CN103830244A - Applications of alisol A in preparation of medicine used for treating obesity - Google Patents

Abstract

The invention discloses applications of alisol A in preparation of a medicine used for treating obesity. It is confirmed by animal experiments that: alisol A possesses significant curing effects on obesity models caused by high-fat diet feeding. The medicine provided by the invention is used for treating obesity, possesses exact curative effects, is clear in composition, and is controllable in quality, is based on modern medicine theory, is capable of realizing weight lose and preventing obesity effectively, and is capable of satisfying demands of clinical application.

Description

Application in Alisol A preparation treatment obesity medicine

Technical field

The present invention relates to Alisol A in new purposes pharmaceutically.

Background technology

Along with the raising of living standards of the people, fat sickness rate is also more and more higher.

Obesity is generally divided into two large classes, and a class is the obesity due to illness causing, it is (encephalitis, cerebroma, arthritis or need the chronic disease of long-term steroid) and cause the obesity that endocrine regulation causes because disease, is thisly called symptomatic obesity.This class adiposis patient accounts for 5% left and right of whole fat number.

Another kind of obesity is due to the heat of taking in diet processes, substantially exceeds the heat itself consuming.And make unnecessary fat and other nutriment put aside in vivo formation adipose cell, and cause fat, the people who belongs to this class obesity becomes Simple Obesity, accounts for the more than 90% of obese people's sum.

At present, the medicine for the treatment of obesity, as orlistat, still, this medicine gastrointestinal side effect is obvious, easily causes fatty stool, and even fecal incontinence, causes medication to be restricted.

Chinese patent 200510106261.2 discloses a kind of medicine for the treatment of obesity, and this patent is mainly the antiobesity action that discloses H. seniawinii Maxim., but has the problems such as effective substance basis is indefinite, curative effect on obesity is not remarkable.

Alisol A (AlisolA) is main active in Chinese medicine Rhizoma Alismatis, has had bibliographical information Alisol A to have diuresis, blood fat reducing isoreactivity.But having no the document that Alisol A has antiobesity action publishes.

Summary of the invention

The object of the present invention is to provide the application in Alisol A preparation treatment obesity medicine, the above-mentioned defect existing to overcome prior art, meets the needs of clinical practice.

The invention still further relates to a kind of pharmaceutical composition, comprise the Alisol A of pharmaceutically acceptable carrier and treatment effective dose, Alisol A can share to increase antiobesity action with other slimming medicine.

In described pharmaceutical composition, the weight content of described mixture is 1～99.9%, preferably 50% ~ 99.9%;

Described carrier comprises filler, and as starch, microcrystalline Cellulose or Icing Sugar, excipient, as mannitol, lactose or calcium sulfate, disintegrating agent, as carboxymethyl starch sodium, modified starch or low-substituted hydroxypropyl cellulose; Can adopt method well known in the art, described pharmaceutical composition preparation be become to oral formulations, as tablet, hard capsule, soft capsule, drop pill or granule etc.

In the present invention, described Alisol A source can be to extract and obtain from Waterplantain plant, is preferably the more preferably dry tuber of Notes On Alism At Aceae Rhizoma Alismatis Alisma orientalis (Sam.) Juzep. of Notes On Alism At Aceae Rhizoma Alismatis Alisma orientalis (Sam.) Juzep..In addition, Alisol A can obtain by the method such as semi-synthetic and (or) complete synthesis;

The chemical structure of general formula of described Alisol A is as follows:

Animal experiment proves, pool Alisol A is fed to high lipid food the obese model causing and is had significant therapeutic effect, can be for the preparation of the medicine for the treatment of and prevention of obesity disease, this medicine can put on the patient who needs treatment by oral route, dosage is 20～200mg/ days people, specifically can be determined by doctor according to patient's the state of an illness, age etc.

Described obesity, comprises symptomatic obesity and Simple Obesity, especially Simple Obesity (being the obesity that adipose cell that diet excess intake heat causes increases, increases and causes);

Medicine of the present invention, toxicity is less, is applicable to long-term taking.

Utilization modern medicine theory of the present invention, provides the medicine of a kind of determined curative effect, definite ingredients, quality controllable treatment obesity, can meet the needs of clinical practice.

The present invention discloses first Alisol A and has suppressed Mouse Weight and the fat increase that high fat diet causes, and has the effect of obvious loss of weight, fat-reducing and prevention of obesity.

The specific embodiment

Embodiment 1

The extraction of medical material:

Method 1: get 1 kilogram of the dry tuber of Notes On Alism At Aceae Rhizoma Alismatis Alisma orientalis (Sam.) Juzep., make decoction pieces, extract 2 times each 0.5 hour by 7500ml ethyl acetate backflow.Merge extractive liquid,, decompression and solvent recovery, obtains dark brown extractum 40g.

Method 2: get 3 kilograms of the dry tubers of Notes On Alism At Aceae Rhizoma Alismatis Alisma orientalis (Sam.) Juzep., be ground into coarse granule, by 75% ethanol seepage, merge effusion, decompression and solvent recovery, obtains dark brown extractum 110g.

Method 3: get 2 kilograms of the dry tubers of Notes On Alism At Aceae Rhizoma Alismatis Ailisma orientalis (Sam.) Juzep., be ground into coarse granule, be placed in CO ₂in supercritical extraction instrument, extraction conditions: CO2 pressure is 24～35MPa, extraction temperature is 41～55 ℃, extraction time is 1.5h, obtains dark brown extractum 65g.

Method 4: get 1 kilogram of the dry tuber of Notes On Alism At Aceae Rhizoma Alismatis Alisma orientalis (Sam.) Juzep., make decoction pieces, by 80% methanol 8000ml reflux, extract, 3 times, each 1.0h, merge extractive liquid, liquid, decompression and solvent recovery, obtains dark brown extractum 50g.

Embodiment 2

The preparation of Alisol A:

Take embodiment 1 extractum 10g, upper D101 type macroporous adsorbent resin, after 10 column volumes of 20% ethanol elution, uses 5 column volumes of 70% ethanol elution instead, collects 70% ethanol elution, and decompression and solvent recovery, obtains yellow oil 2g; 2g yellow oil is dissolved in 65% methanol, adopts preparation scale HPLC separate targets compound.Separation condition is: C18 post, and mobile phase is 65% methanol, flow velocity is 50ml/min, detects wavelength 208nm.Obtaining purity is 95%(weight) Alisol A 23-acetas 100mg.

High resolution mass spectrum: m/z:513.35505, C ₃₀h ₅₀o ₅na ⁺[M+Na], its molecular formula is C ₃₀h ₅₀o ₅.

C ¹³nMR (δ): 223.79,139.20,136.95,79.63,74.77,70.69,70.46,58.42,50.73,49.82,48.81,42.00,41.98,38.34,35.54,35.20,34.80,32.13,31.82,30.44,30.03,29.92,29.10,27.37,26.62,26.20,24.59,23.79,21.23,20.89,20.65, with document Rhizoma Alismatis hypolipidemic activity composition Study (Xu Dan, Traditional Chinese Medicinal College of Liaoning's doctorate paper, in May, 2000) in the C of AlisolA ¹³nMR coincide, and determines that this compound is Alisol A.

Embodiment 3

Take Alisol A 10g in embodiment 2, add starch 8g, microcrystalline Cellulose 2g, magnesium stearate 0.2g, mix homogeneously, adopts method well known in the art, makes tablet, capsule or granule.

Embodiment 4

Take embodiment 2 Alisol A 10g, be dissolved in 10ml ethanol, add hydroxypropyl emthylcellulose (HPMC) 4g, in water-bath, stir and fling to solvent, 60 ℃ of dry 2h in vacuum drying oven, pulverize, and cross 20 mesh sieves, and filled capsules obtains capsule.

Embodiment 4

Pharmacodynamic study of the present invention is as follows:

Get the male C57 mice of body weight 24-26g, 30, get at random 10 and give conventional feed as blank group, all the other 20 give high lipid food (cholesterol 1%, Adeps Sus domestica 20%, cholate 0.2%, conventional feed 78.8%), after 6 weeks, measure the body weight of each group of mice, the increase of high lipid food nursing group Mouse Weight, obviously faster than blank group, shows obese model success.20 value mice group, i.e. model control group 10 (pure water), 10 of Alisol A administration groups (Alisol A, 10mg/kg) that high lipid food is fed.Except blank group, all the other each group is all continued to give high lipid food, and gives medicine in every morning 9:30 gavage, and blank group and model control group give the pure water of equivalent.Respectively at after administration 5 weeks days, 12 weeks, to weigh, the data obtained carries out statistical procedures.The results are shown in Table 1, table 2.

The inhibitory action n=10 that table 1 Alisol A raises to Mouse Weight

Note: * represents and blank group compares P<0.05, and * * represents and relatively P<0.01 of blank group;

^▲represent and relatively P<0.05 of model control group, ^{▲ ▲}represent and relatively P<0.01 of model control group, ^{▲ ▲ ▲}represent and relatively P<0.001 of model control group.

As can be seen from Table 1, feed through 6 weeks high lipid foods, Mouse Weight increases faster than blank group, and difference has statistical significance, the success of mark obese model.Treat after 5 weeks through Alisol A, Mouse Weight increase is obviously suppressed, with model control group comparison, significant difference, along with the prolongation for the treatment of time, the antiobesity action of Alisol A is more obvious, in the time of administration 12 weeks, Alisol A administration group mice average weight is 33.9g, and obese model group average weight reaches 40.6g, the two and the comparison of blank group, difference is respectively 2.3g and 9.0g, body weight suppresses to reach (9.0-2.3) ÷ 9.0 × 100%=74.4%, illustrates that Alisol A suppresses body weight increasing action remarkable.

The inhibitory action n=10 that table 2 Alisol A raises to mouse peritoneal fat

Note: * represents and blank group compares P<0.05, and * * represents and relatively P<0.01 of blank group;

^▲represent and relatively P<0.05 of model control group, ^{▲ ▲}represent and relatively P<0.01 of model control group.

As can be seen from Table 2, Alisol A can effectively suppress the abdominal cavity fat increase that high lipid food causes, illustrates that it is good to fat preventive effect.

Conclusion: confirm through above experiment, high lipid food is fed and can successfully be set up mice obese model in 6 weeks, Alisol A has the effect that inhibition Mouse Weight increases, and can effectively suppress the increase of abdominal cavity fat.

Claims (6)

1. the application of Alisol A in preparation treatment obesity medicine.

2. the application of Alisol A in preparation prevention of obesity medicine.

3. application according to claim 1 and 2, is characterized in that, described obesity comprises symptomatic obesity and Simple Obesity.

4. application according to claim 3, is characterized in that, described obesity is Simple Obesity.

5. application according to claim 1 and 2, is characterized in that, described medicine comprises treatment or the Alisol A of prevention effective dose and pharmaceutically acceptable carrier.

6. application according to claim 5, is characterized in that, described medicine is tablet, hard capsule, soft capsule, drop pill or granule.