CN104739840A - Novel use of asiatic acid in preparation of drugs for preventing and treating hyperlipidemia and fatty liver - Google Patents
Novel use of asiatic acid in preparation of drugs for preventing and treating hyperlipidemia and fatty liver Download PDFInfo
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Abstract
The invention relates to the field of drug research and development and discloses a use of asiatic acid in preparation of drugs for preventing and treating hyperlipidemia and non-alcoholic fatty liver disease. Correspondingly, the invention also discloses a drug for preventing and treating of hyperlipidemia and a drug for preventing and treating fatty liver. The drugs contain an effective dose of asiatic acid. The drugs respectively have obvious effects of reducing blood fat and protecting liver, can be used for treatment and prevention of hyperlipidemia and non-alcoholic fatty liver disease caused by a plurality of reasons and have substantial treatment effects.
Description
Technical field
The present invention relates to Field of Drug Discovery, be specifically related to the novelty teabag that asiatic acid prepares hyperlipidemia prevention and therapy medicine and fatty liver prevention and therapy medicine, and related drugs.
Background technology
The infringement of hyperlipidemia to health is a concealment process increased the weight of slowly, gradually.Along with rising and the prolongation of dyslipidemia time of blood fat, the various diseases such as atherosclerosis, coronary heart disease, hypertension, diabetes, apoplexy, fatty liver can be caused.Hyperlipemia sickness rate in middle-aged and elderly people is high, and along with China steps into aging society, the sickness rate of hyperlipemia increases day by day, becomes an important content in China's Healthcare gradually.
Along with the continuous increase of hyperlipidemia population, the demand of blood lipid-lowering medicine is constantly expanded, in the best-selling 200 kinds of medicines in the whole world in 2003,8 kinds are had to be blood fat-reducing product: global sales ranks the first, the medicine of second is all blood fat reducing preparation, be respectively the atorvastatin of Pfizer and the simvastatin of Merck, and hypolipidemic also maintains the quick growing trend of annual 9%.Therefore, research and develop novel blood lipid-lowering medicine and there is great social value and economic benefit.
Liver plays central hub effect in lipid metabolism, and he had both participated in the metabolism of triglyceride, also participates in the metabolism of cholesterol.The various hyperlipemia of fatty liver patient is all visible, and what relation was the closest is hypertriglyceridemia, often with fat and diabetes.High fat, sweet food and ethanol can bring out hyperlipemia and fatty liver simultaneously.Epidemiological investigation shows, and hyperlipemia is the important risk factor of fatty liver.The hyperlipidemia patient of 20-92% merges fatty liver.The various hyperlipemia of Patients with Fatty Liver is all visible.What relation was the closest is high TG mass formed by blood stasis.On the one hand, hyperlipemia can increase because hepatocyte TG synthesizes, and causes TG to pile up in hepatocyte, thus causes fatty liver.
Herba Centellae is the dry herb of Umbelliferae Centella plant Centella asiatica (Centella asiatica L.Urban).Slightly cool in nature, mildly bitter flavor, sweet.Have heat-clearing and toxic substances removing, eliminating stasis to stop pain, removing heat from blood promote the production of body fluid, diuresis effect, be called as the long-lived medicine of Asians.114 kinds of one that can be used in the article of health food in February, 2002 Ministry of Public Health " notice of further specification healthy food material management ".It is reported, Herba Centellae has antiinflammatory, promotes the effect of wound healing, simultaneously can Improving memory, anti-oxidation stress and block the effect of hepatic fibrosis.Herba Centellae total glycosides has the effect reducing lipid of mice.
Summary of the invention
The object of the invention is to novelty teabag and the related drugs of open asiatic acid prevention and therapy hyperlipemia and non-alcoholic fatty liver disease.
First the present invention discloses asiatic acid and is preparing the purposes in prevention and therapy hyperlipidemia and fatty liver medicament.
Preferably, described asiatic acid as sole active ingredient for the preparation of prevention and therapy hyperlipidemia and fatty liver medicament.
Fatty liver of the present invention is non-alcoholic fatty liver disease.
Asiatic acid is used for the treatment of the Be very effective of hyperlipidemia and non-alcoholic fatty liver disease.
Second aspect present invention discloses a kind of medicine of prevention and therapy hyperlipemia, the asiatic acid containing treatment effective dose.
In the medicine of described prevention and therapy hyperlipemia, asiatic acid is the sole active ingredient of this medicine.
The invention also discloses a kind of medicine for the treatment of non-alcoholic fatty liver disease, the asiatic acid containing treatment effective dose.
In the medicine of described treatment non-alcoholic fatty liver disease, asiatic acid is the sole active ingredient of this medicine.
Preferably, pharmaceutically acceptable carrier is also comprised in described medicine.
Pharmaceutically acceptable carrier is various pharmaceutically conventional adjuvant and/or excipient, include, but is not limited to saccharide (as lactose, dextrose plus saccharose), starch (as corn starch and potato starch), cellulose and its derivates is (as sodium carboxymethyl cellulose, ethyl cellulose and methylcellulose), tragacanth gum powder, Fructus Hordei Germinatus, gelatin, Talcum, kollag (as stearic acid and magnesium stearate), calcium sulfate, vegetable oil, as Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, Oleum sesami, olive oil, Semen Maydis oil and cupu oil, polyhydric alcohol is (as propylene glycol, glycerol, Sorbitol, mannitol and Polyethylene Glycol), alginic acid, emulsifying agent is (as Tween, polyoxyethylene castor oil), wetting agent (as sodium lauryl sulfate), coloring agent, flavoring agent, tablet agent, stabilizing agent, antioxidant, antiseptic, apirogen water, isotonic saline solution and phosphate buffer etc., this carrier can improve stability, the activity and biological effectiveness etc. of formula as required.
Preferably, the dosage form of described medicine is selected from tablet, pill, capsule, granule or oral liquid.Namely the present invention adopt pharmaceutic adjuvant conveniently technique be prepared into tablet, pill, capsule, granule or oral liquid.
Preferably, the medicine for the treatment of non-alcoholic fatty liver disease of the present invention, and prevent and treat in hyperlipidemia, the dosage of asiatic acid is less than 100mg/(kg body weight).
Medicine of the present invention has obvious blood fat reducing and liver-protective effect, can be used for the prevention and therapy of hyperlipidemia that many reasons causes and non-alcoholic fatty liver disease, has significant therapeutic effect.
Accompanying drawing explanation
Fig. 1: Asiatic acid is on the impact of hyperlipemia model lipid of mice
Fig. 2: asiatic acid on the impact of hyperlipi demic hamsters blood lipid metabolism (n=8,
compared with model control group, * P<0.05, * * * P<0.001)
Fig. 3: asiatic acid is on the impact of hyperlipi demic hamsters liver function index (n=8, x ± s, compared with model control group, * P<0.05, * * P<0.01, * * * P<0.001)
Fig. 4: asiatic acid is on the impact (n=8 of TC, TG, GSH-PX and SOD in hyperlipi demic hamsters hepatic tissue, x ± s, compared with model control group, * P<0.05, * P<0.01, * * * P<0.001)
Fig. 5: the HE coloration result (A: Normal group of gold suslik liver frozen section; B: hyperlipemia model matched group; C: Xuezhikang group; D:AA_L group; E:AA_H group)
Detailed description of the invention
Set forth this utility model further below in conjunction with specific embodiment, should be understood that embodiment is only not used in restriction protection domain of the present utility model for illustration of this utility model.
By acute sieve medicine result display; asiatic acid can reduce the blood lipid level of acute hyperlipemia mice; further by the foundation of Golden Hamster hyperlipemia model and the intervention of asiatic acid variable concentrations administration; inquiring into blood fat reducing and the liver protection of asiatic acid, laying the foundation for finding new lipid-regulation medicine.
Test example 1 asiatic acid is on the impact of acute hyperlipemia
1, experimental technique
1) laboratory animal and reagent
Kunming mouse 24, male, counterpoise 25 grams, purchased from Shanghai Slac Experimental Animal Co., Ltd.; Credit number: SCXK (Shanghai) 2007-0005.
Triton1339, purchased from SIGMA company
Fenofibrate, purchased from SIGMA company
Asiatic acid, purchased from the natural pharmaceutcal corporation, Ltd of Guangxi Chang Zhou
2) animal processing method
Male mice in kunming, normal illumination, raising temperature 18 ~ 25 DEG C, humidity 40 ~ 60%, give normal diet, after adaptability of freely drinking water raises one week, be divided into 4 groups all at random, often organize 6, be respectively 1) Normal group, 2) acute hyperlipemia model control group, 3) fenofibrate group, 4) asiatic acid group (100mg/kg).
Except Normal group, test each group (acute hyperlipemia model control group, fenofibrate group, asiatic acid group) respectively at the same day 16 time lumbar injection Triton1339400mg/kg, and give normal group normal saline, model group normal saline, fenofibrate group 100mg/kg fenofibrate, asiatic acid group 100mg/kg asiatic acid respectively in the mode of gavage simultaneously; In secondary 8 time, (after 16 hours) whole broken end gets blood, measures mice serum TC, TG.
2, results and analysis
Chmice acute hyperlipemia 16 hours point Blood Lipid situation is shown in Fig. 1, and interpretation is as follows:
1. as can be seen from Figure 1, hyperlipidemia model treated animal TC, TG equal significance compared with Normal group raises, and p<0.001 illustrates modeling success.
2. fenofibrate group is compared with hyperlipidemia model group, and TC, TG all have significance to decline (p<0.001 and p<0.001), illustrate that positive control drug fenofibrate is remarkable for acute hyperlipemia model lipid-lowering effect.
3. asiatic acid (100mg/kg) is compared with hyperlipidemia model group, TC, TG all have obvious decline, p<0.01 and p<0.001, all has significant difference, illustrates that asiatic acid is remarkable for acute hyperlipemia model lipid-lowering effect.
Passable as apparent from above-mentioned experimental result, asiatic acid obviously can reduce the content of TC, TG in chmice acute hyperlipemia serum, has effect of blood fat reducing.
Test example 2 asiatic acid is on the impact of Golden Hamster Diet hyperlipemia
1, experimental technique
1.1 laboratory animals and reagent
Golden Hamster (golden hamster) 40, male, counterpoise 90 grams, purchased from pine connection laboratory animal field, Shanghai Songjiang district, credit number: SCXK (Shanghai) 2007-0011.
Xuezhikang, purchased from Beijing WBL Peking University Biotech Co., Ltd, batch number: 20130404
Asiatic acid, purchased from Guangxi Chang Zhou natural drug company limited
1.2 animal processing methods
Golden Hamster, temperature 23 ± 1 DEG C, humidity: 40 ~ 60%, natural lighting, freely drink water, ad lib normal diet 1 week, is divided into 5 groups at random, often organizes 8, be designated as 1. Normal groups respectively, 2. hyperlipemia model matched group, 3. Xuezhikang group (being designated as Xzk), 4. asiatic acid low dose group (being designated as AA_L), 5. asiatic acid high dose group (being designated as AA_H).
Except Normal group gives normal diet, all the other groups all give high lipid food.High lipid food formula is: (to pull together company of feed corporation,Ltd purchased from Beijing Australia of section, batch number: 130532318) 88%, Adeps Sus domestica 10%, cholesterol 2%, feeds 4 weeks normal diet.
Administration by the following method:
1) Normal group: at 10 in every day in the morning gives 5% tween solution, mode: gavage.
2) hyperlipemia model matched group: at 10 in every day in the morning gives 5% tween solution, mode: gavage.
3) Xuezhikang group: at 10 in every day in the morning is administered once, dosage 250mg/kg, mode: gavage.
4) AA_L group: at 10 in every day in the morning is administered once, dosage 8mg/kg, mode: gavage.
5) AA_H group: at 10 in every day in the morning is administered once, dosage 16mg/kg, mode: gavage.
Successive administration is after 4 weeks according to the method described above, and all animal hearts get blood, take off liver organization, measures serum total cholesterol, triglyceride, low density lipoprotein, LDL LDL, high density lipoprotein HDL, glutamate pyruvate transaminase GPT, glutamic oxaloacetic transaminase, GOT GOT; Liver Superoxide Dismutase Activity SOD, glutathion peroxidase GSH-PX, make liver frozen section, and HE dyes.
2, results and analysis
2.1 asiatic acids are on the impact of hyperlipi demic hamsters body weight, liver weight and liver coefficient
Experimental result, in table 1, contrasts with blank group, and model group Golden Hamster body weight, liver weigh and liver coefficient all obviously raises (P<0.01, P<0.001, P<0.001).Successive administration is after 4 weeks, and Xuezhikang and asiatic acid low dose group, asiatic acid high dose group Golden Hamster body weight significance reduce (P<0.01, P<0.05, P<0.01).Xuezhikang, asiatic acid low dosage, asiatic acid high dose group all significantly can alleviate liver heavy (P<0.001), and asiatic acid two dosed administration groups all can reduce the liver coefficient (P<0.001) of hyperlipi demic hamsters.
The impact of table 1 asiatic acid and liver coefficient heavy on hyperlipi demic hamsters body weight, liver (n=8,
)
Note: * p<0.05.**p<0.01, * * * p<0.001 is compared with model group
2.2 asiatic acids are on the impact of hyperlipi demic hamsters blood lipid metabolism
The experimental result of asiatic acid to hyperlipi demic hamsters Changes of Lipids Metabolism is shown in Fig. 2.Compared with blank group, serum TC, TG and LDL of model control group Golden Hamster all obviously raise (P<0.001), show Golden Hamster hyperlipemia model modeling success.Successive administration is after 4 weeks, the level (P<0.001) that positive control drug Xuezhikang, asiatic acid are low, high dose group all obviously can reduce hyperlipi demic hamsters serum TC, TG, LDL-C and TC/HDL-C.Xuezhikang, asiatic acid low dose group all can elevating HDL-C level (P<0.05), asiatic acid high dose energy elevating HDL-C level, but compare with model group and do not have significant difference.
2.3 asiatic acids are on the impact of hyperlipi demic hamsters liver function index
Asiatic acid is shown in Fig. 3 to the experimental result that hyperlipi demic hamsters liver function index affects.Compared with blank group, model group Hamster serum AST, ALT level all obviously raises (P<0.001, P<0.001).Successive administration is after 4 weeks, and positive control drug Xuezhikang obviously can reduce hyperlipi demic hamsters serum AST, ALT level (P<0.001, P<0.001).Asiatic acid low dose group, asiatic acid high dose group all obviously can reduce hyperlipi demic hamsters serum AST levels (P<0.001, P<0.001), Serum ALT levels (P<0.01, P<0.001) can be reduced simultaneously.
2.4 asiatic acid is on the impact of TC, TG, GSH-PX and SOD in hyperlipi demic hamsters hepatic tissue
The experimental result of asiatic acid on TC, TG, GSH-PX and SOD impact in hyperlipi demic hamsters hepatic tissue is shown in Fig. 4.Compared with blank group, in model group Golden Hamster hepatic tissue, TC, TG all obviously raise (P<0.001), SOD, GSH-PX level obviously reduces (P<0.001, P<0.05).Successive administration is after 4 weeks, positive control drug Xuezhikang obviously can reduce liver TC, TG level (P<0.001), obvious rising hepatic SOD (P<0.001), and liver GSH-PX level (P<0.01).Asiatic acid low dosage, asiatic acid high dose group all obviously can reduce hyperlipi demic hamsters hepatic tissue TC, TG level (P<0.001), increased SOD vigor (P<0.001) and GSH-PX level (P<0.001).
2.5 histological observation
Perusal Normal group Golden Hamster liver is bronzing, bright, clear-cut margin.Model control group liver is canescence, tarnish, edge become obtuse, and volume obviously increases; Xuezhikang group hepatic tissue color is that light red colour cast is yellow, and edge is sharp-pointed, and volume comparatively matched group increases; Asiatic acid respectively organizes that hepatic tissue color is slightly shallow compared with blank group color, and glossiness is slightly poor, and volume comparatively model group reduces.
Liver frozen section HE coloration result shows, substantially has no fat and drip in blank group lobules of liver structural integrity, hepatocyte; In model group hepatocyte, visible a large amount of fat drips, and hepatic cell fattydegeneration is serious; Xuezhikang group hepatocyte lactone drips comparatively model group obviously to be reduced; Asiatic acid is respectively organized Golden Hamster hepatocyte lactone and is dripped and to reduce to some extent compared with model group and to have minimizing trend, hepatic steatosis not obvious with dosage increase, and experimental result as shown in Figure 5.
In sum, the present invention is shown by lot of experiments result, and asiatic acid comprises acute and Diet hyperlipemia model to two kinds of hyperlipemia model and all has significant lipid-lowering effect; Meanwhile, the non-alcoholic fatty liver disease caused for hyperlipidemia model has and improves liver function, alleviates the effect of hepatic pathology infringement.Evident in efficacy with the antihyperglycemic hepatoprotective agent that it is prepared, be a kind of novel antihyperglycemic hepatoprotective agent that can be used for long-term lipid-lowering therapy.
Claims (8)
1. the purposes in prevention and therapy hyperlipidemia and fatty liver medicament prepared by an asiatic acid.
2. purposes as claimed in claim 1, it is characterized in that, described asiatic acid is as the medicine of sole active ingredient for the preparation of prevention and therapy hyperlipemia, and the medicine of prevention and therapy fatty liver.
3. a medicine for prevention and therapy hyperlipemia, containing the sole active ingredient of asiatic acid as this medicine.
4. the medicine of prevention and therapy hyperlipemia as claimed in claim 3, is characterized in that, also comprise pharmaceutically acceptable carrier in the medicine of described prevention and therapy hyperlipemia.
5. the medicine of prevention and therapy hyperlipemia as claimed in claim 3, it is characterized in that, the dosage form of the medicine of described prevention and therapy hyperlipemia is selected from tablet, pill, capsule, granule or oral liquid.
6. a medicine for prevention and therapy non-alcoholic fatty liver disease, containing the sole active ingredient of asiatic acid as this medicine.
7. the medicine of prevention and therapy non-alcoholic fatty liver disease as claimed in claim 6, is characterized in that, also comprise pharmaceutically acceptable carrier in described medicine.
8. the medicine of prevention and therapy non-alcoholic fatty liver disease as claimed in claim 6, it is characterized in that, the dosage form of described prevention and therapy non-alcoholic fatty liver disease medicine is selected from tablet, pill, capsule, granule or oral liquid.
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Cited By (4)
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| CN106306956A (en) * | 2016-08-24 | 2017-01-11 | 开平市水口镇卡摩商行 | Health-care drink |
| CN107056874A (en) * | 2016-12-28 | 2017-08-18 | 福建广生堂药业股份有限公司 | A kind of compound of asiatic acid tenofovir dipivoxil and preparation method thereof |
| CN108743596A (en) * | 2018-05-16 | 2018-11-06 | 厦门大学 | The pharmaceutical composition of disease and its application caused by a kind for the treatment of or prevention hyperlipidemia |
| CN111450102A (en) * | 2019-12-05 | 2020-07-28 | 广西医科大学 | Application of medicine for promoting lipid metabolism of non-alcoholic fatty liver cells |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106306956A (en) * | 2016-08-24 | 2017-01-11 | 开平市水口镇卡摩商行 | Health-care drink |
| CN107056874A (en) * | 2016-12-28 | 2017-08-18 | 福建广生堂药业股份有限公司 | A kind of compound of asiatic acid tenofovir dipivoxil and preparation method thereof |
| CN108743596A (en) * | 2018-05-16 | 2018-11-06 | 厦门大学 | The pharmaceutical composition of disease and its application caused by a kind for the treatment of or prevention hyperlipidemia |
| CN111450102A (en) * | 2019-12-05 | 2020-07-28 | 广西医科大学 | Application of medicine for promoting lipid metabolism of non-alcoholic fatty liver cells |
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