CN111529709A

CN111529709A - Composition for weight control and reversing atherosclerosis

Info

Publication number: CN111529709A
Application number: CN202010520698.5A
Authority: CN
Inventors: 汤鲁宏; 汤宁
Original assignee: Beijing Yisiteng Translation Service Co ltd
Current assignee: Beijing Yisiteng Translation Service Co ltd
Priority date: 2020-06-03
Filing date: 2020-06-03
Publication date: 2020-08-14

Abstract

The present invention belongs to the field of food recipe technology for specific medical use. In particular to a composition which can be used for weight control and can reverse atherosclerosis. It provides a specific medical formula food which can reverse atherosclerosis and has good effects of losing weight, reducing blood fat and controlling postprandial blood sugar. The invention not only greatly improves the bioavailability of the oral L-ascorbic acid fatty acid ester by inhibiting the intestinal pancreatic lipase and enables the oral L-ascorbic acid fatty acid ester to play a role in reversing atherosclerosis, but also achieves the health-care effect of controlling body weight by preventing the digestive absorption of fat, simultaneously achieves the health-care effects of controlling postprandial blood sugar and more effectively controlling body weight by preventing the digestive absorption of starch, has no toxic and harmful risks, and has wide application prospect in the public health field of controlling body weight and preventing cardiovascular and cerebrovascular diseases.

Description

Composition for weight control and reversing atherosclerosis

Technical Field

The present invention belongs to the field of food recipe technology for specific medical use. In particular to a composition which can be used for controlling body weight and reversing atherosclerosis.

Background

Cardiovascular and cerebrovascular diseases are the general names of cardiovascular and cerebrovascular diseases, and generally refer to ischemic or hemorrhagic diseases of heart, brain and systemic tissues caused by hyperlipidemia, blood viscosity, atherosclerosis, hypertension and the like. The cardiovascular and cerebrovascular diseases are common diseases seriously threatening the health of human beings, particularly the middle-aged and old people over 50 years old, have the characteristics of high morbidity, high disability rate and high mortality, even if the most advanced and perfect treatment means at present are applied, more than 50 percent of cerebrovascular accident survivors can not completely take care of the life, the number of people dying from the cardiovascular and cerebrovascular diseases in each year in the world reaches 1500 thousands, and the people live at the first of various causes of death.

The incidence of cardiovascular and cerebrovascular diseases in China is also in a growing trend, and the mortality rate is high. In 14 hundred million people in China, the number of patients with cardiovascular and cerebrovascular diseases reaches 2.83 million, wherein 1300 million stroke, 1100 million coronary heart disease, 500 million pulmonary heart disease, 450 million heart failure, 250 million rheumatic heart disease, 200 million congenital heart disease and 2.45 million hypertension are included. Cardiovascular and cerebrovascular diseases become the leading cause of death of residents in China, the death rate is higher than that of tumors and other diseases, the death rate accounts for more than 40 percent of the death rate of resident diseases, and the cardiovascular and cerebrovascular diseases seriously harm physical and mental health of people and harmonious development of society. The total hospitalization cost of cardiovascular and cerebrovascular diseases is rapidly increased, and the annual speed increase is much higher than the national production total value increase in 2004 to the present. The burden of cardiovascular and cerebrovascular diseases in China is gradually increased, which becomes a great public health problem and the prevention and treatment of the cardiovascular and cerebrovascular diseases are not easy.

A large number of researches prove that the occurrence and development of cardiovascular and cerebrovascular diseases are all related to lipid oxidation in vivo, lipid substances retained by blood vessel walls are oxidized, most of low-density lipoproteins (oxLDL) in blood are oxidized and modified lipoproteins, and the oxidized low-density lipoproteins (oxLDL) are involved in the formation of atherosclerosis and finally cause the attack of cardiovascular and cerebrovascular diseases such as cerebral infarction, myocardial infarction and the like.

As a fat-soluble form of vitamin C, L-ascorbyl palmitate has many properties that vitamin C does not have, can easily pass through cell membranes and erythrocytes, reaches tissues and organs that vitamin C itself cannot reach, is absorbed by cells and accumulated in cells, protects cells and erythrocytes of the body from oxidative damage, and repairs tissues that have suffered oxidative damage. The application of L-ascorbyl palmitate in resisting aging and preventing cardiovascular and cerebrovascular diseases is based on the development research of Dr. His study and subsequent clinical studies showed that L-ascorbyl palmitate, when used in combination with vitamin C, lysine and proline, was able to strengthen arterial vessel walls, relieve and reverse atherosclerosis.

Unfortunately, L-ascorbyl palmitate, an esterified derivative of vitamin C, has a low oral bioavailability of only about 10% due to its degradation to vitamin C and palmitic acid by pancreatic lipase in the digestive tract, resulting in a significant reduction in the clinical effects of alleviating and reversing atherosclerosis.

How to improve the oral bioavailability of L-ascorbyl palmitate still becomes the bottleneck for generating the actual clinical application effect. The research on the aspect is not reported at home and abroad.

Disclosure of Invention

The invention aims to provide a composition for weight control and capable of reversing atherosclerosis, so as to meet the requirements and desires of people for relieving and reversing atherosclerosis and reducing the risk of cardiovascular and cerebrovascular diseases. The invention provides a specific medical formula food which can reverse atherosclerosis and has good effects of losing weight, reducing blood fat and controlling postprandial blood sugar. The invention greatly improves the bioavailability of the oral L-ascorbic acid fatty acid ester by inhibiting intestinal pancreatic lipase, and exerts the effect of reversing atherosclerosis, simultaneously achieves the health-care effect of controlling body weight by preventing the digestive absorption of fat, simultaneously achieves the health-care effect of controlling postprandial blood sugar and more effectively controlling body weight by preventing the digestive absorption of starch, has no toxic and harmful risks, and has wide application prospect in the public health field of controlling body weight and preventing cardiovascular and cerebrovascular diseases.

The purpose of the invention can be realized by the following technical scheme:

a composition is prepared. The composition consists of the following components:

1) l-ascorbic acid fatty acid ester, the content is 300 to 600 mg/g;

2) intestinal digestive enzyme inhibitor in 200-500 mg/g;

3) l-ascorbic acid in an amount of 50 to 300 mg/g;

4) amino acid, the content is 50 to 100 mg/g; and

5) an acceptable base.

Wherein the ascorbic acid fatty acid ester can be L-ascorbyl palmitate, L-ascorbyl laurate, L-ascorbyl myristate, L-ascorbyl stearate, L-ascorbyl oleate, L-ascorbyl linoleate, L-ascorbyl linolenate, L-ascorbyl eicosapentaenoic acid ester, L-ascorbyl docosahexaenoate or one or more of the combination thereof. Wherein the intestinal digestive enzyme inhibitor is lipase inhibitor, amylase inhibitor or their combination, and can be epigallocatechin gallate (EGCG), or oolong tea extract, tea polyphenols, green tea extract, navy bean extract, peanut shell extract, grape seed extract, wheat bran extract, folium Nelumbinis extract, Curcuma rhizome extract, rhizoma Alpiniae Officinarum extract, semen Trigonellae extract, fructus Piperis Longi extract, ramulus Mori extract, cortex Mori extract, rhizoma Cyperi extract or radix Rhodiolae extract. The L-ascorbic acid can be L-ascorbic acid, or can be sodium L-ascorbate, calcium L-ascorbate, or one or more of them. The amino acid may be bromhydric acid, or lysine, histidine or their mixture. The matrix can be solid powder composed of sweetener, essence, pigment, anticaking agent, solid lubricant and carrier, or liquid composed of one or more of vegetable oil, animal oil, emulsifier and water.

The composition can be provided in the form of solid powder, or can be provided in the form of oily, pasty or slurry liquid, or can be prepared into the form of tablet, capsule or soft capsule. The composition can be orally taken to play the effects of controlling weight, reducing blood fat and reversing atherosclerosis, and has a better control effect on the increase of postprandial blood sugar.

Has the advantages that:

the invention discovers for the first time that the intestinal tract digestive enzyme inhibitor with lipase inhibition and the L-ascorbic acid fatty acid ester can greatly improve the oral bioavailability of the L-ascorbic acid fatty acid ester by oral administration simultaneously, ensure that the L-ascorbic acid fatty acid ester enters the body in an original shape, and exert the effects of relieving and reversing atherosclerosis after the L-ascorbic acid inhibitor, proline and lysine are used together. The invention also discovers that the L-ascorbic acid fatty acid ester, the L-ascorbic acid, the proline and the lysine in the composition can also play a stabilizing and synergistic role in an intestinal digestive enzyme inhibitor, so that the composition can better play an inhibiting role in lipase and amylase, has the effects of losing weight, reducing blood fat and controlling postprandial blood sugar, and can be used as a formula food with specific medical application for controlling body weight, controlling postprandial blood sugar, reducing blood fat and preventing cardiovascular and cerebrovascular diseases.

Detailed Description

The following examples will illustrate the method of operation of the present invention in detail, but should not be construed as limiting the invention thereto.

Example 1

60g of xylitol, 0.5g of orange essence, 0.1g of orange pigment, 10g of silicon dioxide, 10g of magnesium stearate and 19.4g of light calcium carbonate powder are uniformly mixed to form 100g of solid matrix.

600g of L-ascorbyl palmitate, 200g of lotus leaf extract, 50g of L-ascorbic acid, 50g of proline and 50g of lysine were added to 50g of the base, and the mixture was stirred while adding the L-ascorbyl palmitate, the lotus leaf extract and the lysine to uniformly mix the L-ascorbic acid, the proline and the lysine with the base. 1000g of the present composition was obtained in the form of powder.

Example 2

900g of soybean oil, 5g of sucrose ester, 15g of monoglyceride and 80g of water are mixed uniformly to form 1000g of a liquid matrix.

300g of L-ascorbic acid laurate, 200g of lotus leaf extract, 50g of L-ascorbic acid, 20g of proline, 15g of histidine and 15g of lysine were added to 400g of the base, and the mixture was stirred while adding the L-ascorbic acid laurate, the lotus leaf extract, the L-ascorbic acid, the proline, the histidine and the lysine to the base, so that the mixture and the base were uniformly mixed. Thus 1000g of the liquid composition was obtained.

Example 3

Taking lotus leaf extract raw powder and a proper amount of the composition prepared according to the example 1, putting the lotus leaf extract raw powder into potassium phosphate buffer solution containing 0.5 percent of sodium carboxymethylcellulose, ultrasonically dispersing and boiling the mixture to prepare 60mg/mL (calculated by lotus leaf extract) solution, and storing the solution at 4 ℃ for later use after cooling.

The lotus leaf extract solution and the composition solution prepared in example 1 were diluted with potassium phosphate buffer to give a diluted solution (25mg/L), 35. mu.L each of which was placed in a 96-well plate together with orlistat solution (25mg/L, positive control) and 35. mu.L of potassium phosphate buffer (blank), 15. mu.L of porcine pancreatic lipase solution (1g/L) prepared with potassium phosphate buffer was added, and after incubation at room temperature for 10min, 50. mu.L of 4-methylumbelliferyl oil ester (4-MUO) (0.1mmol/L) was added, and dynamic fluorescence measurement was performed at 37 ℃. The excitation wavelength and the absorption wavelength are 320 nm and 450nm respectively. The absorbance at 0 and 20min was measured. 3 replicates were taken and the assay repeated 3 times.

Inhibitory Activity of [1- (F)_s20-F_s0)/(F_b20-F_b0)]× 100% of total carbon atoms, wherein F_b0，F_b20The dynamic fluorescence absorption values of blank at 0 and 20min are respectively; f_s0，F_s20The dynamic fluorescence absorption values of the sample at 0 and 20min are respectively.

The determination result shows that the composition has very good stability and synergistic effect of the porcine pancreatic lipase inhibitor, and the inhibition rate of the porcine pancreatic lipase of the composition is 58% based on 100% of orlistat, compared with the inhibition rate of the lotus leaf extract which is only 38%.

Example 4

Taking lotus leaf extract raw powder and a proper amount of the composition prepared according to the example 1, putting the lotus leaf extract raw powder into potassium phosphate buffer (pH6.90) containing 0.5% sodium carboxymethylcellulose, ultrasonically dispersing and boiling the mixture to prepare 60mg/mL (calculated by lotus leaf extract) solution, and storing the solution at 4 ℃ for later use after cooling.

Adding 0.25mL of alpha-amylase solution and 0.25mL of one of the two solutions into 0.5mL of phosphate buffer solution (pH6.90), preheating at 37 ℃ for 10min, adding 0.5mL of 10g/L starch solution, accurately reacting for 5min, adding 1mL of 3, 5-dinitrosalicylic acid, placing in a boiling water bath for 10min, rapidly cooling in an ice water bath, adding 5mL of deionized water, and measuring the light absorption value at the wavelength of 540 nm. The blank was phosphate buffered saline instead of alpha-amylase solution, and the control was phosphate buffered saline instead of test solution. 1 α -AI Activity (1U) is defined as: the amount of alpha-AI required to inhibit the production of 1. mu. mol of glucose within 1 min. Relative alpha-AI activity (%) was defined as the percentage of alpha-AI activity after treatment of the white kidney bean extract compared to before treatment.

The test result shows that the composition has very good alpha-amylase inhibitor stability and synergistic effect, the alpha-amylase inhibition rate of the composition is 85%, and in contrast, the inhibition rate of the lotus leaf extract is only 58%.

Example 5

Taking L-ascorbyl palmitate raw powder and a proper amount of the composition prepared according to the example 1, putting the raw powder into distilled water containing 0.5% of sodium carboxymethylcellulose, performing ultrasonic dispersion, and preparing into 60mg/mL (calculated by L-ascorbyl palmitate) suspension for use.

Taking 12 healthy SD rats, randomly dividing into 2 groups, randomly dividing each group into 6 groups, fasting for 12h before experiment without water prohibition, respectively performing single intragastric administration on L-ascorbyl palmitate raw powder suspension and 1.5mL of the composition suspension, taking blood from retroorbital venous plexus of eyes at 0.25, 0.5, 1, 2, 4 and 6h before and after administration, taking about 0.5mL of blood each time, placing the blood into a heparinized 1.5mL centrifuge tube, centrifuging at 5000rpm for 10min, taking blood plasma, and storing at-20 ℃.

The content of L-ascorbyl palmitate in the plasma samples obtained was determined by HPLC using the following chromatographic conditions: a chromatographic column: symmetry C₁₈Column 4.6 × 250mm (i.d.5 μm), column temperature 30 deg.C, mobile phase methanol-water (65: 35), and flow rate 0.8 mL/min.

The test result shows that the composition has very good L-ascorbyl palmitate bioavailability improvement effect, and compared with L-ascorbyl palmitate raw powder suspension taken through intragastric administration, the bioavailability of the L-ascorbyl palmitate taken through intragastric administration can be improved from 10% to more than 50%.

Example 6

A series of powdered test compositions were prepared by preparing a solid base according to the formulation described in Table 1, and then adding L-ascorbic acid fatty acid ester, an intestinal digestive enzyme inhibitor, L-ascorbic acid and an amino acid to the solid base according to the formulation described in Table 2, following the procedure of example 1.

TABLE 1 formulation of the solid matrix

TABLE 2 formulation of the pulverulent compositions

Example 7

The lipase inhibition rate, amylase inhibition rate and bioavailability improvement effect of L-ascorbic acid fatty acid ester of the composition were examined according to the methods of examples 3 to 5, and the same results as those of the composition prepared in example 1 were obtained. The experimental result shows that the compounds also have good lipase inhibition rate, amylase inhibition rate and bioavailability improvement effect of the L-ascorbic acid fatty acid ester.

Example 8

A liquid base was prepared according to the formulation described in table 3, and then L-ascorbic acid fatty acid ester, intestinal digestive enzyme system inhibitor, L-ascorbic acid and amino acid were added to the base according to the formulation described in table 2, according to the method of example 2, to obtain a series of liquid test compositions.

TABLE 3 formulation of the liquid base

Example 9

Taking lotus leaf extract raw powder and a proper amount of the composition prepared according to the example 2, putting the lotus leaf extract raw powder into potassium phosphate buffer solution containing 0.5 percent of sodium carboxymethylcellulose, ultrasonically dispersing and boiling the mixture to prepare 60mg/mL (calculated by the lotus leaf extract) solution, and storing the solution at 4 ℃ for later use after cooling.

The lotus leaf extract solution and the composition solution prepared in example 2 were diluted with potassium phosphate buffer to give a diluted solution (25mg/L), 35. mu.L each of which was placed in a 96-well plate together with orlistat solution (25mg/L, positive control) and 35. mu.L of potassium phosphate buffer (blank), 15. mu.L of porcine pancreatic lipase solution (1g/L) prepared with potassium phosphate buffer was added, and after incubation at room temperature for 10min, 50. mu.L of 4-methylumbelliferyl oil ester (4-MUO) (0.1mmol/L) was added, and dynamic fluorescence measurement was performed at 37 ℃. The excitation wavelength and the absorption wavelength are 320 nm and 450nm respectively. The absorbance at 0 and 20min was measured. 3 replicates were taken and the assay repeated 3 times.

The determination result shows that the composition has very good stability and synergistic effect of the porcine pancreatic lipase inhibitor, and the inhibition rate of the porcine pancreatic lipase of the composition is 76% based on 100% of orlistat, compared with the inhibition rate of the lotus leaf extract which is only 38%.

Example 10

Taking lotus leaf extract raw powder and a proper amount of the composition prepared according to the example 2, putting the lotus leaf extract raw powder into potassium phosphate buffer (pH6.90) containing 0.5% sodium carboxymethylcellulose, ultrasonically dispersing and boiling the mixture to prepare 60mg/mL (calculated by lotus leaf extract) solution, and storing the solution at 4 ℃ for later use after cooling.

The test result shows that the composition has very good alpha-amylase inhibitor stability and synergistic effect, the alpha-amylase inhibition rate of the composition is 65%, and in contrast, the inhibition rate of the lotus leaf extract is only 58%.

Example 11

Taking L-ascorbyl palmitate raw powder and a proper amount of the composition prepared according to the example 2, putting the raw powder into distilled water containing 0.5% of sodium carboxymethylcellulose, performing ultrasonic dispersion, and preparing into 60mg/mL (calculated by L-ascorbyl palmitate) suspension for use.

Taking 12 healthy SD rats, randomly dividing into 2 groups, randomly dividing each group into 6 groups, fasting for 12h before experiment without water prohibition, respectively performing single intragastric administration on L-ascorbyl palmitate raw powder suspension and 1.5mL of the composition suspension, taking blood from retroorbital venous plexus of eyes at 0.25, 0.5, 1, 2, 4 and 6h before and after administration, taking about 0.5mL of blood each time, placing the blood into a heparinized 1.5mL centrifuge tube, centrifuging for 10min at 5000mpm, taking blood plasma, and storing at-20 ℃.

The content of L-ascorbyl palmitate in the plasma samples obtained was determined by HPLC using the following chromatographic conditions: a chromatographic column: symmetry C18 column 4.6X 250mm (i.d.5 μm); column temperature: 30 ℃; mobile phase: methanol-water (65: 35); the flow rate was 0.8 mL/min.

The test result shows that the composition has very good L-ascorbyl palmitate bioavailability improvement effect, and compared with L-ascorbyl palmitate raw powder suspension taken through intragastric administration, the bioavailability of the L-ascorbyl palmitate taken through intragastric administration can be improved from 10% to more than 60%.

Example 12

The lipase inhibition rate, amylase inhibition rate and bioavailability improvement effect of L-ascorbic acid fatty acid ester of the composition were examined according to the methods of examples 9 to 11, and the same results as those of the composition prepared in example 2 were obtained. The experimental result shows that the compounds also have good lipase inhibition rate, amylase inhibition rate and bioavailability improvement effect of the L-ascorbic acid fatty acid ester.

Claims

1. A composition can be used for weight control and reversing atherosclerosis. The composition consists of the following components:

1) l-ascorbic acid fatty acid ester, the content is 300 to 600 mg/g;

2) intestinal digestive enzyme inhibitor in 200-500 mg/g;

3) l-ascorbic acid in an amount of 50 to 300 mg/g;

4) amino acid, the content is 50 to 100 mg/g; and

5) an acceptable base.

2. The composition according to claim 1, wherein the L-ascorbic acid fatty acid ester is L-ascorbyl palmitate, L-ascorbyl laurate, L-ascorbyl myristate, L-ascorbyl stearate, L-ascorbyl oleate, L-ascorbyl linoleate, L-ascorbyl linolenate, L-ascorbyl eicosapentaenoate, L-ascorbyl docosahexaenoate, or a combination thereof.

3. The composition of claim 1, wherein the inhibitor of gut digestive enzymes, specifically lipase inhibitor, amylase inhibitor or a combination thereof, is epigallocatechin gallate (EGCG), or is a combination of one or more of oolong tea extract, tea polyphenols, green tea extract, navy bean extract, peanut shell extract, grape seed extract, wheat bran extract, lotus leaf extract, turmeric extract, galangal extract, fenugreek extract, piper longum extract, mulberry twig extract, mulberry bark extract, cyperus rotundus extract or rhodiola rosea extract.

4. The composition for weight management and reversing atherosclerosis according to claim 1, wherein said L-ascorbic acid is L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, or a combination of one or more thereof.

5. The composition for weight management and reversing atherosclerosis according to claim 1, wherein the amino acid is proline, lysine, histidine, or a combination of one or more thereof.

6. The composition for weight control and reversible atherosclerosis according to claim 1, wherein the matrix is solid powder comprising sweetener, essence, pigment, anticaking agent, solid lubricant and carrier, or liquid comprising one or more of vegetable oil, animal oil, emulsifier and water.

7. The composition for weight management and reversible atherosclerosis of claim 1, wherein said composition is provided in the form of a solid powder, an oily, pasty, or pasty liquid, or in the form of a compressed tablet, capsule, or soft capsule.

8. The composition according to claim 1 or 7 for weight control and reversing atherosclerosis, wherein the composition according to claim 1 or 7 is orally administered to achieve the effects of weight control, blood lipid reduction and reversing atherosclerosis, and also has better control effect on postprandial blood glucose rise.