CN101194910A - Dropping pills containing acegastrodine and method for preparing the same - Google Patents
Dropping pills containing acegastrodine and method for preparing the same Download PDFInfo
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- CN101194910A CN101194910A CNA2006101299711A CN200610129971A CN101194910A CN 101194910 A CN101194910 A CN 101194910A CN A2006101299711 A CNA2006101299711 A CN A2006101299711A CN 200610129971 A CN200610129971 A CN 200610129971A CN 101194910 A CN101194910 A CN 101194910A
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- Prior art keywords
- acegastrodine
- drop pill
- adjuvant
- xylitol
- starch
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- 239000006187 pill Substances 0.000 title claims abstract description 142
- HGUDVDQXCUHOED-YMQHIKHWSA-N [(2r,3r,4s,5r,6s)-3,4,5-triacetyloxy-6-[4-(hydroxymethyl)phenoxy]oxan-2-yl]methyl acetate Chemical compound CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1OC1=CC=C(CO)C=C1 HGUDVDQXCUHOED-YMQHIKHWSA-N 0.000 title claims description 107
- 238000000034 method Methods 0.000 title abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 54
- 238000002360 preparation method Methods 0.000 claims abstract description 34
- -1 acetyl gastrodine Chemical compound 0.000 claims abstract description 5
- 239000002671 adjuvant Substances 0.000 claims description 71
- 239000000203 mixture Substances 0.000 claims description 60
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 46
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 46
- 239000000811 xylitol Substances 0.000 claims description 46
- 235000010447 xylitol Nutrition 0.000 claims description 46
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 46
- 229960002675 xylitol Drugs 0.000 claims description 46
- 238000002156 mixing Methods 0.000 claims description 37
- 229920002472 Starch Polymers 0.000 claims description 34
- 239000008107 starch Substances 0.000 claims description 34
- 235000019698 starch Nutrition 0.000 claims description 34
- 239000000758 substrate Substances 0.000 claims description 30
- 238000009413 insulation Methods 0.000 claims description 26
- 238000010438 heat treatment Methods 0.000 claims description 25
- 239000007788 liquid Substances 0.000 claims description 25
- 238000002844 melting Methods 0.000 claims description 25
- 230000008018 melting Effects 0.000 claims description 25
- 238000003756 stirring Methods 0.000 claims description 25
- 239000002826 coolant Substances 0.000 claims description 24
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 23
- 239000008101 lactose Substances 0.000 claims description 23
- 229920002545 silicone oil Polymers 0.000 claims description 21
- 235000010489 acacia gum Nutrition 0.000 claims description 17
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 17
- 229940057995 liquid paraffin Drugs 0.000 claims description 9
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000000945 filler Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 5
- 239000008158 vegetable oil Substances 0.000 claims description 5
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 4
- 229920001817 Agar Polymers 0.000 claims description 4
- 229920000858 Cyclodextrin Polymers 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- 239000008272 agar Substances 0.000 claims description 4
- 239000000783 alginic acid Substances 0.000 claims description 4
- 235000010443 alginic acid Nutrition 0.000 claims description 4
- 229920000615 alginic acid Polymers 0.000 claims description 4
- 229960001126 alginic acid Drugs 0.000 claims description 4
- 150000004781 alginic acids Chemical class 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 229940032147 starch Drugs 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 6
- 235000019640 taste Nutrition 0.000 abstract description 5
- 206010019233 Headaches Diseases 0.000 abstract description 3
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 3
- 235000013373 food additive Nutrition 0.000 abstract description 3
- 239000002778 food additive Substances 0.000 abstract description 3
- 231100000869 headache Toxicity 0.000 abstract description 3
- 230000007958 sleep Effects 0.000 abstract description 3
- 206010039897 Sedation Diseases 0.000 abstract 1
- 230000001272 neurogenic effect Effects 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 230000036280 sedation Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 16
- 238000009472 formulation Methods 0.000 description 13
- 238000012360 testing method Methods 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 10
- 241000196324 Embryophyta Species 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 210000000214 mouth Anatomy 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 235000013402 health food Nutrition 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000006225 natural substrate Substances 0.000 description 3
- 231100000957 no side effect Toxicity 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000035943 smell Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 241001411320 Eriogonum inflatum Species 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000001286 intracranial vasospasm Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- YLTGFGDODHXMFB-UHFFFAOYSA-N isoacetovanillon Natural products COC1=CC=C(C(C)=O)C=C1O YLTGFGDODHXMFB-UHFFFAOYSA-N 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- MLIBGOFSXXWRIY-UHFFFAOYSA-N paeonol Natural products COC1=CC=C(O)C(C(C)=O)=C1 MLIBGOFSXXWRIY-UHFFFAOYSA-N 0.000 description 1
- 229910052573 porcelain Inorganic materials 0.000 description 1
- 230000003578 releasing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000002557 soporific effect Effects 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a medicament for curing sedation, sleep and cardiovascular neurogenic headache, and a process for preparation. The invention particularly relates to a dripping pill which contains acetyl gastrodine and a process for preparation. The invention overcomes the shortcomings of the prior dripping pills that pure natural degrees of findings which are used by the prior dripping pills are not high, and chemosynthesis findings which are commonly used are not in food additives catalogs of some countries, and tastes of the dripping pills are worse. The invention is a pharmaceutical preparation whose natural degree is higher, safety is stronger, and side effect is lower.
Description
Technical field
The present invention relates to field of medicaments, specifically one contains drop pill of kind of acegastrodine and preparation method thereof.
Background technology
Acegastrodine can strengthen corticocerebral process of inhibition, presents the brain wave type that maincenter suppresses, and has maincenter tranquilizing soporific effect, and has analgesic activity; But the cerebral blood flow increasing amount is also alleviated cerebral vasospasm; And electrocardiogram, blood pressure there is not obvious influence.List marketing at present tablet only arranged, clinically be used for calmness, sleep peacefully and the cardiovascular nervous headache.
The acegastrodine odorless, bitter in the mouth, insoluble in water, its disintegration of tablet time is long, absorption difference, bioavailability is low, and the supplementary product consumption ratio is big, child, old people, bed patient and dysphagia patients are taken inconvenience, and compliance is poor, have influenced the performance of acegastrodine therapeutical effect.Application number: 03143336.7, the applying date: 2003.9.27, applicant: Nanchang Hongyi Science Co., Ltd, denomination of invention: the patent documentation of acegastrodine drop pill and preparation method thereof provides a kind of dropping pill formulation and preparation method thereof, and this drop pill drug use Polyethylene Glycol and other adjuvants are made drop pill with paeonol; Though this drop pill overcomes the defective of present tablet, has accelerated dissolution rate, there is the not high defective of natural degree of the adjuvant that uses in this drop pill.
Expansion and human back to nature requirement along with the market global range, use the low medicine of toxic and side effects, especially pure natural medical more and more becomes people's first-selection, dropping pill formulation be a kind of have efficient, quick-acting new medicine preparations, it has overcome the shortcoming and deficiency of Chinese medicine preparation in the past, but present dropping pill formulation generally faces following problem: 1, drop pill adjuvant pure natural degree is not high: at present, drop pill substrate adjuvant mostly is synthetic, natural degree is lower, the searching of new alternative substrate adjuvant, the searching of the alternative substrate adjuvant that particularly natural degree is high and preparation technology thereof determine, it is again very difficult thing, because the required preparation condition of at present common possible natural substrates adjuvant succedaneum is very harsh, it all is to influence the key that drop pill prepares molding that adjuvant temperature and drop pill thereof drip the system condition.The too high then viscosity of adjuvant melt temperature is low, and poor plasticity is though the adjuvant melt temperature is crossed lowplastcity by force, but drop pill has shortcomings such as easily sticking ball, distortion, therefore, seek pure natural degree height, and the adjuvant that is suitable for substituting existing drop pill substrate is a very job of hardships.2, the drop pill outlet encounters problems: along with expanding economy, more and more internationalize in market, China is also just making great efforts to adapt to this trend, present Chinese medicine dripping pills preparation as health food, successful export to many countries, but also face many problems at present, because different countries is different to the approval of the selected adjuvant of Chinese medicine dropping pill formulation, especially industrial flourishing Europe, more strict to food adjuvant and medical auxiliary materials, and as the selected chemosynthesis adjuvant (as Polyethylene Glycol) of the dropping pill formulation of health food outlet not in the catalogue of some national food additive, it is very unfavorable that this moves towards the international market to the Chinese medicine dropping pill formulation, becomes the stumbling-block that Chinese medicine enters the international market, therefore, seek the new of one or more, can be particularly important, also very urgent for the substrate adjuvant that the international market is accepted.3, the shortcoming of mouthfeel and onset speed: the mouthfeel of Chinese medicine and preparation thereof is relatively poor to be the big characteristics of one, people when taking some drugs to the frightened of disagreeable taste that medicine had even be better than fear far away to disease, What is more, some patients are because can not overcome the poor taste of Chinese medicine or its preparation or abnormal smells from the patient and abandon the treatment of Chinese medicine, though can improve mouthfeel as medicine being made capsule or sugar coated tablet, reducing stimulates, but disintegration rate prolongs, be unfavorable for the rapid onset of medicine, to some disease, particularly need the disease of the rapid onset of medicine inapplicable.4, the preparation process difficulty of drop pill suitability for industrialized production: in the replacement process of dropping pill formulation adjuvant, determining of the preparation process of its suitability for industrialized production is very difficult something, as the ratio of the melt temperature of substrate adjuvant, the proportioning of dripping system temperature, adjuvant and medicine, dropper bore, condensing agent etc. all are the factors that influence drop pill, therefore, the replacement of substrate and to be suitable for suitability for industrialized production be a job consuming time, as to expend substantial contribution.
In order to change drop pill substrate adjuvant for a long time based on the situation of chemosynthesis adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and can not satisfy more and more that people require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect; Also can solve some problems that Chinese medicine preparation, particularly dropping pill formulation are run in exit procedure, strengthen the competitiveness of international market; The present invention has invented the pure Chinese medicine dripping pills preparation that a kind of toxic and side effects is low, evident in efficacy, moderate, adapt to industrialized great production by a large amount of tests and the research of preparation process.
Summary of the invention
The medicine that the purpose of this invention is to provide a kind of treatment pain with the preparation of new type natural substrate adjuvant and acegastrodine.
Another object of the present invention provides and a kind ofly treats calmness, sleeps peacefully and the preparation method of cardiovascular nervous headache medicine.
The selected substrate adjuvant of the present invention is resulting by a large amount of tests, it is little to have molecular weight, soluble in water, and molten diffusing speed is faster, pure natural degree height, toxic and side effects is low, and can reduce the medicine irritation abnormal smells from the patient, has the oral cavity of improvement acid-base value during the buccal of oral cavity, improve the characteristics of oral cavity smell, the used substrate adjuvant of the present invention is the agent of food sedan-chair flavor, takes that mouthfeel is good, the acceptant characteristics of patient, is the direction of following substrate adjuvant development.
The consumption of drug component of the present invention and the selection of adjuvant thereof also grope to sum up to draw through the inventor in a large number, this medicine is formed and is comprised: acegastrodine, appropriate amount of auxiliary materials, wherein adjuvant comprises filler and plasticity substrate, filler adjuvant wherein is selected from the natural adjuvant of following one or more plant origins: sorbitol, xylitol, lactose, maltose, and they contain the water of crystallization chemical compound; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose;
The adjuvant of preferred drug component of the present invention is following one or more the natural adjuvant of plant origin for the filler adjuvant is selected from: xylitol, lactose; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: starch, arabic gum;
Best substrate adjuvant of the present invention is xylitol and starch, and xylitol is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or be lactose and starch, lactose is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or be xylitol and arabic gum, the ratio of the weight of xylitol and arabic gum is 1: 0.2～1: 0.4.
Adjuvant is 1: 0.1～1: 1 with the ratio of the weight of acegastrodine in the pharmaceutical composition of the present invention;
Adjuvant is 1: 0.1～1: 0.6 with the ratio of the weight of acegastrodine in the preferred pharmaceutical composition of the present invention;
Adjuvant is 1: 0.2～1: 0.4 with the ratio of the weight of acegastrodine in the best pharmaceutical composition of the present invention.
The chemical name of the acegastrodine among the present invention is a 4-methylol benzene-2 ', 3 ', 4 ', and 6 '-four-O-acetyl-β-D-pyranglucoside, molecular formula is C
21H
26O
11, molecular weight is 454.42, structural formula is:
Medicine mesostroma adjuvant of the present invention and amount of drug are than being the scope that allows on the galenic pharmacy, and medicine described here can be that crude drug also can be the effective ingredient extract.
Medicine of the present invention can adopt the preparation of Chinese medicine preparation conventional method; make common any preparation at present; but, preferably adopt following method to be prepared into dropping pill formulation, but this can not limit protection scope of the present invention in order to make each crude drug of this medicine bring into play drug effect better.
The preparation method of medicine of the present invention is as follows:
(a) get acegastrodine, adjuvant is standby;
(b) in appropriate amount of auxiliary materials, add acegastrodine, fully mix, mixture is at 45～115 ℃ of heating and meltings, stir, mixing time is 1～120 minute, insulation, at 45～95 ℃ of temperature following system, dropper bore is 1.0～4.0 millimeters, splash in-15～45 ℃ liquid paraffin, methyl-silicone oil or the vegetable oil, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Further preferred manufacturing procedure is:
The mixture heated melt temperature is 60～85 ℃ in the step (b), and mixing time is 10～30 minutes, and dripping a system temperature and be 60～85 ℃, dropper bore is 1.1～3.5 millimeters, and condensing agent is 0～35 ℃ liquid paraffin or a methyl-silicone oil.
Best preparation method is:
The mixture heated melt temperature is 64～68 ℃ in the step (b), and dripping a system temperature and be 64～68 ℃, dropper bore is 1.2～2.5 millimeters, and condensing agent is 5～25 ℃ a methyl-silicone oil.
More than form when producing and to increase or to reduce according to corresponding ratio, as large-scale production can be unit with kilogram or with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the crude drug material weight proportion constant rate between each composition.
Medicine of the present invention can be determined usage and dosage according to patient's situation in use, but every day 1-3 time, and every day, each crude drug consumption was as the criterion with the state-promulgated pharmacopoeia dosage, was no more than the pharmacopeia ormal weight.
The drop pill that the present invention is prepared, conventional drop pill advantage is simple as preparing except having, steady quality, can make liquid medicine solidification, convenient drug administration, efficient, quick-acting, its biggest advantage is:
1, the selected adjuvant pure natural of the present invention degree height: the substrate adjuvant that employed substrate adjuvant derives from natural plants or originates based on natural plants among the present invention, for example: selected substrate adjuvant is xylitol and starch or lactose and starch or xylitol and arabic gum, this substrate adjuvant has pure natural degree height, toxic and side effects is low, mouthfeel is good, dissolve scattered time limit is short, rapid-action, it is a kind of new medium adjuvant, can be used for substituting present chemosynthesis substrate adjuvant, the drop pill made from this kind adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and more and more can not satisfy people and require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect.
2, some problems in the outlet of solution Chinese medicine: medicine of the present invention also can solve Chinese medicine preparation, some problems of in exit procedure, being run into of dropping pill formulation particularly, solve because different countries, especially the European countries of industry prosperity are to the difference identification of the selected adjuvant of Chinese medicine dropping pill formulation, overcome as the selected adjuvant Polyethylene Glycol of the dropping pill formulation of the health food outlet defective in some national food additive catalogue not, improve the Chinese medicine dripping pills preparation and move towards the international market, strengthen the competitiveness of international market.
3, solve the relatively poor problem of drop pill taste and further improve drug effect speed (dissolve scattered time limit): the medicinal dropping ball made from this kind substrate adjuvant of the present invention, can improve Chinese medicine preparation, the particularly present not good shortcoming of dropping pill formulation taste, improve mouthfeel, more easy for patients to accept, and the drop pill that adopts the selected adjuvant of medicine of the present invention to make has shorter dissolve scattered time limit, makes drug effect faster.
4, higher safety and solve some problems in the drop pill storage process: the selected substrate of the present invention is not only additive, nutrient commonly used in the food industry, and can do medicinal, but do not see that it uses as the drug matrices adjuvant, therefore, with regard to substrate, be perfectly safe, have no side effect, a large amount of evidences, the drop pill that this adjuvant is made can reduce effective ingredient separating out in storage process, the sticking ball of drop pill, easy shortcomings such as moisture absorption deliquescing, but the big production of suitability for industrialized.
To those skilled in the art, technology contents disclosed according to the present invention, those skilled in the art will very clear other embodiment of the present invention, and the embodiment of the invention is only as example.Under the situation of not violating purport of the present invention and scope, can carry out various changes and improvements to the present invention.For example, use different crude drug or extract or active constituents of medicine or effective ingredient and adjuvant provided by the present invention to make various different preparations, particularly drop pill, but as long as use adjuvant of the present invention, all within protection domain of the present invention.
In order to understand the present invention better, the acegastrodine drop pill made from the new substrate of the present invention (according to embodiment 1 preparation, hereinafter to be referred as new acegastrodine drop pill) below; Test explanation advantages of the present invention such as the dissolve scattered time limit of the drop pill of making for the substrate adjuvant with the Polyethylene Glycol (according to application number be: 03143336.7 specific embodiment 1 prepares, hereinafter to be referred as old acegastrodine drop pill), drop pill soft durometer, the sticking ball of drop pill.
Test example 1: dissolve scattered time limit, weight differential contrast experiment's example
In vitro tests
New acegastrodine drop pill and old acegastrodine drop pill compare, and by measuring dissolve scattered time limit, investigate its good releasing effect; By measuring indexs such as the ball method of double differences is different, whether ripe, whether be fit to suitability for industrialized production if investigating its preparation technology.
1. test medication: new acegastrodine drop pill, old acegastrodine drop pill.
2. method and result:
Dissolve scattered time limit: by " method is measured under this item of Chinese pharmacopoeia; The ball method of double differences is different: by " method is measured under this item of Chinese pharmacopoeia.Result of the test sees Table 1.
Three batches in table 1 with new acegastrodine drop pill and old acegastrodine drop pill dissolve scattered time limit, weight differential relatively
Above-mentioned experimental data shows, different being controlled in the pharmacopeia prescribed limit of the ball method of double differences of few, new, the old acegastrodine drop pill of the older acegastrodine drop pill of dissolve scattered time limit of new acegastrodine drop pill.The result of the test explanation, the new acegastrodine drop pill that the new medium adjuvant is made is more conducive to medicine and plays a role in the shortest time, and the ball method of double differences of new, old acegastrodine drop pill is different all to be controlled in the pharmacopeia prescribed limit, but suitability for industrialized production.
Test example 2: the comparative observation of new acegastrodine drop pill and old acegastrodine drop pill soft durometer, the sticking ball of drop pill
Compare by new acegastrodine drop pill and old acegastrodine drop pill, measure indexs such as above-mentioned, investigate its effect.
1. test medication: new acegastrodine drop pill; Old acegastrodine drop pill.
2. method and result:
Get each three batches of new acegastrodine drop pill and old acegastrodine drop pill, be loaded in the porcelain vase respectively, and use the bottle stopper good seal.Putting it into the bottom has in the exsiccator of saturated Nacl (humidity 75%) solution, exsiccator is put into 40 ℃ of drying baker of constant temperature again, and timing sampling is observed situations such as drop pill soft durometer, the sticking ball of drop pill, the results are shown in Table 2.1, table 2.2.
Three batches of old acegastrodine drop pill reserved sample observings of table 2.1 relatively
Table 2.2: three batches of new acegastrodine drop pill and old acegastrodine drop pill character observation are relatively
Table 2.1,2.2 test data show that new acegastrodine drop pill soft durometer changes similar to old acegastrodine drop pill, strong slightly; New acegastrodine drop pill glues the ball variation, firmness change is similar to old acegastrodine drop pill.The result of the test explanation, the sticking ball of new, old acegastrodine drop pill changes, firmness change is similar, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, but suitability for industrialized production.
The specific embodiment
Embodiment 1
(a) get acegastrodine 6.0g, xylitol 18.3g, starch 6.7g is standby;
(b) get xylitol and starch mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 68 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 1.2～2.5 millimeters, splashes in 22～25 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 2
(a) get acegastrodine 20g, lactose 76.9g, starch 23.1g is standby;
(b) get lactose and starch mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 68 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 68 ℃ of temperature following system, dropper bore is 1.2～2.5 millimeters, splashes in 5 ℃ the methyl-silicone oil, makes 3000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 3
(a) get acegastrodine 40g, xylitol 71.4g, arabic gum 28.6g is standby;
(b) get xylitol and arabic gum mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 68 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 64～68 ℃ of temperature following system, dropper bore is 1.2～2.5 millimeters, splashes in 45 ℃ the methyl-silicone oil, makes 4000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 4
(a) get acegastrodine 60g, xylitol 80g, starch 20g is standby;
(b) get xylitol and starch mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 45～70 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 60～70 ℃ of temperature following system, dropper bore is 1.21～2.5 millimeters, splashes in-10～10 ℃ the methyl-silicone oil, makes 5000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 5
(a) get acegastrodine 25g, xylitol 62.5g, starch 37.5g is standby;
(b) get xylitol and starch mix homogeneously, add above-mentioned acegastrodine, mixture stirs at 45～115 ℃ of heating and meltings, and mixing time is 1～30 minute, insulation, at 45～95 ℃ of temperature following system, dropper bore is 1.0～4.0 millimeters, splashes in-20～25 ℃ the vegetable oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 6
(a) get acegastrodine 15g, maltose 100g is standby;
(b) get maltose and add above-mentioned acegastrodine, mixture is at 55～75 ℃ of heating and meltings, stir, mixing time is 5～12 minutes, and insulation is 1.20～3.0 millimeters at 55～75 ℃ of temperature following system, dropper bore, splash in 30～35 ℃ the liquid paraffin, make 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly
Embodiment 7
(a) get acegastrodine 20g, xylitol 80g, cyclodextrin 20g is standby;
(b) get xylitol and cyclodextrin mixing mixing, add above-mentioned acegastrodine, mixture stirs at 45～115 ℃ of heating and meltings, mixing time is 5～20 minutes, and insulation is dripped system 58～70 ℃ of insulations, splash in 10～12 ℃ of liquid paraffin, make 1000 drop pill of drop pill, promptly.
Embodiment 8
(a) get acegastrodine 3.0g, xylitol 19.9g, pregelatinized Starch 8.0g is standby;
(b) get xylitol and pregelatinized Starch mix homogeneously, add above-mentioned acegastrodine, mixture stirs at 60～75 ℃ of heating and meltings, and mixing time is 10～60 minutes, insulation, at 55～65 ℃ of temperature following system, dropper bore is 1.0～3.5 millimeters, splashes in-20～25 ℃ the vegetable oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 9
(a) get acegastrodine 3.5g, lactose 26.6g, starch 3.4g is standby;
(b) get mixing of lactose and starch, add above-mentioned acegastrodine, mixture stirs at 60～85 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 60～85 ℃ of temperature following system, dropper bore is 1.1～3.5 millimeters, splashes in 10～18 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 10
(a) get acegastrodine 4.0g, xylitol 25.5g, arabic gum 3.5g is standby;
(b) get the mixing mixing of xylitol and arabic gum, add above-mentioned acegastrodine, mixture stirs at 60～85 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 60～85 ℃ of temperature following system, dropper bore is 1.1～3.5 millimeters, splashes in 0～8 ℃ the liquid paraffin, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 11
(a) get acegastrodine 4.5g, xylitol 28.0g, alginic acid 2.0g is standby;
(b) get xylitol and alginic acid mixing mixing, add above-mentioned acegastrodine, mixture stirs at 60～85 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 60～85 ℃ of temperature following system, dropper bore is 1.21～3.5 millimeters, splashes in-10～5 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 12
(a) get acegastrodine 5.0g, xylitol 16.6g, sodium carboxymethyl cellulose 14.0g is standby;
(b) get xylitol and sodium carboxymethyl cellulose mix homogeneously, add above-mentioned acegastrodine, mixture stirs at 60～85 ℃ of heating and meltings, and mixing time is 10～20 minutes, insulation, at 60～75 ℃ of temperature following system, dropper bore is 1.5～3.5 millimeters, splashes in 10～18 ℃ the liquid paraffin, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 13
(a) get acegastrodine 5.5g, lactose 24.0g, agar 10.0g is standby;
(b) get lactose and agar mix homogeneously, add above-mentioned acegastrodine, mixture stirs at 60～70 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 62～67 ℃ of temperature following system, dropper bore is 1.2～2.5 millimeters, splashes in 34 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 14
(a) get acegastrodine 6.5g, xylitol 85g, arabic gum 15g is standby;
(b) get xylitol and arabic gum mix homogeneously, add above-mentioned acegastrodine, mixture stirs at 55～85 ℃ of heating and meltings, and mixing time is 5～30 minutes, insulation, at 60～68 ℃ of temperature following system, dropper bore is 1.21～2.5 millimeters, splashes in 20 ℃ the methyl-silicone oil, makes 3000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 15
(a) get acegastrodine 60g, lactose 70g, hydroxypropyl emthylcellulose 20g is standby;
(b) getting lactose and hydroxypropyl emthylcellulose mixes, add above-mentioned acegastrodine, fully mix, mixture is at 64 ℃ of heating and meltings, stir, mixing time is 10～30 minutes, and insulation is 1.2～2.5 millimeters at 65 ℃ of temperature following system, dropper bore, splash in 30 ℃ the methyl-silicone oil, make 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 16
(a) get acegastrodine 7.0g, xylitol 16.0g, methylcellulose 4.5g is standby;
(b) get xylitol and methylcellulose mixing, adding above-mentioned acegastrodine fully mixes, mixture stirs at 60～70 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, at 62～66 ℃ of temperature following system, dropper bore is 1.2～2.5 millimeters, splashes in 5 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 17
(a) get acegastrodine 150g, sorbitol 150g, carboxymethyl starch 50g is standby;
(b) get sorbitol and carboxymethyl starch mixing, adding above-mentioned acegastrodine fully mixes, mixture stirs at 58～78 ℃ of heating and meltings, and mixing time is 20～50 minutes, insulation, at 58～68 ℃ of temperature following system, dropper bore is 1.2～2.5 millimeters, splashes in 0～5 ℃ the methyl-silicone oil, makes 10000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 18
(a) get acegastrodine 55g, xylitol 55g, lactose 5g is standby;
(b) get xylitol and lactose mixing, adding above-mentioned acegastrodine fully mixes, mixture stirs at 60～70 ℃ of heating and meltings, and mixing time is 15～25 minutes, insulation, at 66～66 ℃ of temperature following system, dropper bore is 1.21～2.5 millimeters, splashes in-5～5 ℃ the liquid paraffin, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 19
(a) it is standby to get acegastrodine 5.5g, xylitol 20.5, starch 7.5g;
(b) get xylitol and starch mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 30 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 2.0 millimeters, splashes in 32～35 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 20
(a) get acegastrodine 6.0g, lactose 19.5g, starch 4.5g is standby;
(b) get lactose and starch mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 68 ℃ of heating and meltings, and mixing time is 10 minutes, insulation, at 68 ℃ of temperature following system, dropper bore is 1.2 millimeters, splashes in 40 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 21
(a) get acegastrodine 4.0g, xylitol 20.0g, arabic gum 5.0g is standby;
(b) get xylitol and arabic gum mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 20 minutes, insulation, at 67 ℃ of temperature following system, dropper bore is 2.5 millimeters, splashes in 30 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 22
(a) get acegastrodine 6.0g, xylitol 18.0g, starch 10.0g is standby;
(b) get xylitol and starch mix homogeneously, adding above-mentioned acegastrodine fully mixes, mixture stirs at 70 ℃ of heating and meltings, and mixing time is 25 minutes, insulation, at 65～66 ℃ of temperature following system, dropper bore is 1.21 millimeters, splashes in 6 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 23
(a) get acegastrodine 7.5g, xylitol 26.4g, starch 7.6g is standby;
(b) get xylitol and starch mix homogeneously, add above-mentioned acegastrodine, mixture stirs at 115 ℃ of heating and meltings, and mixing time is 30 minutes, insulation, at 95 ℃ of temperature following system, dropper bore is 1.0 millimeters, splashes in 15 ℃ the vegetable oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Claims (10)
1. drop pill that contains acegastrodine, it is characterized in that this medicine comprises: acegastrodine, appropriate amount of auxiliary materials, wherein adjuvant comprises filler and plasticity substrate, filler adjuvant wherein is selected from the natural adjuvant of following one or more plant origins: sorbitol, xylitol, lactose, maltose, and they contain the water of crystallization chemical compound; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose.
2. the chemical name of acegastrodine as claimed in claim 1 is a 4-methylol benzene-2 ', 3 ', 4 ', and 6 '-four-0-acetyl-β-D-pyranglucoside, molecular formula is C
21H
26O
11, molecular weight is 454.42, structural formula is:
3. the drop pill that contains acegastrodine according to claim 1 is characterized in that wherein filler adjuvant is selected from following one or more the natural adjuvant of plant origin: xylitol, lactose; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: starch, arabic gum.
4. as containing the drop pill of acegastrodine as described in the claim 3, it is characterized in that described adjuvant is xylitol and starch, xylitol is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or be lactose and starch, lactose is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or be xylitol and arabic gum, the ratio of the weight of xylitol and arabic gum is 1: 0.2～1: 0.4.
5. as containing the drop pill of acegastrodine as described in claim 1 or 3, it is characterized in that the adjuvant and the ratio of the weight of acegastrodine are 1: 0.1～1: 1.
6. as containing the drop pill of acegastrodine as described in claim 1 or 3, it is characterized in that the adjuvant and the ratio of the weight of acegastrodine are 1: 0.1～1: 0.6.
7. as containing the drop pill of acegastrodine as described in claim 1 or 3, it is characterized in that the adjuvant and the ratio of the weight of acegastrodine are 1: 0.2～1: 0.4.
8. a preparation method that contains the drop pill of acegastrodine comprises the steps:
(a) get acegastrodine, adjuvant is standby;
(b) in appropriate amount of auxiliary materials, add acegastrodine, fully mix, mixture is at 45～115 ℃ of heating and meltings, stir, mixing time is 1～120 minute, insulation, at 45～95 ℃ of temperature following system, dropper bore is 1.0～4.0 millimeters, splash in-15～45 ℃ liquid paraffin, methyl-silicone oil or the vegetable oil, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
9. as containing the preparation method of the drop pill of acegastrodine as described in the claim 8, it is characterized in that the mixture heated melt temperature is 60～85 ℃, mixing time is 10～30 minutes, dripping the system temperature and be 60～85 ℃, dropper bore is 1.1～3.5 millimeters, and condensing agent is 0～35 ℃ liquid paraffin or a methyl-silicone oil.
10. as containing the preparation method of the drop pill of acegastrodine as described in the claim 9, it is characterized in that the mixture heated melt temperature is 64～68 ℃, dripping a system temperature and be 64～68 ℃, dropper bore is 1.2～2.5 millimeters, and condensing agent is 5～25 ℃ a methyl-silicone oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101299711A CN101194910A (en) | 2006-12-08 | 2006-12-08 | Dropping pills containing acegastrodine and method for preparing the same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101299711A CN101194910A (en) | 2006-12-08 | 2006-12-08 | Dropping pills containing acegastrodine and method for preparing the same |
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|---|---|
| CN101194910A true CN101194910A (en) | 2008-06-11 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104628796A (en) * | 2013-11-07 | 2015-05-20 | 刘力 | Gastrodin medicine, and composition and use thereof |
| CN107325136A (en) * | 2017-08-10 | 2017-11-07 | 昆药集团股份有限公司 | A kind of Acegastrodine compound and preparation method thereof, pharmaceutical composition, preparation and application |
-
2006
- 2006-12-08 CN CNA2006101299711A patent/CN101194910A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104628796A (en) * | 2013-11-07 | 2015-05-20 | 刘力 | Gastrodin medicine, and composition and use thereof |
| CN104628796B (en) * | 2013-11-07 | 2018-09-04 | 刘力 | Gastrodin class drug and combinations thereof and purposes |
| CN107325136A (en) * | 2017-08-10 | 2017-11-07 | 昆药集团股份有限公司 | A kind of Acegastrodine compound and preparation method thereof, pharmaceutical composition, preparation and application |
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Open date: 20080611 |