CN1872252A - Composition of active ingredients of alisma rhizome, and medical application - Google Patents
Composition of active ingredients of alisma rhizome, and medical application Download PDFInfo
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- CN1872252A CN1872252A CN 200510040387 CN200510040387A CN1872252A CN 1872252 A CN1872252 A CN 1872252A CN 200510040387 CN200510040387 CN 200510040387 CN 200510040387 A CN200510040387 A CN 200510040387A CN 1872252 A CN1872252 A CN 1872252A
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- alisol
- rhizoma alismatis
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Abstract
A medical composition is composed of the active components of alismatic rhizome, that is, the alisol A24-acetate and alisol B23-acetate in weight ratio of 1: (0.05-20). It can be used for treating hyperlipemia, fatty liver, atherosclerosis and coronary heart disease.
Description
Technical field
The present invention relates to a kind of Rhizoma Alismatis active ingredient compositions and in pharmaceutically application.Said composition contains Alisol A 24-acetate and alisol B 23-acetas, and two active component total contents are greater than 90%.Said composition can be used for making oral formulations, the fatty liver, atherosclerosis and the coronary heart disease that are used for the treatment of hyperlipidemia and are caused by hyperlipidemia.
Background technology
Be accompanied by the raising of material life, the sickness rate of hyperlipidemia is also more and more higher.The various hearts of Yin Faing, cerebrovascular have become the main chief culprit who threatens middle-aged and elderly people life thus.According to statistics, China has 9,000 ten thousand people to suffer from hyperlipidemia approximately.The cause of disease of hyperlipidemia and pathogenesis complexity involve multiple factor and mechanism.The various hypolipidemic kinds of developing at different onset mechanism are more, and characteristics are respectively arranged.Mainly be divided into two kinds, a kind of based on hypercholesterolemia reducing, low density lipoprotein, LDL, but slightly poor to triglyceride reducing and high density lipoprotein increasing, as statins; Another kind of based on triglyceride reducing, as Elasterin.But do not have a kind of so far to all effective medicine of all lipid disorders.
Rhizoma Alismatis mainly originates in provinces such as Fujian, Sichuan, Jiangxi, is perennial limnocryptophyte, existing polyphyly cultivation.The main effect of Rhizoma Alismatis is used for dysuria, edema distension, the oliguria of having loose bowels, dizziness due to fluid-retention, the puckery pain of pyretic stranguria.
Every oral Rhizoma Alismatis crude drug of experimental atherosclerosis rabbit, the result shows that Rhizoma Alismatis reduces serum total cholesterol and the triglyceride effect is remarkable, promotes the Serum HDL-C level to raise, and suppresses the generation of aortic tunica intima speckle significantly.The oral Rhizoma Alismatis liquid of experimental hyperlipemia rat, the result shows that Rhizoma Alismatis reduces serum total cholesterol and LDL-C effect highly significant, and has effects such as antiplatelet aggregation, antithrombotic formation and promotion plasmin activity.Alisol extract animal experiment shows that the tentative hyperlipidemia of rabbit is had therapeutical effect and lipotropy, and its effect is better than Fructus Crataegi, Cortex Lycii.
The chemical constituent of Rhizoma Alismatis is mainly and contains multiple tetracyclic triterpenoids compound, comprise alisol (Alisol) A, B, C and Alisol A 24-acetate (Alisol A monoacetate), alisol B 23-acetas (Alisol B monoacetate), alisol C acetas (Alisol Cmonoacetate), epialisol A (Epi-alisol A) also contain a spot of choline, lecithin, volatilization wet goods.
Prove that through pharmacological evaluation the active component of blood fat reducing is a tetracyclic triterpene in the Rhizoma Alismatis.And the chemical constituent of Chinese medicine and complexity thereof, in order to guarantee the curative effect of Rhizoma Alismatis extract, content of effective in the necessary clear and definite Rhizoma Alismatis extract.
Summary of the invention:
The objective of the invention is to use the modern medicine theory,, provide the Rhizoma Alismatis active ingredient compositions of a kind of definite ingredients, quality controllable, determined curative effect through the blood fat reducing animal model test.
Another object of the present invention is to said composition and can be used for making oral formulations.
Another purpose of the present invention is that said composition can be used for preparing the application in the treatment high blood cholesterol drug.
The present invention also aims to said composition and can be used for preparing treatment by the application in fatty liver, atherosclerosis and the medicaments for coronary disease of hyperlipidemia initiation.
Purpose of the present invention can reach by following measure:
The present invention contains Alisol A 24-acetate and alisol B 23-acetas activity extract, and the two total content is greater than 90%, and its weight ratio is 1: 0.05～20, and preferred weight ratio is 1: 0.5～5, and its optimum weight ratio is 1: 1.
The present invention contains the Pharmaceutical composition that above-mentioned Rhizoma Alismatis active extract composition and one or more pharmaceutical excipients are made.
The extraction of Alisol A 24-acetate and alisol B 23-acetas source can be the Waterplantain plant among the present invention, this platymiscium in state-owned 6 kinds (" Chinese Plants will the 8th volume "), be preferably Alismataceae plant Rhizoma Alismatis Alisma orientalis (Sam.) the Juzep. dry tuber of Alismataceae plant Rhizoma Alismatis Alisma orientalis (Sam.) Juzep. more preferably.
The present invention has and rationally utilizes Rhizoma Alismatis resource, clear and definite effective ingredient and content, can be used for making tablet, capsule, can be used for making the medicine of treatment hyperlipidemia, and make treatment by the application in fatty liver, atherosclerosis and the medicaments for coronary disease of hyperlipidemia initiation.
Pharmacodynamic study of the present invention is as follows:
Get the SD male rat of body weight 150-180g, 70, be divided into 7 groups at random, and blank group, model control group, positive controls (Lip river cut down him left alone without help 8mg/kg), A group (Alisol A 24-acetate, 24mg/kg), B organizes (alisol B 23-acetas, 24mg/kg), C group (Alisol A 24-acetate+alisol B 23-acetas, 1: 1,24mg/kg), D organizes (Alisol A 24-acetate+alisol B 23-acetas, 1: 2,24mg/kg).The blank group gives conventional feed, all the other six groups give high lipid food (cholesterol 2%, bovine bile 0.5%, propylthiouracil 0.2%, Adeps Sus domestica 10%, normal feedstuff 87.3%), normal feedstuff group is respectively got 10 in the high lipid food group after 15 days, eye socket is got blood (getting the preceding animal fasting of blood 16 hours), leave standstill and solidify, centrifugal, separation of serum is measured T-CHOL (TC), serum triglycerides (TG), high density lipoprotein (HDL-C), low density lipoprotein, LDL (LDL-C) with enzyme process through ultraviolet spectrophotometer.
Medication:
Stop high lipid food from the 16th day and feed, all use normal diet instead.Respectively organizing simultaneously rat irritates stomach respectively give corresponding medicine every afternoon, be that positive controls (Lip river cut down him left alone without help 8mg/kg), A group (24mg/kg), B group (24mg/kg), C group (24mg/kg), D are organized (24mg/kg), blank group and model control group give the 0.5%CMC-Na of equivalent.After the administration 14 days, fasting 16 hours is weighed, and femoral artery is got blood, gets liver and weighs and make liver homogenate, measures serum TC, TG, HDL-C, LDL-C and liver TC, TG, and the gained data are carried out statistical procedures.
Lipid determination
Blood leaves standstill and solidifies, centrifugal (2000pm * 20min), separation of serum, reference reagent box description is measured TC, TG, HDL-C, LDL-C with enzyme process through ultraviolet spectrophotometer, the results are shown in Table 1.
Table 1 pair serum triglycerides (TG), T-CHOL (TC), high density lipoprotein (HDL-C),
The influence of low density lipoprotein, LDL (LDL-C) (X ± S) (n=10)
| Dosage (mg/kg) | Unit: mmol/L | ||||
| TG | TC | HDL-C | LDL-C | ||
| His left alone without help A B C D is cut down in model group normal group Lip river | 8 24 24 24 24 | 0.38±0.12 0.22±0.09** 0.26±0.05** 0.24±0.08** 0.46±0.09 0.25±0.07** 0.27±0.09** | 8.89±0.58 5.41±1.31** 6.07±0.56** 7.23±1.65** 6.99±1.29** 7.05±1.52** 7.12±1.47** | 0.48±0.28 1.56±0.90** 1.35±0.78** 1.27±0.30** 0.85±0.56 1.19±0.45** 1.06±0.43 | 6.77±1.31 3.97±1.16** 4.15±0.94** 5.04±1.94 4.68±0.82** 4.83±1.27** 4.74±1.03** |
Annotate:
*P＜0.01, each group all compares with model control group
Table 1 explanation: A medicine 24mg/kg dosage group can extremely significantly reduce serum triglycerides, serum total cholesterol, high density lipoprotein increasing, and it is not obvious to reduce low density lipoprotein, LDL; B medicine 24mg/kg dosage group can extremely significantly reduce serum total cholesterol, serum low-density LP, and it is not obvious to reduce serum levels of triglyceride, and high density lipoprotein increasing is not obvious.C medicine 24mg/kg dosage group can extremely significantly reduce serum triglycerides, T-CHOL, low density lipoprotein, LDL, and serum high-density LP extremely significantly raises; D medicine 24mg/kg dosage group can extremely significantly reduce serum triglycerides, T-CHOL, low density lipoprotein, LDL, and the rising serum high-density LP is not obvious.The C medicine is than independent A medicine, and the B medicine is effective.
Liver fat is measured
Every rat is got 100mg lobus sinister hepatic tissue and adds the 1ml0.9% normal saline, wears into homogenate, centrifugal (gets supernatant behind the 3000pm * 15min), measures liver TG, TC by last method again, the results are shown in Table 2.
The influence of table 2 pair liver homogenate triglyceride (TG), T-CHOL (TC)
( X±S)(n＝10)
| Dosage (mg/kg) | Unit: mmol/L | ||
| TG | TC | ||
| His left alone without help A B C D is cut down in model group normal group Lip river | 8 24 24 24 24 | 1.45±0.21 1.10±0.19** 1.12±0.28** 1.19±0.12** 1.42±0.27 1.20±0.17** 1.25±0.19 | 2.51±0.17 2.04±0.12** 2.22±0.15** 2.30±0.16** 2.34±0.14 2.31±0.15** 2.33±0.24 |
Annotate:
*P＜0.01, each group all compares with model control group
Table 2 explanation: A medicine 24mg/kg dosage group can extremely significantly reduce liver homogenate triglyceride, T-CHOL.B drug effect fruit is not obvious.C medicine 24mg/kg dosage group can extremely significantly reduce liver homogenate triglyceride, T-CHOL, high density lipoprotein increasing; D medicine 24mg/kg dosage group DeGrain.A medicine and C drug effect fruit are quite.B medicine and D drug effect fruit are not obvious.
Conclusion: have this experiment to reach a conclusion, A medicine and B medicine respectively have characteristics, and the A medicine is with triglyceride reducing, T-CHOL, and high density lipoprotein increasing is main, and it is relatively poor to reduce low density lipoprotein, LDL; The B medicine is to reduce low density lipoprotein, LDL, and triglyceride reducing and high density lipoprotein increasing are not obvious.And the combination C medicine of A medicine and B medicine has played complementary effect, aspect six indexs better curative effect is being arranged all, and is more effective with A medicine or B medicine than single.So the C medicine has the obvious treatment effect to the rat high blood lipid model.
The specific embodiment
Embodiment 1:
The preparation of medical material extractum:
Method a: get 2 kilograms of pulverizing of dry tuber of Alismataceae plant Rhizoma Alismatis Alisma orientalis (Sam.) Juzep., with 4 liters of chloroform reflux, extract, 2 times, each 3 hours.Merge extractive liquid, reclaims solvent and obtains oily extractum 87 grams.
Method b: get 2 kilograms of pulverizing of dry tuber of Alismataceae plant Rhizoma Alismatis Alisma orientalis (Sam.) Juzep., the ethanol percolation with 80% reclaims ethanol, grease 94 grams that obtain.
Method c: the dry tuber of getting Alismataceae plant Rhizoma Alismatis Alisma orientalis (Sam.) Juzep. is pulverized, cross 20 mesh sieves, take by weighing 4 kilograms in medicated powder, putting carbon dioxide supercritical fluid extraction 10L extracts in the bucket, extraction conditions: pressure carbon dioxide is 20～45MPa, 46～49 ℃ of extraction temperature, obtain grease 150 grams at 2.5 hours extraction time.
Method d: get 1 kilogram of decoction pieces of dry tuber of Alismataceae plant Rhizoma Alismatis Alisma orientalis (Sam.) Juzep., use methanol eddy to extract, methanol usage 3000ml extracts 3 times, each 3 hours, obtains grease 45 grams.
Method e: get 1 kilogram of decoction pieces of dry tuber of Alismataceae plant Rhizoma Alismatis Alisma orientalis (Sam.) Juzep., use 90% ethanol alcohol reflux to extract, methanol usage 3000ml extracts 3 times, each 3 hours, obtains grease 50 grams.
Embodiment 2:
The preparation of alisol B 23-acetas:
Method a: take by weighing embodiment 1 oily extractum 100 grams, last silicagel column (500 gram) is with behind petroleum ether, ethyl acetate (10: the 1) eluting, again with petroleum ether, ethyl acetate (10: 3) eluting, 200mL is a stream part, detect with TLC, collect the target flow point, get crystallization 0.8g.Obtain 0.5 gram crystallization with the petroleum ether-ethyl acetate recrystallization.Be accredited as alisol B 23-acetas.
Method b: take by weighing embodiment 1 oily extractum 100 gram, last aluminium sesquioxide (500 restrain) post with petroleum ether, chloroform (20: 1) eluting after, again with petroleum ether, chloroform (10: 1) eluting, 200mL is a stream part, detect with TLC, collect the target flow point, get crystallization 0.7g.After recrystallizing methanol, obtain 0.5 gram crystallization, be accredited as alisol B 23-acetas.
Embodiment 3:
The preparation of Alisol A 24-acetate:
Method a: after among the embodiment 2 method a petroleum ether, ethyl acetate (10: 3) eluting being finished, with petroleum ether, ethyl acetate (10: 5) eluting, detect again, collect the target flow point with TLC, crystallization 0.4g, the petroleum ether-ethyl acetate recrystallization gets 0.3 gram.Be accredited as Alisol A 24-acetate.
Method b: after among the embodiment 2 method b petroleum ether, chloroform (10: 1) eluting being finished,, detect, collect the target flow point with TLC again with petroleum ether, chloroform (10: 3) eluting, crystallization 0.4g, with obtaining 0.3 gram crystallization after the recrystallizing methanol.Be accredited as Alisol A 24-acetate.
Embodiment 4:
Alisol B 23-acetas+Alisol A 24-acetate preparation of compositions
Method a: the product that embodiment 2 and embodiment 3 are taken mixed according to 1: 1, obtained Rhizoma Alismatis and extracted compositions.
Method b: the product that embodiment 2 and embodiment 3 are taken mixed according to 1: 2, obtained Rhizoma Alismatis and extracted compositions.
Method c: take by weighing embodiment 1 oily extractum 100 grams, last silicagel column (500 gram) is with behind petroleum ether, ethyl acetate (10: the 1) eluting, again with petroleum ether, ethyl acetate (10: 5) eluting, detect with TLC, collect target components, obtain grease 5 grams, the reuse petroleum ether-ethyl acetate is recrystallization repeatedly, obtains solid 2 grams.HPLC detects, and contains alisol B 23-acetas+Alisol A 24-acetate＞90%, and ratio is 1.2: 1.
Method d: take by weighing embodiment 1 oily extractum 100 grams, last aluminium sesquioxide (500 gram) post with petroleum ether, chloroform (20: 1) eluting after, again with petroleum ether, chloroform (10: 3) eluting, detect with TLC, collect target components, obtain grease 5.5 grams, the reuse petroleum ether-ethyl acetate is recrystallization repeatedly, obtains solid 1.8 grams.HPLC detects, and contains alisol B 23-acetas+Alisol A 24＞90%, and ratio is 1.1: 1.
Embodiment 5:
The preparation of Rhizoma Alismatis active ingredient compositions: compositions 50 grams that embodiment 4 is taken add starch 50g, mix homogeneously, the back filled capsules or make tablet of granulating.
Embodiment 6:
The preparation of Rhizoma Alismatis active ingredient compositions: compositions 40 grams with embodiment 4 takes add starch 60g granulation back filled capsules or make tablet.
Claims (8)
1. Rhizoma Alismatis active extract composition, it is characterized in that said composition contains Alisol A 24-acetate and alisol B 23-acetas, and two active component total contents are greater than 90%, and the weight ratio of Alisol A 24-acetate and alisol B 23-acetas is 1: 0.05～20 in the said composition.
2. Rhizoma Alismatis active extract composition according to claim 1 is characterized in that the weight ratio of Alisol A 24-acetate and alisol B 23-acetas is 1: 0.5～5 in the said composition.
3. Rhizoma Alismatis active extract composition according to claim 2 is characterized in that the weight ratio of Alisol A 24-acetate and alisol B 23-acetas is 1: 1 in the said composition.
4. pharmaceutical composition, it contains the defined Rhizoma Alismatis active extract composition of claim 1 and one or more pharmaceutical excipients.
5. Rhizoma Alismatis active extract composition according to claim 4 is characterized in that described Pharmaceutical composition is an oral formulations.
6. Rhizoma Alismatis active extract composition according to claim 5 is characterized in that described Pharmaceutical composition is tablet, capsule.
7. the application of the active extract composition of Rhizoma Alismatis in preparation treatment hyperlipidemia medicine.
8. the application of the active extract composition of Rhizoma Alismatis in fatty liver, atherosclerosis and medicaments for coronary disease that the preparation treatment is caused by hyperlipidemia.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103845340A (en) * | 2012-12-07 | 2014-06-11 | 上海现代药物制剂工程研究中心有限公司 | Application of alisol A 24-acetate in preparation of medicaments for preventing and treating arterial diseases |
| CN103845341A (en) * | 2012-12-07 | 2014-06-11 | 上海现代药物制剂工程研究中心有限公司 | Application of alisol A 23-acetate in preparation of medicaments for preventing and treating arterial diseases |
| CN103908453A (en) * | 2013-01-04 | 2014-07-09 | 上海现代药物制剂工程研究中心有限公司 | Application of alisol G in preparation of medicine for preventing and treating obesity |
| CN104434930A (en) * | 2014-11-14 | 2015-03-25 | 南京中医药大学 | Composition containing 24-acetyl alisol A and 23-acetyl alisol B and application thereof in regulation of blood fat and preparation of HMG-CoA inhibitor |
| CN104622882A (en) * | 2015-01-12 | 2015-05-20 | 许波 | Pharmaceutical composition for treating atherosclerosis and application of pharmaceutical composition |
| CN104622883A (en) * | 2015-01-12 | 2015-05-20 | 许波 | Pharmaceutical preparation for treating atherosclerosis and preparation method of pharmaceutical preparation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1283653C (en) * | 2003-04-29 | 2006-11-08 | 浙江万马药业有限公司 | Oriental waterplantain rhizome sterol extract and its preparing method and quality control method |
-
2005
- 2005-06-03 CN CNB2005100403874A patent/CN100353974C/en not_active Expired - Fee Related
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103845340A (en) * | 2012-12-07 | 2014-06-11 | 上海现代药物制剂工程研究中心有限公司 | Application of alisol A 24-acetate in preparation of medicaments for preventing and treating arterial diseases |
| CN103845341A (en) * | 2012-12-07 | 2014-06-11 | 上海现代药物制剂工程研究中心有限公司 | Application of alisol A 23-acetate in preparation of medicaments for preventing and treating arterial diseases |
| CN103845340B (en) * | 2012-12-07 | 2016-08-03 | 上海现代药物制剂工程研究中心有限公司 | Alisol A 24-acetas prevents and treats the application in arterial disease medicine in preparation |
| CN103908453A (en) * | 2013-01-04 | 2014-07-09 | 上海现代药物制剂工程研究中心有限公司 | Application of alisol G in preparation of medicine for preventing and treating obesity |
| CN103908453B (en) * | 2013-01-04 | 2016-04-06 | 上海现代药物制剂工程研究中心有限公司 | Alisol G is preparing the application prevented and treated in obesity medicine |
| CN104434930A (en) * | 2014-11-14 | 2015-03-25 | 南京中医药大学 | Composition containing 24-acetyl alisol A and 23-acetyl alisol B and application thereof in regulation of blood fat and preparation of HMG-CoA inhibitor |
| CN104434930B (en) * | 2014-11-14 | 2017-06-09 | 南京中医药大学 | Composition comprising 24 acetylalisol A and 23 acetylalisol B and its in Adjust-blood lipid, the application prepared on HMG CoA inhibitor |
| CN104622882A (en) * | 2015-01-12 | 2015-05-20 | 许波 | Pharmaceutical composition for treating atherosclerosis and application of pharmaceutical composition |
| CN104622883A (en) * | 2015-01-12 | 2015-05-20 | 许波 | Pharmaceutical preparation for treating atherosclerosis and preparation method of pharmaceutical preparation |
| CN104622882B (en) * | 2015-01-12 | 2017-12-05 | 青岛市中心医院 | For treating the medical composition and its use of atherosclerosis |
| CN104622883B (en) * | 2015-01-12 | 2017-12-05 | 青岛市中心医院 | Pharmaceutical preparation for treating atherosclerosis and preparation method thereof |
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| CN100353974C (en) | 2007-12-12 |
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