CN111905029A - A kind of medicinal combination containing gentisic acid and application thereof - Google Patents

Abstract

The invention belongs to the field of health care products, in particular to a gentisic acid-containing medicinal composition and application thereof. The active ingredients of the composition are gentisic acid and Cabernet Sauvignon grape skin pomace extract, wherein: the mass percentage of the active ingredients is 0.3-1.2wt%, and the rest are pharmaceutically acceptable carriers; the active ingredients , the mass percentage ratio of gentisic acid to Cabernet Sauvignon grape skin pomace extract is 1:5. The application of the medicinal composition containing gentisic acid and Cabernet Sauvignon grape skin pomace extract is for treating obesity and related diseases. The medicinal composition obtained by the invention, the active ingredients of gentisic acid and Cabernet Sauvignon grape skin pomace extract can effectively inhibit the body obesity caused by the high-fat and high-sugar diet, improve the body's glucose tolerance and insulin resistance, and thus prevent obesity. It opens up new avenues for the treatment of schizophrenia and related diseases.

Description

A kind of medicinal combination containing gentisic acid and application thereof

technical field

The invention relates to the field of natural polyphenols, in particular to a medicinal composition containing gentisic acid and Cabernet Sauvignon grape skin pomace extract and its application in health food.

Background technique

For nearly half a century, obesity has become a prevalent chronic disease worldwide. Currently, 1.9 billion adults are overweight in the world, and 609 million adults are obese. Overweight and obese people account for 39% of the total population, and it is expected that the prevalence of obesity and overweight will continue to rise in the next two to three decades. Both remain major public health burdens worldwide. Epidemiological studies have shown that overweight and obesity are important risk factors for diabetes, hypertension, cardiovascular disease, cancer, and premature death. Therefore, preventing and treating overweight and obesity and related complications have become a public health priority.

The root cause of obesity is that the body's energy intake is greater than energy expenditure, and excess energy is stored in white fat in the form of triglycerides, leading to obesity. Although the factors affecting obesity and overweight are complex, the underlying cause is that energy intake is greater than energy expenditure, so the two strategies for preventing and treating obesity are reducing energy intake and increasing energy expenditure. However, the ways of restricting energy are often accompanied by different degrees of side effects or difficult for patients to adhere to, such as gastric bypass surgery, gastrectomy and dieting, etc. Therefore, seeking foods that increase the body's energy expenditure has become a new strategy for preventing and treating obesity.

Gentianic acid, 2,5-dihydroxy benzoic acid (DHB), is a polyhydroxy phenolic acid widely found in Chinese herbal medicines and berries. There are few studies on the function of gentisic acid in resistance to obesity, and mainly focus on the effect of gentisic acid-rich plant extracts on obesity resistance, and there is no report on the study of gentisic acid monomer. Cabernet Sauvignon grape skin pomace extract (Grape extract, GE) is an important by-product in the brewing process of Cabernet Sauvignon. It is not only used as food coloring agent, but also has antioxidant, cancer prevention, anti-dementia, anti-cardiovascular Diseases and other biological activities are used in health food. The full use of grape pomace is beneficial to increase its added value and reduce the potential burden on the environment.

In the prior art, the effects of compounding gentisic acid and Cabernet Sauvignon grape skin pomace extract to promote body heat production, resist obesity and improve insulin resistance have not yet been reported.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a medicinal composition containing gentisic acid and its application, which can be used for compounding gentisic acid and Cabernet Sauvignon grape skin pomace extract for the treatment of obesity and related diseases. Open up new therapeutic avenues for the treatment of obesity and related diseases.

In order to achieve the above object, the present invention provides the following technical solutions:

A medicinal composition containing gentisic acid, the active ingredients of the composition are gentisic acid and grape skin polyphenol extract, wherein:

The mass percentage of the active ingredient is 0.3wt%-1.2wt%, and the rest are pharmaceutically acceptable carriers.

In the active ingredient, the mass percentage ratio of gentisic acid and Cabernet Sauvignon grape skin pomace extract is 1:5.

The carrier is a liposome drug carrier or a nano drug carrier.

The mass percentage of the active ingredient is 0.3wt%-1.2wt%; the mass percentage ratio of gentisic acid to Cabernet Sauvignon grape skin pomace extract is 1:5.

The medicine can effectively inhibit body obesity induced by high-fat and high-sugar diet, and the inhibition rate is 13.76%-18.88%.

The medicine reduces the subcutaneous fat rate of the body by 29.79%-39.59%, the epididymal fat rate of the body by 33.73%-34.33%, and the liver weight percentage by 29.49%-33.33%.

The medicine increases the insulin sensitivity of the body, reduces the glucose tolerance level of the body by 5.37%-13.36%, and reduces the insulin resistance level by 15.63%-25.86%.

The composition increases the oxygen consumption level of the body by 6.45%-11.66%.

The dosage of the pharmaceutical composition is 28-112 mg/kg body weight/day.

Application of a medicinal composition containing gentisic acid for treating obesity and related diseases.

The associated disease is insulin resistance.

Compared with the prior art, the beneficial effects of the present invention are:

1) The present invention can be used in medicines for the treatment of obesity and related diseases;

2) the medicine for the treatment of obesity and related diseases of the present invention, its active ingredient can effectively suppress the body obesity caused by high-fat and high-sugar diet to gentisic acid and grape skin polyphenol extract;

3) the medicine for the treatment of obesity and related diseases of the present invention, its active ingredient gentisic acid and Cabernet Sauvignon grape skin pomace extract can improve the glucose tolerance and insulin resistance of the body, thus for the treatment of obesity and related diseases. Treatment opens up new avenues of treatment.

Description of drawings

Hereinafter, the embodiments of the present invention will be described in detail in conjunction with the accompanying drawings, wherein, five treatment groups are divided into low-fat control group, high-fat control group, low-concentration compound of gentisic acid and Cabernet Sauvignon grape skin pomace extract. Matching group (0.5mg/ml gentisic acid + 2.5mg/ml Cabernet Sauvignon grape skin pomace extract), medium concentration compound group (1mg/ml gentisic acid + 5mg/ml Cabernet Sauvignon grape skin pomace extract) and high concentration compound group (2mg/ml gentisic acid+10mg/ml Cabernet Sauvignon grape skin pomace extract), in which gentisic acid and Cabernet Sauvignon grape skin pomace extract were dissolved in drinking water; different lowercase letters indicate significant differences (P<0.05) (n=8-10):

Figure 1 shows the effect of gentisic acid and Cabernet Sauvignon grape pomace extract on the body weight of mice;

Figure 2 shows the effects of gentisic acid and Cabernet Sauvignon grape pomace extract on the weight of various organs in mice;

Figure 3 shows the effects of gentisic acid and Cabernet Sauvignon grape pomace extract on glucose tolerance and area under the curve in mice;

Figure 4 shows the effects of gentisic acid and Cabernet Sauvignon grape pomace extract on insulin resistance and area under the curve in mice;

Figure 5 shows the effects of gentisic acid and Cabernet Sauvignon grape pomace extract on thermogenic capacity and energy expenditure in mice.

Detailed ways

The present invention will be further described below in conjunction with specific embodiments.

The application of gentisic acid and Cabernet Sauvignon grape skin pomace extract in medicine for treating obesity and related diseases can improve the glucose tolerance and insulin resistance of the body.

A medicine for treating obesity and related diseases, the active ingredients of the medicine are gentisic acid and Cabernet Sauvignon grape skin pomace extract, and the mass percentage of the active ingredients is 0.3wt%-1.2wt% (3mg/mL -12mg/mL); wherein, the ratio of the mass percent of gentisic acid to Cabernet Sauvignon grape pomace extract is 1:5.

Preferably, the Cabernet Sauvignon grape skin pomace extract in the medicine is a powder obtained by ethanol extraction, macroporous resin chromatography and freeze-drying technology of grape skin pomace. Among them, total sugar contains 16.1mg/g, total protein 13.1mg/g, oil 9.88mg/g, moisture 43.31mg/g, and total phenol 604.11mg/g.

Preferably, the mass percentage of the active ingredient of the medicine is 0.3wt%-1.2wt%.

Preferably, the drug can effectively inhibit the body obesity induced by high-fat and high-sugar diet, and the inhibition rates of low-, medium- and high-concentration compound treatments are 13.76%, 18.88%, and 18.85%, respectively.

Preferably, the medicine can significantly reduce the weight of subcutaneous fat, epididymal fat and liver, and the weight of subcutaneous fat is reduced by 29.79%, 37.96% and 39.59% respectively after low, medium and high concentration compound treatment; the weight of epididymal fat is reduced respectively 37.14%, 40.01% and 40.81%; liver weight decreased by 28.16%, 31.42% and 31.83%, respectively.

Preferably, the pharmaceutically acceptable carriers are liposomal drug carriers and nanodrug carriers.

Preferably, the drug increases insulin sensitivity in mice by 5.28%-13.36% in glucose tolerance levels and 15.34%-25.85% in insulin resistance. 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 energy expenditure level of mice by 6.45%-11.66%.

Example 1 Inhibition verification test of high-fat and high-sugar diet-induced obesity

Unless otherwise specified, the C57BL/6J mice used in the following examples were purchased from Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd.; the gentisic acid and glucose used were chromatographically pure and purchased from Sigma-Aldrich (Shanghai) Trading Co., Ltd. Company; the Cabernet Sauvignon grape skin pomace extract used is derived from the powder of Cabernet Sauvignon grape skin pomace after ethanol extraction, macroporous resin chromatography and freeze-drying, which contains 16.1mg/g total sugar and 13.1mg/g total protein. g, oil 9.88mg/g, moisture 43.31mg/g, total phenol 604.11mg/g; the insulin used was biosynthetic human insulin and was commercially obtained from regular channels.

In order to verify the effect of gentisic acid and Cabernet Sauvignon grape skin pomace extract against obesity, the present invention adopts high-fat and high-sugar food to feed C57BL/6J mice. The 4-week-old mice were randomly divided into five experimental groups according to body weight, with 12 mice in each group. The three experimental groups are:

In the low-fat control group, the food energy of this group was 3.2kcal/g, containing 4.5% fat, and the drinking water was purified water.

In the high-fat control group, the food energy of this group was 4.7kcal/g, containing 25% fructose and 25% lard, and the drinking water was purified water.

A group fed with gentisic acid and Cabernet Sauvignon grape skin pomace extract in drinking water, wherein the food energy of this group is 4.7kcal/g, containing 25% fructose and 25% lard, and drinking the invention for treating obesity The medicine for the disease and related diseases, the active ingredients of the medicine are gentisic acid and Cabernet Sauvignon grape skin pomace extract, and the active ingredient concentration is 0.3wt%-1.2wt%; The mass ratio of the extracts was 1:5.

The mice in each of the above test groups were given free access to food and water during the feeding period. For 12 weeks of continuous administration, the average amount of food, water or drugs consumed was recorded every 3 days, and body weight was recorded once a week. After the experiment, blood was collected from the eyeball and the mice were sacrificed by cervical dislocation, and the liver, epididymal fat and subcutaneous fat were weighed.

The results are shown in Figure 1. The treatment of gentisic acid and Cabernet Sauvignon grape skin pomace can effectively inhibit the obesity of mice induced by high-fat and high-sugar diet. Specifically, mice treated with low, medium and high concentrations Body weight decreased by 13.76%, 18.88% and 18.85%, respectively.

Figure 2 shows that gentisic acid treatment with Cabernet Sauvignon grape pomace extract reduces major tissue weight in mice. The weight of subcutaneous fat decreased by 29.79%, 37.96% and 39.59% respectively; the weight of epididymal fat was decreased by 37.14%, 40.01% and 40.81%; the weight of liver decreased by 28.16% and 31.42% respectively after low, medium and high concentration compound treatment and 31.83%.

Example 2 Verification test of glucose tolerance and insulin resistance of the body induced by high-fat and high-sugar diet

Obesity is often accompanied by dysregulation of glucose homeostasis, resulting in glucose tolerance and insulin resistance. Therefore, the present invention has carried out the following experiments on the mice of each experimental group in the tenth week of administration in Example 1:

1. Intraperitoneal glucose tolerance test (intraperitoneal glucose tolerance test, IGTT): in Example 1, the mice after 11 weeks of administration were fasted for 16h, and the glucose of 1.5g/kg body weight was intraperitoneally injected after weighing, and the blood glucose meter was used to separate the test. Blood glucose levels were measured at 0 min, 15 min, 30 min, 60 min, 90 min and 120 min.

As shown in Figure 3-1 in Figure 3, with the prolongation of time after glucose injection, the blood sugar of the mice in the high-fat control group increased rapidly, while the compound treatment group of gentisic acid and Cabernet Sauvignon grape skin pomace slowed down the increase. a trend.

As shown in 3-2 in Figure 3, the glucose tolerance of mice in each test group changed after injection. Specifically, the glucose tolerance of mice in the compound treatment group of gentisic acid and Cabernet Sauvignon grape skin residue The area under the glucose tolerance curve of mice in the high-fat control group was significantly lower than that in the high-fat control group, and the low, medium and high concentration compound treatments decreased by 5.28%, 8.95% and 13.36%, respectively. This indicated that the treatment group of gentisic acid and Cabernet Sauvignon grape pomace extract significantly alleviated the glucose tolerance of mice caused by high-fat and high-sugar diet.

2. Insulin tolerance test (insulin tolerance test, ITT): the mice in each test group in Example 1 were fasted for 6 hours after administration for 12 weeks, and after weighing, the insulin of 1 IU/kg body weight was injected intraperitoneally. Blood glucose values were measured at 0min, 5min, 30min, 45min and 60min.

The results are shown in Figure 4. After the compound treatment of low, medium and high concentrations of gentisic acid and Cabernet Sauvignon grape skin pomace extract, the area under the insulin resistance curve of mice was higher than that of mice in the high-fat and high-glucose group. The area under the dose curve decreased by 15.34%, 17.47% and 25.85%, indicating that gentisic acid and grape skin polyphenol extract can significantly improve insulin sensitivity

In conclusion, the compound treatment of gentisic acid and Cabernet Sauvignon grape skin pomace extract can improve the insulin resistance of mice induced by high-fat and high-sugar diet.

Example 3 Body heat production test

The mice treated for the 10th week in Example 1 were placed in the environment of room temperature (25°C) and cold stimulation (4°C) for 3 hours, and the body temperature of the mice was measured; the Cooled Incubator/LabMaster (TSE Company) software was used to monitor the energy of the mice for 24 hours. spending level.

The results are shown in Figure 5-1 in Figure 5. The treatment group of the compound treatment group with gentisic acid and Cabernet Sauvignon grape skin pomace enhanced the body heat production of mice in a cold environment, and it can be seen from Figure 5-2 in Figure 5. , compared with the high-fat control mice, the treatment group treated with gentisic acid and Cabernet Sauvignon grape skin pomace increased the oxygen consumption levels of mice by 6.88%, 6.48% and 11.66%, indicating that gentian acid The treatment group of acid and Cabernet Sauvignon grape skin pomace extract enhanced the energy metabolism of mice, and then resisted obesity and insulin resistance and other related diseases.

Claims (10)

1. a medicinal composition containing gentisic acid, is characterized in that: the active ingredient of described composition is gentisic acid and Cabernet Sauvignon grape skin residue extract, wherein: The mass percentage of the active ingredient is 0.3wt% to 1.2wt%, and the rest are pharmaceutically acceptable carriers; In the active ingredient, the mass percentage ratio of gentisic acid and Cabernet Sauvignon grape skin pomace extract is 1:5. 2. the medicinal composition containing gentisic acid according to claim 1, is characterized in that: The carrier is a liposome drug carrier or a nano drug carrier. 3. the medicinal composition containing gentisic acid and Cabernet Sauvignon grape skin pomace extract according to claim 1, is characterized in that: The mass percentage of the active ingredient is 0.3wt%-1.2wt%; the mass percentage ratio of gentisic acid and grape skin extract is 1:5. 4 . The gentisic acid-containing pharmaceutical composition according to claim 1 , wherein the medicine can effectively inhibit obesity induced by high-fat and high-sugar diet, and the inhibition rate is 13.76%-18.85%. 5 . 5. The medicinal composition containing gentisic acid according to claim 1, wherein the medicine reduces the body subcutaneous fat rate by 29.79%-39.59%, and reduces the body epididymal fat rate by 33.73%-34.33% %, the liver weight percentage decreased by 29.49%-33.33%. 6. The medicinal composition containing gentisic acid according to claim 1, wherein the medicine increases the insulin sensitivity of the body, reduces the glucose tolerance level of the body by 5.37%-13.36%, and the insulin The tolerance level was reduced by 15.63%-25.86%. 7 . The gentisic acid-containing medicinal composition according to claim 1 , wherein the composition increases the energy expenditure of the body by 6.45%-11.66%. 8 . 8. The gentisic acid-containing pharmaceutical composition according to claim 1, wherein the dosage of the pharmaceutical composition is 28-112 mg/kg body weight/day. 9. The application of the gentisic acid-containing pharmaceutical composition as claimed in claim 1 in the preparation of a medicine for treating obesity and related diseases. 10. The use according to claim 9, wherein the related disease is insulin resistance.

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