CN111905029A - Medicinal composition containing gentisic acid and application thereof - Google Patents
Medicinal composition containing gentisic acid and application thereof Download PDFInfo
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- CN111905029A CN111905029A CN202010870963.2A CN202010870963A CN111905029A CN 111905029 A CN111905029 A CN 111905029A CN 202010870963 A CN202010870963 A CN 202010870963A CN 111905029 A CN111905029 A CN 111905029A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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Abstract
The invention belongs to the field of health care products, and particularly relates to a pharmaceutical composition containing gentisic acid and application thereof. The effective components of the composition are gentisic acid and cabernet sauvignon skin residue extracts, wherein: the mass percentage of the effective components is 0.3-1.2 wt%, and the balance is pharmaceutically acceptable carriers; in the effective components, the mass percentage ratio of the gentisic acid to the cabernet sauvignon skin residue extract is 1: 5. The application of the medicinal composition containing gentisic acid and cabernet sauvignon skin residue extract is used for treating obesity and related diseases. The medicinal composition obtained by the invention has the effective components of gentisic acid and cabernet sauvignon grape skin residue extract, can effectively inhibit the body obesity caused by high-fat and high-sugar diet, and improves the glucose tolerance and insulin resistance of the body, thereby opening up a new treatment way for treating obesity and related diseases.
Description
Technical Field
The invention relates to the field of natural polyphenols, in particular to a medicinal composition containing gentisic acid and cabernet sauvignon skin residue extract and application thereof in health-care food.
Background
Obesity has become a chronic disease prevalent worldwide for nearly half a century. Currently, 19 billion adults are overweight globally, 6.09 billion adults are obese, and the overweight and obese population account for 39% of the total population, and the prevalence of obesity and overweight is expected to continue to rise in the next two or three decades, both of which remain important public health burden epidemiological studies facing urgent needs throughout the world that show that overweight and obesity are important risk factors for diabetes, hypertension, cardiovascular disease, cancer, and premature death, and thus the prevention and treatment of overweight, obesity, and related complications has become a public health priority.
The fundamental reason for obesity is that the body's energy intake is greater than the energy expenditure, and the excess energy is stored in white fat in the form of triglycerides, resulting in obesity. Although the factors affecting obesity and overweight are complex, the underlying reason is that energy intake is greater than energy expenditure, so two strategies for preventing and treating obesity are to reduce energy intake and increase energy expenditure. However, the energy-limiting means is often accompanied by various degrees of side effects or difficult to persist to patients themselves, such as gastric bypass, gastrectomy, and diet, and thus the search for foods that increase the expenditure of body energy is a new strategy for preventing and treating obesity.
Gentisic acid, 2, 5-dihydroxybenzoic acid (DHB), is a polyhydroxyphenolic acid that is widely found in Chinese herbal medicines and berries. The existing functional research on gentisic acid for resisting obesity is less, and mainly focuses on the effect of a plant extract rich in gentisic acid on resisting obesity, and the research on gentisic acid monomers is not reported. The cabernet sauvignon skin residue extract (GE) is an important byproduct in the brewing process of cabernet sauvignon wine, is not only used as a food colorant, but also applied to health food due to the biological activity of resisting oxidation, preventing cancer, dementia, cardiovascular diseases and the like. The full utilization of the grape skin residues is beneficial to improving the added value of the grape skin residues and reducing the potential burden on the environment.
The effects of promoting body heat production, resisting obesity and improving insulin resistance by compounding gentisic acid and cabernet sauvignon grape skin residue extract in the prior art are not reported yet.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition containing gentisic acid and application thereof, wherein the gentisic acid and the cabernet sauvignon skin residue extract are compounded for treating obesity and related diseases, and the application can open up a new treatment way for treating the obesity and the related diseases.
In order to achieve the purpose, the invention provides the following technical scheme:
a pharmaceutical composition containing gentisic acid, the effective components of the composition are gentisic acid and grape skin polyphenol extract, wherein:
the mass percentage of the effective components is 0.3 wt% -1.2 wt%, and the balance is pharmaceutically acceptable carriers.
In the effective components, the mass percentage ratio of the gentisic acid to the cabernet sauvignon skin residue extract is 1: 5.
The carrier is a liposome drug carrier or a nano drug carrier.
The mass percentage of the effective components is 0.3-1.2 wt%; the mass percentage ratio of the gentisic acid to the cabernet sauvignon skin residue extract is 1: 5.
The medicine can effectively inhibit the body obesity induced by high-fat high-sugar diet, and the inhibition rate is 13.76% -18.88%.
The medicine can reduce the subcutaneous fat rate of an organism by 29.79-39.59%, reduce the epididymis fat rate of the organism by 33.73-34.33%, and reduce the weight percentage of the liver by 29.49-33.33%.
The medicine increases insulin sensitivity of the body, and reduces the glucose tolerance level of the body by 5.37-13.36% and the insulin tolerance level by 15.63-25.86%.
The composition increases the level of oxygen consumption by the body by 6.45% to 11.66%.
The dosage of the medicinal composition is 28-112 mg/kg body weight/day.
Use of a pharmaceutical composition comprising gentisic acid for the treatment of obesity and related disorders.
The related disease is insulin resistance.
Compared with the prior art, the invention has the beneficial effects that:
1) the invention can be used in the medicine for treating obesity and related diseases;
2) the effective components of the medicine for treating obesity and related diseases can effectively inhibit the body obesity caused by high-fat and high-sugar diet for the gentisic acid and grape skin polyphenol extract;
3) the effective components of the medicine for treating obesity and related diseases, namely the gentisic acid and the cabernet sauvignon skin residue extract, can improve the glucose tolerance and the insulin resistance of an organism, so that a new treatment way is opened up for the treatment of obesity and related diseases.
Drawings
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings, in which five treatment groups are divided into a low-fat control group, a high-fat control group, a low-concentration combination group of gentisic acid and cabernet sauvignon skin residue extract (0.5mg/ml gentisic acid +2.5mg/ml cabernet sauvignon skin residue extract), a medium-concentration combination group (1mg/ml gentisic acid +5mg/ml cabernet sauvignon skin residue extract) and a high-concentration combination group (2mg/ml gentisic acid +10mg/ml cabernet sauvignon skin residue extract), in which gentisic acid and cabernet sauvignon skin residue extract are dissolved in drinking water; different lower case letters indicate significant differences (P <0.05) (n ═ 8-10):
figure 1 shows the effect of gentisic acid and cabernet sauvignon skin pomace extract on mouse body weight;
FIG. 2 shows the effect of gentisic acid and Vitis vinifera peel residue extract on the weight of each organ of mice;
FIG. 3 shows the effect of gentisic acid and Vitis vinifera peel residue extract on glucose tolerance and area under the curve in mice;
FIG. 4 shows the effect of gentisic acid and Vitis vinifera peel residue extract on insulin resistance and area under the curve in mice;
figure 5 shows the effect of gentisic acid and cabernet sauvignon skin pomace extract on the thermogenic capacity and energy expenditure of mice.
Detailed Description
The invention is further described with reference to specific examples.
An application of gentisic acid and cabernet sauvignon skin residue extract in medicine for treating obesity and related diseases can improve glucose tolerance and insulin resistance of organism.
A medicament for treating obesity and related diseases, the effective components of the medicament are gentisic acid and cabernet sauvignon skin residue extract, the mass percentage of the effective components is 0.3 wt% -1.2 wt% (3mg/mL-12 mg/mL); wherein the mass percentage ratio of the gentisic acid to the cabernet sauvignon skin residue extract is 1: 5.
Preferably, the extract of the cabernet sauvignon grape skin residue in the medicine is powder prepared by ethanol extraction, macroporous resin chromatography and freeze drying of the grape skin residue. Wherein the total sugar content is 16.1mg/g, total protein content is 13.1mg/g, oil content is 9.88mg/g, water content is 43.31mg/g, and total phenol content is 604.11 mg/g.
Preferably, the mass percentage of the active ingredients of the medicine is 0.3 wt% -1.2 wt%.
Preferably, the medicament can effectively inhibit high-fat and high-sugar diet-induced body obesity, and the inhibition rates of the low, medium and high concentration compound treatment are respectively 13.76%, 18.88% and 18.85%.
Preferably, the medicine can remarkably reduce the weight of subcutaneous fat, epididymal fat and liver, and the weight of the subcutaneous fat is respectively reduced by 29.79%, 37.96% and 39.59% after low, medium and high concentration compound treatment; the weight of epididymis fat is reduced by 37.14 percent, 40.01 percent and 40.81 percent respectively; liver weight was reduced by 28.16%, 31.42% and 31.83%, respectively.
Preferably, the pharmaceutically acceptable carriers are liposomal drug carriers and nano-drug carriers.
Preferably, the drug increases insulin sensitivity in mice with a 5.28% -13.36% increase in glucose tolerance and a 15.34% -25.85% increase in insulin tolerance. The glucose tolerance level is the area under the glucose tolerance curve, and the insulin tolerance level is the area under the insulin tolerance curve.
Preferably, the drug increases the level of energy expenditure in mice by 6.45% to 11.66%.
Example 1 test for inhibition of high fat and high sugar diet induced body obesity
Unless otherwise indicated, the C57BL/6J mice used in the following examples were purchased from Experimental animals technology, Inc., Viton, Beijing; gentisic acid and glucose used were chromatographically pure and purchased from sigma aldrich trade ltd; the extract of the skin residue of Cabernet Sauvignon is derived from powder of the skin residue of Cabernet Sauvignon after ethanol extraction, macroporous resin chromatography and freeze drying, wherein the total sugar content is 16.1mg/g, the total protein content is 13.1mg/g, the oil content is 9.88mg/g, the water content is 43.31mg/g, and the total phenol content is 604.11 mg/g; the insulin used is a biosynthetic human insulin commercially available from regular sources.
In order to verify the effect of gentisic acid and cabernet sauvignon grape skin residue extract on resisting obesity, the C57BL/6J mouse is fed by high-fat high-sugar grains. 4-week-old mice were randomly divided by body weight into five test groups of 12 mice each. The three test groups were:
a low fat control group wherein the diet fed the group had an energy of 3.2kcal/g, 4.5% fat and the drinking water was purified water.
And (3) a high-fat control group, wherein the group is fed with 4.7kcal/g of food, 25% of fructose and 25% of lard, and drinking water is purified water.
The food fed by the group has energy of 4.7kcal/g, contains 25% of fructose and 25% of lard oil, and the medicine for treating obesity and related diseases is drunk, wherein the effective components of the medicine are the gentisic acid and the cabernet sauvignon skin residue extract, and the concentration of the effective components is 0.3-1.2 wt%; wherein the mass part ratio of the gentisic acid to the cabernet sauvignon skin residue extract is 1: 5.
Mice in each of the above test groups were allowed free access to food and water during feeding. The administration was continued for 12 weeks, and the average amount of food, water or drug consumed was recorded every 3 days, and the body weight was recorded every week. After the experiment was completed, the eyeball was bled and the cervical vertebrae were dislocated to sacrifice the mouse, and the liver, epididymal fat and subcutaneous fat were weighed.
The results are shown in fig. 1, and the treatment of gentisic acid and the extract of the skin residue of the grapes with cabernet sauvignon can effectively inhibit the obesity induced by high-fat and high-sugar diets of the mice, and specifically, the weight of the mice is reduced by 13.76%, 18.88% and 18.85% after the low, medium and high concentration compound treatment respectively.
Figure 2 shows that gentisic acid and cabernet sauvignon skin residue extract treatment reduced the major tissue weight of mice. The weight of subcutaneous fat after low, medium and high concentration compound treatment is respectively reduced by 29.79 percent, 37.96 percent and 39.59 percent; the weight of epididymis fat is reduced by 37.14 percent, 40.01 percent and 40.81 percent respectively; liver weight was reduced by 28.16%, 31.42% and 31.83%, respectively.
Example 2 high fat high sugar diet induced body glucose tolerance and insulin resistance validation test
Obesity is often accompanied by a dysregulation of glucose metabolic homeostasis, resulting in glucose tolerance and insulin resistance. Thus, the present invention performed the following tests on mice of each test group at 10 weeks of administration in example 1:
1. intraperitoneal Glucose Tolerance Test (IGTT): mice administered 11 weeks in example 1 were fasted for 16 hours, weighed, and subjected to intraperitoneal injection of 1.5g/kg body weight of glucose, and blood glucose values were measured with a glucometer at 0min, 15min, 30min, 60min, 90min, and 120min, respectively.
As shown in fig. 3-1, the blood glucose levels of mice in the high-fat control group rapidly increased with time after glucose injection, and the combination of gentisic acid and the extract of the skin residue of cabernet sauvignon slowed down this trend.
As shown in 3-2 of fig. 3, the glucose tolerance of the mice in each test group was changed after injection, specifically, the area under the glucose tolerance curve of the mice in the combination treatment group of gentisic acid and cabernet sauvignon skin residue extract was significantly lower than that of the mice in the high-fat control group, and the low, medium and high concentration combination treatments were reduced by 5.28%, 8.95% and 13.36%, respectively. This indicates that the combination treatment of gentisic acid and cabernet sauvignon grape skin residue extract significantly eases the glucose tolerance of mice caused by high fat and high sugar diet.
2. Insulin Tolerance Test (ITT): mice in each test group of example 1 after administration for 12 weeks were fasted for 6 hours, weighed, and subjected to intraperitoneal injection of 1IU/kg body weight of insulin, and blood glucose values were measured with a glucometer for 0min, 5min, 30min, 45min and 60min, respectively.
The results are shown in fig. 4, after the combination treatment of the low, medium and high concentration medicines gentisic acid and the cabernet sauvignon grape skin residue extract, the areas under the mouse insulin resistance curve are reduced by 15.34%, 17.47% and 25.85% compared with the areas under the mouse insulin resistance curve of the high fat and high sugar group, which shows that the gentisic acid and the grape skin polyphenol extract can obviously improve the insulin sensitivity
In conclusion, the combination treatment of gentisic acid and cabernet sauvignon grape skin residue extract can improve the high-fat high-sugar diet induced insulin resistance of mice.
Example 3 in vivo thermogenesis test
The mice treated at the 10 th week in example 1 were placed in a room temperature (25 ℃) and cold stimulation (4 ℃) environment for 3 hours, respectively, and the body temperature of the mice was measured; the energy expenditure levels of the 24h mice were monitored using the Cooled Incubator/LabMaster (TSE Corp.) software.
The results are shown in 5-1 in fig. 5, the treatment of the combination treatment group of gentisic acid and cabernet sauvignon grape skin residue extract enhances the body heat production of mice in cold environment, and as can be seen from 5-2 in fig. 5, compared with the mice of the high-fat control group, the treatment of the combination treatment group of gentisic acid and cabernet sauvignon grape skin residue extract enhances the oxygen consumption level of the mice by 6.88%, 6.48% and 11.66%, which shows that the treatment of the combination treatment group of gentisic acid and cabernet sauvignon grape skin residue extract enhances the energy metabolism of the mice, thereby resisting obesity, insulin resistance and other related diseases.
Claims (10)
1. A pharmaceutical composition comprising gentisic acid, characterized in that: the effective components of the composition are gentisic acid and cabernet sauvignon skin residue extracts, wherein:
the mass percentage of the effective components is 0.3-1.2 wt%, and the balance is pharmaceutically acceptable carriers;
in the effective components, the mass percentage ratio of the gentisic acid to the cabernet sauvignon skin residue extract is 1: 5.
2. The pharmaceutical composition comprising gentisic acid according to claim 1, characterized in that:
the carrier is a liposome drug carrier or a nano drug carrier.
3. The pharmaceutical composition of claim 1 comprising gentisic acid and cabernet sauvignon peel residue extract, wherein:
the mass percentage of the effective components is 0.3-1.2 wt%; the mass percentage ratio of the gentisic acid to the grape skin extract is 1: 5.
4. The pharmaceutical composition comprising gentisic acid according to claim 1, characterized in that: the medicine can effectively inhibit the body obesity induced by high-fat high-sugar diet, and the inhibition rate is 13.76% -18.85%.
5. The pharmaceutical composition comprising gentisic acid according to claim 1, characterized in that: the medicine can reduce the subcutaneous fat rate of an organism by 29.79-39.59%, reduce the epididymis fat rate of the organism by 33.73-34.33%, and reduce the weight percentage of the liver by 29.49-33.33%.
6. The pharmaceutical composition comprising gentisic acid according to claim 1, characterized in that: the medicine increases insulin sensitivity of the body, and reduces the glucose tolerance level of the body by 5.37-13.36% and the insulin tolerance level by 15.63-25.86%.
7. The pharmaceutical composition comprising gentisic acid according to claim 1, characterized in that: the composition increases body energy expenditure by 6.45-11.66%.
8. The pharmaceutical composition comprising gentisic acid according to claim 1, characterized in that: the dosage of the medicinal composition is 28-112 mg/kg body weight/day.
9. Use of a pharmaceutical composition comprising gentisic acid as claimed in claim 1 in the manufacture of a medicament for the treatment of obesity and related diseases.
10. Use according to claim 9, characterized in that: the related disease is insulin resistance.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002322623A1 (en) * | 2002-07-24 | 2004-02-09 | Ohio University | Methods and compositions for treating diabetes mellitis |
| ES2315119A1 (en) * | 2006-08-16 | 2009-03-16 | Action Medicines, S.L. | Use of derivatives 2.5 -dihidrocibencenicos in the manufacture of medicines and cosmetics (Machine-translation by Google Translate, not legally binding) |
| KR20110031722A (en) * | 2009-09-21 | 2011-03-29 | 주식회사 푸드웰 | A method for preparing grape skin extracts |
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2020
- 2020-08-26 CN CN202010870963.2A patent/CN111905029A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002322623A1 (en) * | 2002-07-24 | 2004-02-09 | Ohio University | Methods and compositions for treating diabetes mellitis |
| ES2315119A1 (en) * | 2006-08-16 | 2009-03-16 | Action Medicines, S.L. | Use of derivatives 2.5 -dihidrocibencenicos in the manufacture of medicines and cosmetics (Machine-translation by Google Translate, not legally binding) |
| KR20110031722A (en) * | 2009-09-21 | 2011-03-29 | 주식회사 푸드웰 | A method for preparing grape skin extracts |
Non-Patent Citations (1)
| Title |
|---|
| 张艳华等: "葡萄籽原花青素对高脂高糖饮食诱导代谢综合征大鼠干预作用", 《食品科学》 * |
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Application publication date: 20201110 |