methanol water (4: 3: 2), after treating that two-phase solvent fully mixes, face with preceding it is separated, at room temperature, make down mobile phase mutually, on the phase that fixes mutually, flow velocity with 2.0ml/min, by head end eluting caudad, main frame just changes, and rotating speed is 800r/min, the immobile phase retention is 78%, sample introduction 2.0ml regularly collects fraction, promptly;
(2) preparation of Rhizoma Atractylodis Macrocephalae extract: get Rhizoma Atractylodis Macrocephalae medical material 100g, extracting in water 2 times adds the water of 7 times of amounts the first time, time is 3 hours, is 5 times of water gagings for the second time, and the time is 1.5 hours, merge extractive liquid,, being concentrated into medicine liquid volume is 1: 1 with the crude drug ratio, promptly gets Rhizoma Atractylodis Macrocephalae extract;
(3) get above-mentioned Folium Ginkgo extract 100g, Rhizoma Atractylodis Macrocephalae extract 5g and sweeting agent 0.5g and 300g Macrogol 4000,6000 mixture (ratio is 1: 80) mix;
(4) preparation of product: get above-mentioned Folium Ginkgo extract, Rhizoma Atractylodis Macrocephalae extract and Macrogol 4000,6000 mixture (ratio is 1: 80) are heated to 88 ℃, change material 100min after, the drip irrigation that moves into the drop pill machine remains on 85 ℃.In the liquid paraffin of medicine liquid droplet to 7～8 ℃, take out drop pill, remove liquid paraffin, select ball, promptly.
Embodiment 7
(1) preparation of Folium Ginkgo extract: adopt enzyme process to make Folium Ginkgo extract;
(2) get above-mentioned Folium Ginkgo extract 100g, 300g Macrogol 4000,6000 mixture (ratio is 1: 99.9) mix;
(3) preparation of product: get above-mentioned Folium Ginkgo extract and Polyethylene Glycol Macrogol 4000,6000 mixture (ratio is 1: 99.9) are heated to 90 ℃, change material 40min after, the drip irrigation that moves into the drop pill machine remains on 88 ℃.In the liquid paraffin of medicine liquid droplet to 7～8 ℃, take out drop pill, remove liquid paraffin, select ball, promptly.
Embodiment 8
(1) getting the 100g Folium Ginkgo extract mixes with the 400g polyethylene glycol 6000;
(2) Folium Ginkgo extract preparation method, and Manufacturing Method of Products is with embodiment 1.
Embodiment 9
(1) preparation of Fructus Schisandrae Chinensis extrat: get the 100g schisandra chinensis medicinal material, add the ethanol of 4 times of amounts 85%, reflux, extract, 3 times, each 2 hours, merge extractive liquid, filtered, and concentrating under reduced pressure reclaims ethanol and gets Fructus Schisandrae Chinensis extrat;
(2) get Folium Ginkgo extract 100g, 5g Radix Astragali extract, 3g Fructus Schisandrae Chinensis extrat and 400g polyethylene glycol 6000 mix;
(3) preparation of Radix Astragali extract is with embodiment 2;
(4) preparation of the preparation of Folium Ginkgo extract and product is with embodiment 2.
Embodiment 10
(1) preparation of Poria extract: get Poria 100g, section adds 5 times of water gagings, heating extraction 3 times, the time was respectively 3 hours for the first time, 2 hours for the second time, 1 hour for the third time, merge extractive liquid, filters, and is evaporated to every 1ml medicinal liquid and is equivalent to the 7g raw medicinal herbs, adding 90% ethanol makes it contain the alcohol amount to reach 75%, centrifugal, collect supernatant, concentrate and remove ethanol and get Poria extract;
(2) get Folium Ginkgo extract 100g, Poria extract 8g and 400g Macrogol 4000,6000 mixture (ratio is 1: 0.01) mix;
(3) preparation method of the preparation method of Semen Ginkgo extrac and product is with embodiment 3.
Embodiment 11
(1) get Folium Ginkgo extract 100g (total flavones 〉=24%, terpene lactones 〉=6%), 400g Macrogol 4000,6000 mixture (ratio is 1: 20) mix;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 4.
Embodiment 12
(1) preparation of Radix Paeoniae Alba extract: get the 100g Radix Paeoniae Alba, pulverize, add 6 times of water gagings and extract 2 times, each 2 hours, merge extractive liquid, was evaporated to every 1ml medicinal liquid and is equivalent to the 5g raw medicinal herbs, add 95% ethanol and make it contain alcohol amount to reach 80%, get supernatant, concentrate and reclaim ethanol and get Radix Paeoniae Alba extract;
(2) get Folium Ginkgo extract 100g, Radix Paeoniae Alba extract 7g and sweeting agent 0.1g and 400g Macrogol 4000,6000 mixture (ratio is 1: 40) mix;
(3) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 5.
Embodiment 13
(1) gets Folium Ginkgo extract 100g and 400g Macrogol 4000,6000 mixture (ratio is 1: 80) mixing;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 6.
Contrast experiment's example
The body giving drugs into nose is for dynamic experiment
Bilobalide pharmacokinetic in the folium ginkgo dripping pill
This test utilizes bilobalide (A, B and bilobalide)
3H label Radioactive tracer techniques have been studied the oral feature of its bilobalide pharmacokinetics afterwards of two kinds of preparation rabbit of a kind of folium ginkgo dripping pill of the present invention and Ginkgomax capsule (Finland's product).The result shows, the identical dosage group pharmacokinetic parameter AUC of different lactones is close with Cmax numerical value in folium ginkgo dripping pill of the present invention and the capsule, and Tpeak and t1/2ka drop pill are starkly lower than capsule.The absworption peak of bilobalide comes soon than capsule in the folium ginkgo dripping pill of the present invention, and peak time generally shifts to an earlier date 30-45min in the blood, shows that folium ginkgo dripping pill of the present invention has the characteristics of fast Absorption than capsule formulation.
1. experiment material
1.1 medicine: ginkalide A, B and bilobalide standard substance HPLC are pure, lot number 0864-9902, and Nat'l Pharmaceutical ﹠ Biological Products Control Institute provides.The Ginkgomax capsule that control drug adopts Finland Hankintatukku company to produce, every capsules content 270mg contains EGb 61mg, wherein contains GIN 15mg, lot number: 08022003; Folium ginkgo dripping pill adopts the method manufacturing of embodiment 13, provides lot number by sky, Tianjin Shi Li group modern Chinese medicine institute: 010507.
1.2 reagent:
3H-ginkalide A intrinsic specific activity 74.83MBq/mg,
3H-ginkalide B intrinsic specific activity 109.83MBq/mg,
3H-bilobalide intrinsic specific activity 90.40MBq/mg., three kinds
3The H label does not all contain
3H impurity is provided by China Atomic Energy Science Research Institute's Isotope Research.Scintillator: 2.5-diphenyl azoles (2.5-Diphenyloxazol) the abbreviation PPO that makes mute, 2.2-is provided by Fluka company Brace two (5-phenyl make azoles)-P-Phenyl-bis (5-Phenyloxazole) 1 POPOP that abridges.Scintillation solution: 0.3%PPO and 0.03%POPOP and equal-volume dimethylbenzene and ethylene glycol monomethyl ether miscible fluid.
1.3 animal: healthy white big ear rabbit body weight 1.5 ± 0.1Kg, male and female half and half are provided by Jin Nan experimental animal feeding center, Tianjin, the quality certification number: 2001016.
2. experimental technique
2.1 get 1.0mci's
3H-ginkalide A, B and
3Grind well dry back in H-bilobalide (50% alcoholic solution) the adding 8.0gGinkgomax content and move into grinding 20min in the KL-50 ball mill.Taking by weighing 120 ± 5mg (containing Folium Ginkgo extract 30mg approximately) powder packs into standby in No. 4 capsules that Shanghai capsule factory produces.
2.2 experiment grouping and sample collection: experiment divides drop pill and two kinds of dosage forms of capsule, every kind of dosage form is established ginkalide A, B and three kinds of medicine groups of bilobalide, every kind of medicine group is established three dosage groups (Folium Ginkgo extract 20,40 and 60mg/Kg), 6 animals of every experimental group.Experiment adopts homemade balling iron that drop pill or capsule are dropped in the animal subject stomach, dispensing back 10,20,40,60,90,120,150,180,240,300,360 and 480min get the about 0.8ml of blood from the animal auricular vein, the citric acid anticoagulant, it is standby that the centrifugal 15-20min of 5000rpm gets blood plasma.
2.3 sample treatment and result calculate: 0.4ml test serum slurry adds the 0.4ml Digestive system, and (cross nitronic acid: hydrogen peroxide=2: 1) being mixed is placed on that digestion 2h is limpid solution in 60 ℃ of water-baths, get Digestive system 0.4ml and be added in the measuring cup that contains the 10ml scintillation solution and make homogeneous phase solution, put LKB-1217 liquid scintillation counting instrumentation amount radioactivity.The radioactivity of sample takes advantage of extension rate to be converted into the radioactivity of every milliliter of blood plasma, promptly tries to achieve the micrograms of every milliliter of blood plasma of sample again divided by the specific activity of label.
3. conclusion
Bilobalide pharmacokinetic parameter: according to ginkalide A, B and bilobalide content in blood plasma in folium ginkgo dripping pill and the capsule different dosing dosage, (be that 3P97) Be closes and handles the pharmacokinetic parameter try to achieve separately, AUC, Cmax, Tpeak and the t1/2ka of ginkalide A, B and bilobalide oral absorption process is isoparametric relatively to see the following form 3,4,5 to utilize pharmacokinetics software.
The comparison of the pharmacokinetic parameter of ginkalide A in table 3 folium ginkgo dripping pill and the Ginkgomax capsule
| Pharmacokinetic parameter | 20mg | 40mg | 60mg | |||
| Drop pill | Capsule | Drop pill | Capsule | Drop pill | Capsule | |
| T1/2(a) | 12.0133 | 68.4431 | 15.4465 | 82.4571 | 9.8422 | 77.9553 |
| T(peak) | 66.3086 | 167.7544 | 78.7773 | 182.7186 | 55.6459 | 178.6019 |
| C(max) | 0.8950 | 0.9067 | 1.3740 | 1.3937 | 1.9530 | 1.9109 |
| AUC | 711.565 | 489.529 | 1050.132 | 770.247 | 1396.159 | 1051.828 |
The comparison of the pharmacokinetic parameter of ginkalide B in table 4 folium ginkgo dripping pill and the Ginkgomax capsule
| Pharmacokinetic parameter | 20mg | 40mg | 60mg | |||
| Drop pill | Capsule | Drop pill | Capsule | Drop pill | Capsule | |
| T1/2(a) | 14.5363 | 42.3246 | 13.7385 | 51.3624 | 9.0794 | 57.5323 |
| T(peak) | 70.4678 | 81.3862 | 63.2668 | 162.5729 | 49.2334 | 157.112 |
| C(max) | 0.6655 | 0.6492 | 1.1127 | 0.9392 | 1.5591 | 1.4112 |
| AUC | 401.842 | 396.2154 | 536.714 | 624.278 | 875.866 | 779.758 |
The comparison of the pharmacokinetic parameter of bilobalide in table 5 folium ginkgo dripping pill and the Ginkgomax capsule
| Pharmacokinetic parameter | 20mg | 40mg | 60mg | |||
| Drop pill | Capsule | Drop pill | Capsule | Drop pill | Capsule | |
| T1/2(a) | 13.41 | 55.4142 | 15.2795 | 70.0042 | 12.9959 | 63.6280 |
| T(peak) | 64.91 | 184.814 | 66.5191 | 162.342 | 62.9845 | 153.934 |
| C(max) | 0.749 | 0.7332 | 1.2015 | 1.0493 | 1.6567 | 1.5162 |
| AUC | 415.0 | 591.546 | 541.437 | 521.821 | 889.372 | 744.491 |
Last table prompting: folium ginkgo dripping pill and capsule formulation AUC are close with Cmax numerical value, and Tpeak and t1/2ka drop pill are starkly lower than capsule.The absworption peak that shows bilobalide in the folium ginkgo dripping pill of the present invention comes soon than capsule, and peak time generally shifts to an earlier date 30-45min in the blood, shows that folium ginkgo dripping pill of the present invention has the characteristics of fast Absorption than capsule formulation.
Embodiment 14
(1) (ratio is to mix at 1: 99.91 to get Folium Ginkgo extract 100g and 400g Macrogol 4000,6000 mixture;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 7.
Embodiment 15
(1) gets Folium Ginkgo extract 100g, mix with the 200g polyethylene glycol 6000;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 1.
Embodiment 16
(1) preparation of Radix Salviae Miltiorrhizae extract: get the 100g Radix Salviae Miltiorrhizae, pulverize, add the water of 5 times of amounts, decocted 2 hours, and filtered, extract for the second time, add 4 times of water gagings, the time is 1 hour, merging filtrate, being concentrated into medicine liquid volume is 1: 1 with crude drug amount ratio, adds 95% ethanol, makes medicinal liquid contain the alcohol amount and reaches 70%, leave standstill, get supernatant, concentrate and reclaim ethanol, get Radix Salviae Miltiorrhizae extract;
(2) get Folium Ginkgo extract 100g, Radix Salviae Miltiorrhizae extract 8g and 200g Macrogol 4000 mix;
(3) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 2.
Embodiment 17
(1) get Folium Ginkgo extract 100g, Ginkgo total flavones 〉=24% wherein, terpene lactones 〉=6% mixes with 200g Macrogol 4000,6000 mixture (ratio is 1: 0.01);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 3.
Embodiment 18
(1) preparation of Radix Notoginseng extract: get Radix Notoginseng 100g, add 7 times of water gagings, heating extraction 2 times, each 2 hours, merge extractive liquid,, last macroporous adsorbent resin (AB-8) is used 80% ethanol elution, collects eluent, and concentrating under reduced pressure gets Radix Notoginseng extract;
(2) get Folium Ginkgo extract 100g, Radix Notoginseng extract 7g and 200g Macrogol 4000,6000 mixture (ratio is 1: 20) mix;
(3) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 4.
Embodiment 19
(1) preparation of Radix Notoginseng extract: with embodiment 18.
(2) get Folium Ginkgo extract 100g, Radix Notoginseng extract 7g, and 200g Macrogol 4000,6000 mixture (ratio is 1: 20) mix;
(3) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 4.
Embodiment 20
(1) getting Folium Ginkgo extract 100g mixes with 200g Macrogol 4000,6000 mixture (ratio is 1: 40);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 5.
Embodiment 21
(1) gets Folium Ginkgo extract 100g, mix with 200g Macrogol 4000,6000 mixture (ratio is 1: 80);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 6.
Embodiment 22
(1) getting Folium Ginkgo extract 100g mixes with 200g Macrogol 4000,6000 mixture (ratio is 1: 99.9);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 7.
Embodiment 23
(1) get Folium Ginkgo extract 100g Ginkgo total flavones 〉=24%, terpene lactones 〉=6%, the 150g polyethylene glycol 6000 mixes;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 1.
Embodiment 24
(4) get Folium Ginkgo extract 100g, mix with the 150g Macrogol 4000;
(5) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 2.
Embodiment 25
(1) preparation of Radix Ginseng extract: with embodiment 4;
(2) preparation of Radix Paeoniae Alba extract: with embodiment 12;
(3) get Folium Ginkgo extract 100g, Radix Ginseng extract 4g, Radix Paeoniae Alba extract 4g and 150g Macrogol 4000,6000 mixture (ratio is 1: 0.01) mix;
(4) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 3.
Embodiment 26
(1) getting Folium Ginkgo extract 100g mixes with 150g Macrogol 4000,6000 mixture (ratio is 1: 20);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 4.
Embodiment 27
(1) get Folium Ginkgo extract 100g, Ginkgo total flavones 〉=24% wherein, terpene lactones 〉=6% mixes with 150g Macrogol 4000,6000 mixture (ratio is 1: 40);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 5.
Embodiment 28
(1) preparation of Poria extract: with embodiment 10;
(2) preparation of Fructus Schisandrae Chinensis extrat: with embodiment 9;
(3) preparation of Radix Notoginseng extract: with embodiment 18;
(4) getting Folium Ginkgo extract 100g mixes with 3g Poria extract, 3g Fructus Schisandrae Chinensis extrat 3g Radix Notoginseng extract and 150g Macrogol 4000,6000 mixture (ratio is 1: 80);
(5) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 6.
Embodiment 29
(1) getting Folium Ginkgo extract 100g mixes with 150g Macrogol 4000,6000 mixture (ratio is 1: 99.9);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 7.
Embodiment 30
(1) getting Folium Ginkgo extract 100g mixes with the 600g polyethylene glycol 6000;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 1.
Embodiment 31
(1) preparation of Radix Salviae Miltiorrhizae extract: with embodiment 16;
(2) preparation of Radix Notoginseng extract: with embodiment 18;
(3) get Folium Ginkgo extract 100g, mix with 5g Radix Salviae Miltiorrhizae extract, 2g Radix Notoginseng extract and 600g Macrogol 4000;
(4) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 2.
Embodiment 32
(1) getting Folium Ginkgo extract 100g mixes with 600g Macrogol 4000,6000 mixture (ratio is 1: 0.01);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 3.
Embodiment 33
(1) getting Folium Ginkgo extract 100g (total flavones 〉=24%, terpene lactones 〉=6%) mixes with 600g Macrogol 4000,6000 mixture (ratio is 1: 20);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 4.
Embodiment 34
(1) preparation of Radix Salviae Miltiorrhizae extract: with embodiment 16;
(2) preparation of Radix Notoginseng extract: with embodiment 18;
(3) preparation of Radix Ginseng extract: with embodiment 14;
(4) get Folium Ginkgo extract 100g, mix with 2g Radix Salviae Miltiorrhizae extract, 2g Radix Ginseng extract, 2g Radix Notoginseng extract, 2g sweeting agent and 600g Macrogol 4000,6000 mixture (ratio is 1: 40);
(5) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 5.
Embodiment 35
(1) getting Folium Ginkgo extract 100g mixes with 600g Macrogol 4000,6000 mixture (ratio is 1: 80);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 6.
Embodiment 36
(1) getting Folium Ginkgo extract 100g mixes with 600g Macrogol 4000,6000 mixture (ratio is 1: 99.9);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 7.
Embodiment 37
(1) getting Semen Ginkgo extrac 100g mixes with the 800g polyethylene glycol 6000;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 1.
Embodiment 38
(1) getting Semen Ginkgo extrac 100g mixes with the 800g Macrogol 4000;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 2.
Embodiment 39
(1) preparation of Radix Notoginseng extract: with embodiment 18;
(2) getting Semen Ginkgo extrac 100g mixes with 800g Macrogol 4000,6000 mixture (ratio is 1: 0.01);
(3) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 3.
Embodiment 40
(1) getting Semen Ginkgo extrac 100g mixes with 800g Macrogol 4000,6000 mixture (ratio is 1: 20);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 4.
Embodiment 41
(1) getting Semen Ginkgo extrac 100g mixes with 800g Macrogol 4000,6000 mixture (ratio is 1: 40);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 5.
Embodiment 42
(1) getting Semen Ginkgo extrac 100g mixes with 800g Macrogol 4000,6000 mixture (ratio is 1: 80);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 6.
Embodiment 43
(1) getting Semen Ginkgo extrac 100g mixes with 800g Macrogol 4000,6000 mixture (ratio is 1: 99.9);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 7.
Embodiment 44
(1) getting Semen Ginkgo extrac 100g mixes with 1000g polyethylene glycol 6000 mixture;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 1.
Embodiment 45
(1) getting Semen Ginkgo extrac 100g mixes with 1000g Macrogol 4000 mixture;
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 2.
Embodiment 46
(1) getting Semen Ginkgo extrac 100g mixes with 1000g Macrogol 4000,6000 mixture (ratio is 1: 20);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 3.
Embodiment 47
(1) getting Semen Ginkgo extrac 100g mixes with 1000g Macrogol 4000,6000 mixture (ratio is 1: 40);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 4.
Embodiment 48
(1) getting Semen Ginkgo extrac 100g mixes with 1000g Macrogol 4000,6000 mixture (ratio is 1: 60);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 5.
Embodiment 49
(1) getting Semen Ginkgo extrac 100g mixes with 1000g Macrogol 4000,6000 mixture (ratio is 1: 80);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 6.
Embodiment 50
(1) getting Semen Ginkgo extrac 100g mixes with 1000g Macrogol 4000,6000 mixture (ratio is 1: 99.9);
(2) manufacture method of the preparation method of Folium Ginkgo extract and product is with embodiment 7.
Claims (10)
1. folium ginkgo dripping pill, comprise Folium Ginkgo extract and Polyethylene Glycol, it is characterized in that Folium Ginkgo extract and Macrogol 4000, perhaps with polyethylene glycol 6000, perhaps the weight ratio with Macrogol 4000 and polyethylene glycol 6000 mixture is 1: 1.5～10.
2. folium ginkgo dripping pill, comprise through water or organic solvent extraction and obtain Folium Ginkgo extract, or behind water or organic solvent extraction the refining and Folium Ginkgo extract that obtains of reuse adsorbent resin, or the Folium Ginkgo extract that obtains with supercritical extraction, or the Folium Ginkgo extract that obtains with the high-speed countercurrent chromatography extraction, or adding the Folium Ginkgo extract that obtains with enzyme process, the weight ratio that it is characterized in that the mixture of described Folium Ginkgo extract and Macrogol 4000 or polyethylene glycol 6000 or Macrogol 4000 and polyethylene glycol 6000 is 1: 1.5～10.
3. folium ginkgo dripping pill, the total flavones of Folium Ginkgo extract 〉=24% wherein, terpene lactones 〉=6%, the weight ratio that it is characterized in that the mixture of described Folium Ginkgo extract and Macrogol 4000 or polyethylene glycol 6000 or Macrogol 4000 and polyethylene glycol 6000 is 1: 1.5～10.
4. according to claim 1,2 or 3 described folium ginkgo dripping pills, it is characterized in that Folium Ginkgo extract and Macrogol 4000, perhaps with polyethylene glycol 6000, perhaps the weight ratio with Macrogol 4000 and polyethylene glycol 6000 mixture is 1: 2～4.
5. according to claim 1,2 or 3 described folium ginkgo dripping pills, the weight ratio that it is characterized in that the mixture of described Macrogol 4000 and polyethylene glycol 6000 is 1: 0.01～99.9.
6. according to claim 1,2 or 3 described folium ginkgo dripping pills, it is characterized in that in component, having described Folium Ginkgo extract and the Polyethylene Glycol, also contain other auxiliary composition and effectiveness or inactive component, its content is below 10% of Folium Ginkgo extract weight.
7. folium ginkgo dripping pill according to claim 6, it is characterized in that described other adjuvant component is the conventional extract of following Chinese medicine: the Radix Astragali, Radix Ginseng, the Rhizoma Atractylodis Macrocephalae, Poria, Fructus Schisandrae Chinensis, the Radix Paeoniae Alba, Radix Salviae Miltiorrhizae, Radix Notoginseng, no matter be single using or the combination in any between them, its total amount is below 10% of Folium Ginkgo extract weight.
8. folium ginkgo dripping pill according to claim 6 is characterized in that Folium Ginkgo extract and Macrogol 4000, and perhaps with polyethylene glycol 6000, perhaps the weight ratio with Macrogol 4000 and polyethylene glycol 6000 mixture is 1: 2～4.
9. folium ginkgo dripping pill according to claim 6, the weight ratio that it is characterized in that the mixture of described Macrogol 4000 and polyethylene glycol 6000 is 1: 0.01～99.9.
10. a Chinese medicine dripping pills preparation is made up of Folium Ginkgo extract and Polyethylene Glycol, and the two weight proportion is 1: 2-4, described Folium Ginkgo extract makes with solvent extraction, Ginkgo total flavones content 〉=24% wherein, Folium Ginkgo terpene lactones content 〉=6%.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN02131267.2A CN1210048C (en) | 2002-09-23 | 2002-09-23 | Gingko leaf drop pill |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN02131267.2A CN1210048C (en) | 2002-09-23 | 2002-09-23 | Gingko leaf drop pill |
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| CN1485061A CN1485061A (en) | 2004-03-31 |
| CN1210048C true CN1210048C (en) | 2005-07-13 |
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| CN02131267.2A Expired - Lifetime CN1210048C (en) | 2002-09-23 | 2002-09-23 | Gingko leaf drop pill |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101439077B (en) * | 2007-11-23 | 2012-06-27 | 河北以岭医药研究院有限公司 | Medicament containing dalbergia heartwood for treating blood vessel endothelium dysfunction and preparation method thereof |
| CN101780030A (en) * | 2010-03-09 | 2010-07-21 | 贵州大学 | Ginkgo flavone aglycone solid dispersion and preparation method thereof |
| CN106880661A (en) * | 2017-03-14 | 2017-06-23 | 哈尔滨紫苏生命科技健康产业有限公司 | Pseudo-ginseng ginkgo leaf purple perilla method for producing soft capsule |
| CN110946898A (en) * | 2019-12-19 | 2020-04-03 | 西藏越星泰达医药科技有限责任公司 | Dripping pill preparation |
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