CN114588216A - Pharmaceutical composition with blood fat reducing effect and preparation method and application thereof - Google Patents

Pharmaceutical composition with blood fat reducing effect and preparation method and application thereof Download PDF

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Publication number
CN114588216A
CN114588216A CN202110518560.6A CN202110518560A CN114588216A CN 114588216 A CN114588216 A CN 114588216A CN 202110518560 A CN202110518560 A CN 202110518560A CN 114588216 A CN114588216 A CN 114588216A
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China
Prior art keywords
vitamin
grape
composition
seed extract
arginine
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Granted
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CN202110518560.6A
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Chinese (zh)
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CN114588216B (en
Inventor
靳洪涛
胡广
张培成
蒋建东
张金兰
庞菲
张萍
李阳阳
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Jilin Maifu Nutrition Technology Co ltd
Institute of Materia Medica of CAMS
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Jilin Maifu Nutrition Technology Co ltd
Institute of Materia Medica of CAMS
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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants

Abstract

The invention relates to a pharmaceutical composition with the efficacy of reducing blood fat, a preparation method and application thereof, wherein the composition contains 1-25% (w/w) of grape powder, 0.5-15% (w/w) of grape seed extract, 0.5-10% (w/w) of arginine, 0.5-10% (w/w) of vitamin C or vitamin E and a pharmaceutically acceptable carrier. The invention scientifically screens the grape powder, the grape seed extract, the L-arginine, the vitamin C or the vitamin E and the mixture ratio thereof of the pharmaceutical composition, and has the advantages of quick and lasting effect and excellent anti-oxidation and blood fat reduction effects.

Description

Pharmaceutical composition with blood fat reducing effect and preparation method and application thereof
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to a pharmaceutical composition with a blood fat reducing effect, and a preparation method and application thereof.
Background
The latest statistical results of the Ministry of health show that about 30 percent of patients with cardiovascular and cerebrovascular diseases in China are under 60 years old, the incidence rate is up to 13.6 percent, and the incidence rate of cardiovascular and cerebrovascular diseases of the old over 65 years old is up to 95 percent. Hyperlipidemia is an important risk factor for promoting hypertension, impaired glucose tolerance, diabetes, and may lead to fatty liver, liver cirrhosis, cholelithiasis, pancreatitis, fundus hemorrhage, blindness, peripheral vascular disease, claudication, hyperuricemia, etc. The research has proved that the grape seed extract has the functions of oxidation resistance, anti-inflammation, anti-tumor, and cardiovascular protection. But the blood fat reducing effect and the effect taking efficiency of the existing product need to be improved.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition with the efficacy of reducing blood fat, which contains 1-25% (w/w) of grape powder, 0.5-15% (w/w) of grape seed extract, 0.5-10% (w/w) of arginine, 0.5-10% (w/w) of vitamin C or vitamin E and a pharmaceutically acceptable carrier.
In a preferred embodiment of the present invention, the content of the grape powder in the composition is 5-20% (w/w), preferably 10-15% (w/w).
In the preferable technical scheme of the invention, the content of resveratrol in the grape powder is 1-10% (w/w), preferably 5-8% (w/w).
In a preferred embodiment of the present invention, the content of the grape seed extract in the composition is 1-10% (w/w), preferably 2-5% (w/w).
In the preferable technical scheme of the invention, the content of the proanthocyanidins in the grape seed extract is 90-100% (w/w), and preferably 95-98% (w/w).
In a preferred technical scheme of the invention, the procyanidin is oligomeric procyanidin.
In a preferred embodiment of the present invention, the average degree of polymerization of the oligomeric procyanidin is 2 to 6, preferably 3 to 4.
In a preferred embodiment of the present invention, the arginine content of the composition is 1-5% (w/w), preferably 2-4% (w/w).
In the preferable technical scheme of the invention, the arginine is L-arginine.
In a preferred embodiment of the present invention, the vitamin C or vitamin E content of the composition is 1-5% (w/w), preferably 2-4% (w/w).
In a preferred technical scheme of the invention, the pharmaceutically acceptable carrier is selected from any one of a filling agent and a flavoring agent or a combination thereof.
In a preferred embodiment of the present invention, the content of the filler in the composition is 55-90% (w/w), preferably 60-85% (w/w), preferably 65-83%, more preferably 70-80% (w/w).
In a preferred technical scheme of the invention, the filler is selected from any one of maltodextrin, starch, lactose, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, corn starch, cellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate, sorbitol and glycine or a combination thereof.
In a preferred embodiment of the present invention, the content of the flavoring agent in the composition is 0.5-5% (w/w), preferably 0.8-4% (w/w), more preferably 1-2% (w/w).
In a preferred technical scheme of the invention, the flavoring agent is selected from any one of sucralose, grape essence, erythritol, grape essence, xylitol, honey, sucrose, glucose, mogroside, malic acid, fumaric acid, citric acid, phosphoric acid, ethyl maltol, sodium citrate, sodium malate, acetic acid, sodium acetate, sodium hydrogen phosphate, sodium dihydrogen phosphate, carbonic acid, sodium carbonate, sulfonic acid, sodium sulfonate, glutamic acid, tartaric acid, sodium tartrate, lactic acid, sodium lactate, fumaric acid, sodium fumarate, itaconic acid, ascorbic acid, sodium ascorbate, nicotinic acid, sodium nicotinate, fumaric acid, alpha-ketoglutaric acid, fruit acid, sodium fruit acid, acetic acid, oxalic acid, succinic acid, carbon dioxide, citric acid and sodium citrate or a combination thereof.
In a preferred technical scheme of the invention, the composition contains 1-25% (w/w) of grape powder, 0.5-15% (w/w) of grape seed extract, 0.5-10% (w/w) of L-arginine, 0.5-10% (w/w) of vitamin C or vitamin E, 55-90% (w/w) of maltodextrin and 0.5-5% (w/w) of flavoring agent, wherein the flavoring agent is selected from any one or combination of citric acid, ethyl maltol, grape essence and sucralose.
In a preferred technical scheme of the invention, the composition contains 5-20% (w/w) of grape powder, 1-10% (w/w) of grape seed extract, 1-5% (w/w) of L-arginine, 1-5% (w/w) of vitamin C or vitamin E, 65-85% (w/w) of maltodextrin and 0.8-4% (w/w) of flavoring agent, wherein the flavoring agent is selected from any one or combination of citric acid, ethyl maltol, grape essence and sucralose.
In a preferred technical scheme of the invention, the composition contains 10-20% (w/w) of grape powder, 1-10% (w/w) of grape seed extract, 1-5% (w/w) of L-arginine, 1-5% (w/w) of vitamin C or vitamin E, 65-85% (w/w) of maltodextrin and 1-3% (w/w) of flavoring agent, wherein the flavoring agent is selected from any one or combination of citric acid, ethyl maltol, grape essence and sucralose.
In a preferred technical scheme of the invention, 10-15% (w/w) of grape powder, 2-5% (w/w) of grape seed extract, 2-4% (w/w) of L-arginine, 2-4% (w/w) of vitamin C or vitamin E and a flavoring agent with the content of maltodextrin of 70-80% (w/w) and 1-2% (w/w) are contained in the composition, wherein the flavoring agent is selected from any one or combination of citric acid, ethyl maltol, grape essence and sucralose.
In a preferred technical scheme of the invention, 10-20% (w/w) of grape powder, 2-5% (w/w) of grape seed extract, 2-4% (w/w) of L-arginine, 2-4% (w/w) of vitamin C or vitamin E and a flavoring agent with the content of maltodextrin of 70-80% (w/w) and 1-2% (w/w) are contained in the composition, wherein the flavoring agent is selected from any one or combination of citric acid, ethyl maltol, grape essence and sucralose.
In a preferred technical scheme of the invention, the preparation form of the composition is selected from any one of powder, tablets, capsules, granules, pills, powder, dripping pills, mixture, distillate, effervescent agents, paste, emulsion and tea.
The invention also aims to provide a preparation method of the pharmaceutical composition with the effect of reducing blood fat, which comprises the steps of weighing the required amount of grape powder, grape seed extract, arginine, vitamin C or vitamin E and pharmaceutically acceptable carriers, and uniformly mixing to obtain the pharmaceutical composition.
In a preferred technical scheme of the invention, the content of the grape powder in the composition is 1-25% (w/w), the content of the grape seed extract is 0.5-15% (w/w), the content of arginine is 0.5-10% (w/w), the content of vitamin C or vitamin E is 0.5-10% (w/w) and a pharmaceutically acceptable carrier.
In a preferred embodiment of the present invention, the content of the grape powder in the composition is 5-20%, preferably 10-15% (w/w).
In the preferable technical scheme of the invention, the content of resveratrol in the grape powder is 1-10% (w/w), preferably 5-8% (w/w).
In a preferred embodiment of the present invention, the content of the grape seed extract in the composition is 1-10% (w/w), preferably 2-5% (w/w).
In the preferable technical scheme of the invention, the content of the proanthocyanidins in the grape seed extract is 90-100% (w/w), and preferably 95-98% (w/w).
In a preferred technical scheme of the invention, the procyanidin is oligomeric procyanidin.
In a preferred embodiment of the present invention, the average degree of polymerization of the oligomeric procyanidin is 2 to 6, preferably 3 to 4.
In a preferred embodiment of the present invention, the arginine content of the composition is 1-5%, preferably 2-4% (w/w).
In a preferred technical scheme of the invention, the arginine is L-arginine.
In a preferred embodiment of the present invention, the vitamin C or vitamin E content of the composition is 1-5%, preferably 2-4% (w/w).
In a preferred embodiment of the present invention, the pharmaceutically acceptable carrier is selected from any one of a filler, a flavoring agent, and a lubricant, or a combination thereof.
In a preferred embodiment of the present invention, the content of the filler in the composition is 55-90% (w/w), preferably 65-85% (w/w), more preferably 70-80% (w/w).
In a preferred technical scheme of the invention, the filler is selected from any one of maltodextrin, starch, lactose, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, corn starch, cellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate, sorbitol and glycine or a combination thereof.
In a preferred embodiment of the present invention, the content of the flavoring agent in the composition is 0.5-5% (w/w), preferably 0.8-4% (w/w), more preferably 1-2% (w/w).
In a preferred technical scheme of the invention, the flavoring agent is selected from one or a combination of sucralose, grape essence, erythritol, xylitol, honey, sucrose, glucose, mogroside, malic acid, fumaric acid, citric acid, phosphoric acid, ethyl maltol, sodium citrate, sodium malate, acetic acid, sodium acetate, sodium hydrogen phosphate, sodium dihydrogen phosphate, carbonic acid, sodium carbonate, sulfonic acid, sodium sulfonate, glutamic acid, tartaric acid, sodium tartrate, lactic acid, sodium lactate, fumaric acid, sodium fumarate, itaconic acid, ascorbic acid, sodium ascorbate, nicotinic acid, sodium nicotinate, fumaric acid, alpha-ketoglutaric acid, fruit acid, sodium fruit acid, acetic acid, oxalic acid, succinic acid, carbon dioxide, citric acid and sodium citrate.
In a preferred technical scheme of the invention, the content of grape powder in the composition is 1-25% (w/w), the content of grape seed extract is 0.5-15% (w/w), the content of maltodextrin is 55-90% (w/w), the content of L-arginine is 0.5-10% (w/w), the content of vitamin C or vitamin E is 0.5-10%, and the content of flavoring agent is 0.5-5% (w/w), wherein the flavoring agent is selected from any one or combination of citric acid, ethyl maltol, grape essence and sucralose.
In a preferred technical scheme of the invention, the content of the grape powder in the composition is 5-20% (w/w), the content of the grape seed extract is 1-10% (w/w), the content of the maltodextrin is 65-85% (w/w), the content of the L-arginine is 1-5% (w/w), the content of the vitamin C or the vitamin E is 1-5%, and the content of the flavoring agent is 0.8-4% (w/w), wherein the flavoring agent is selected from any one of citric acid, grape essence, ethyl maltol and sucralose or a combination thereof.
In a preferred technical scheme of the invention, the content of the grape powder in the composition is 10-15% (w/w), the content of the grape seed extract is 2-5% (w/w), the content of maltodextrin is 70-80% (w/w), the content of L-arginine is 2-4% (w/w), the content of vitamin C or vitamin E is 2-4%, and the content of a flavoring agent is 1-2% (w/w), wherein the flavoring agent is selected from any one of citric acid, ethyl maltol, grape essence and sucralose or a combination thereof.
In the preferred technical scheme of the invention, the grape powder and the grape seed extract used in the invention are prepared by adopting a conventional extraction method in the field.
Another object of the present invention is to provide a pharmaceutical composition, wherein the content of proanthocyanidin in the composition is 1-10% (w/w), the content of resveratrol is 0.1-1% (w/w), and a pharmaceutically acceptable carrier.
In the preferable technical scheme, the average polymerization degree of the procyanidine is 3-4, and the monomer content is 10-15%.
In a preferred embodiment of the present invention, the pharmaceutically acceptable carrier is selected from any one of or a combination of fillers, antioxidants, flavors, and lubricants.
In a preferred embodiment of the present invention, the content of the filler in the composition is 55-90% (w/w), preferably, maltodextrin, starch, lactose, powdered sugar or derivatives thereof, cellulose or derivatives thereof, inorganic calcium salt, sorbitol or glycine or combinations thereof, preferably, the inorganic calcium salt is selected from any one or combinations of calcium sulfate, calcium phosphate, calcium hydrogen phosphate and precipitated calcium carbonate, more preferably, the cellulose derivative is selected from any one or combinations of microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose and hydroxypropyl methyl cellulose, preferably, the starch derivative is selected from any one or combinations of sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch and corn starch.
In a preferred embodiment of the present invention, the content of the filler in the composition is 65-85% (w/w), preferably 70-80% (w/w).
In a preferred embodiment of the present invention, the antioxidant in the composition is 0.5-10% (w/w), preferably any one or a combination of arginine, vitamin C, vitamin E, tert-butylhydroquinone, butylhydroxyanisole, and dibutylhydroxytoluene, and more preferably vitamin C or L-arginine.
In a preferred embodiment of the present invention, the antioxidant is present in the composition in an amount of 1-8% (w/w), preferably 3-5% (w/w).
In a preferred technical scheme of the invention, the content of the flavoring agent in the composition is 0.5-5% (w/w), and the flavoring agent is preferably any one or combination of sucralose, erythritol, xylitol, mogroside, citric acid, ethyl maltol, sucralose, essence and spice.
In a preferred technical scheme of the invention, the content of the flavoring agent in the composition is 0.8-4% (w/w), and preferably 1-2% (w/w).
In a preferred embodiment of the present invention, the content of the lubricant in the composition is 0.5-5% (w/w), and is preferably any one or a combination of aerosil, magnesium stearate, talc, aluminum hydroxide, boric acid, hydrogenated vegetable oil, and polyethylene glycol.
In a preferred embodiment of the present invention, the content of the lubricant in the composition is 1-4% (w/w), preferably 2-3% (w/w).
In the preferable technical scheme of the invention, the content of the proanthocyanidins in the composition is 1-10% (w/w), the content of the resveratrol is 0.1-1% (w/w), the content of the arginine is 1-5% (w/w), and the content of the vitamin C or the vitamin E is 1-5% (w/w).
In the preferable technical scheme of the invention, the content of proanthocyanidins in the composition is 3%, the content of resveratrol is 0.68%, the content of arginine is 2%, and the content of vitamin C or vitamin E is 2%.
The invention aims to provide a preparation method of a pharmaceutical composition, which comprises the following steps: weighing required amount of procyanidine, resveratrol and pharmaceutically acceptable carrier, and mixing.
In a preferred embodiment of the present invention, the pharmaceutically acceptable carrier is selected from any one of or a combination of fillers, antioxidants, flavors, and lubricants.
The invention also aims to provide application of the pharmaceutical composition in preparing a preparation for reducing blood fat.
In a preferred embodiment of the present invention, the amount of the composition of the present invention is 5 g/time, 1 to 3 times/day, preferably 1 to 2 times, depending on the age, sex, health condition, current treatment status, drug combination, etc. of the patient.
Unless otherwise indicated, when the present invention relates to percentages between liquids, said percentages are volume/volume percentages; the invention relates to the percentage between liquid and solid, said percentage being volume/weight percentage; the invention relates to the percentages between solid and liquid, said percentages being weight/volume percentages; the balance being weight/weight percent.
Compared with the prior art, the beneficial technical effects of the invention comprise:
1. the invention scientifically screens the grape powder, the grape seed extract, the L-arginine and the vitamin C (vitamin E) of the pharmaceutical composition and the proportion thereof, and has the advantages of quick, lasting and excellent anti-oxidation and blood fat reduction effects.
2. The preparation method of the composition has the advantages of simple and convenient operation, suitability for industrial production and the like.
Detailed Description
The present invention is described below with reference to examples. The invention is not limited to the examples.
The grape powder and the grape seed extract used in the specific embodiment are all commercially available, wherein the resveratrol content in the grape powder is 5%, and the proanthocyanidin content in the grape seed extract is 95%.
EXAMPLE 1 preparation of a composition according to the invention
Weighing 20g of grape powder, 5g of grape seed extract, 5g of L-arginine, 5g of vitamin C and 65g of maltodextrin, and uniformly mixing to obtain the grape seed extract.
Example 2 preparation of a composition according to the invention
Weighing 15g of grape powder, 10g of grape seed extract, 5g of L-arginine, 5g of vitamin C and 65g of maltodextrin, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 3 preparation of the composition of the invention
Weighing 20g of grape powder, 10g of grape seed extract, 2g of L-arginine, 3g of vitamin C and 65g of corn starch, and uniformly mixing to obtain the grape powder.
EXAMPLE 4 preparation of the composition of the invention
Weighing 10g of grape powder, 5g of grape seed extract, 5g of L-arginine, 5g of vitamin C and 75g of corn starch, and uniformly mixing to obtain the grape powder.
EXAMPLE 5 preparation of the composition of the invention
Weighing 15g of grape powder, 1g of grape seed extract, 5g of L-arginine, 4g of vitamin E and 75g of maltodextrin, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 6 preparation of a composition according to the invention
Weighing 10g of grape powder, 10g of grape seed extract, 2g of L-arginine, 3g of vitamin E and 75g of maltodextrin, and uniformly mixing to obtain the grape seed extract.
Example 7 preparation of a composition according to the invention
Weighing 5g of grape powder, 10g of grape seed extract, 5g of L-arginine, 5g of vitamin C and 75g of resistant dextrin, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 8 preparation of a composition of the invention
Weighing 5g of grape powder, 5g of grape seed extract, 2g of L-arginine, 3g of vitamin C and 85g of resistant dextrin, and uniformly mixing to obtain the grape seed extract.
Example 9 preparation of a composition according to the invention
Weighing 10g of grape powder, 1g of grape seed extract, 2g of L-arginine, 2g of vitamin C and 85g of maltodextrin, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 10 preparation of the composition of the invention
Weighing 12g of grape powder, 10g of grape seed extract, 5g of L-arginine, 5g of vitamin C, 65g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 1g of sucralose, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 11 preparation of a composition according to the invention
Weighing 10g of grape powder, 10g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 75g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 1g of sucralose, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 12 preparation of a composition of the invention
Weighing 15g of grape powder, 5g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 75g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 1g of sucralose, and uniformly mixing to obtain the grape wine.
EXAMPLE 13 preparation of a composition of the invention
Weighing 10g of grape powder, 1g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 85g of maltodextrin, 1g of citric acid, 0.5g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape powder.
EXAMPLE 14 preparation of a composition of the invention
Weighing 10g of grape powder, 1g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 85g of maltodextrin, 1g of citric acid, 0.5g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape powder.
EXAMPLE 15 preparation of a composition of the invention
Weighing 14g of grape powder, 5g of grape seed extract, 2g of L-arginine, 2g of vitamin C and 77g of maltodextrin, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 16 preparation of a composition of the invention
Weighing 3g of proanthocyanidins, 1g of resveratrol, 2g of arginine, 2g of vitamin C and 92g of maltodextrin, and uniformly mixing to obtain the resveratrol-containing liposome.
EXAMPLE 17 preparation of a composition of the invention
Weighing 5g of proanthocyanidins, 5g of resveratrol, 5g of arginine, 5g of vitamin C and 80g of maltodextrin, and uniformly mixing to obtain the resveratrol.
EXAMPLE 18 preparation of a composition of the invention
Weighing 5g of proanthocyanidins, 5g of resveratrol, 5g of arginine, 5g of vitamin C and 80g of maltodextrin, and uniformly mixing to obtain the resveratrol.
EXAMPLE 19 preparation of a composition of the invention
Weighing 3g of proanthocyanidins, 1g of resveratrol, 5g of arginine, 5g of vitamin C and 86g of maltodextrin, and uniformly mixing to obtain the resveratrol-containing material.
EXAMPLE 20 preparation of the composition of the invention
Weighing 3g of proanthocyanidins, 0.68g of resveratrol, 2g of arginine, 2g of vitamin C, 90.5g of maltodextrin, 1g of citric acid, 0.32g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the traditional Chinese medicine.
EXAMPLE 21 preparation of a composition of the invention
Weighing 5g of proanthocyanidins, 1g of resveratrol, 5g of arginine, 5g of vitamin C, 81g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 1g of sucralose, and uniformly mixing to obtain the resveratrol-containing gel.
EXAMPLE 22 preparation of a composition of the invention
Weighing 1g of grape powder, 15g of grape seed extract, 10g of L-arginine, 10g of vitamin C10g, 60g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 2g of sucralose, and uniformly mixing to obtain the grape wine.
EXAMPLE 23 preparation of a composition of the invention
Weighing 25g of grape powder, 0.5g of grape seed extract, 0.5g of L-arginine, 0.5g of vitamin C, 70g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 1.5g of sucralose, and uniformly mixing to obtain the grape powder.
EXAMPLE 24 preparation of a composition of the invention
Weighing 15g of grape powder, 10g of grape seed extract, 3g of L-arginine, 3g of vitamin C, 65g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 2g of sucralose, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 25 preparation of a composition of the invention
Weighing 10g of grape powder, 10g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 75g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 1g of sucralose, and uniformly mixing to obtain the grape wine.
EXAMPLE 26 preparation of a composition of the invention
Weighing 10g of grape powder, 10g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 75g of maltodextrin, 0.5g of citric acid, 2g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape powder.
EXAMPLE 27 preparation of a composition of the invention
Weighing 14g of grape powder, 5g of grape seed extract, 2g of L-arginine, 2g of vitamin C, 75g of maltodextrin, 0.5g of citric acid, 1g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape powder.
EXAMPLE 28 preparation of a composition of the invention
Weighing 12g of grape powder, 8g of grape seed extract, 4g of L-arginine, 4g of vitamin C, 70g of maltodextrin, 0.5g of citric acid, 1g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape powder.
EXAMPLE 29 preparation of a composition of the invention
Weighing 15g of grape powder, 5g of grape seed extract, 2g of L-arginine, 2g of vitamin C, 74g of maltodextrin, 0.5g of citric acid, 1g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape powder.
EXAMPLE 30 preparation of a composition of the invention
Weighing 13g of grape powder, 6g of grape seed extract, 3g of L-arginine, 3g of vitamin C, 73.5g of maltodextrin, 0.5g of citric acid, 0.5g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape powder.
Test example 1Research on effect of composition of the invention on improving lipid metabolism of hyperlipidemic mice
1. Experimental Material
Male SPF grade C57BL/6J mice of 6 months of age, weighing 28.61 + -2.16 g, were reared in a single cage at room temperature 25 + -2 deg.C, 45% relative humidity, 12h/12h light-dark cycle, with free access to food and water during the rearing period.
1.2 Experimental drugs and reagents
Figure BDA0003062941960000161
Figure BDA0003062941960000171
1.3 Main Experimental Equipment
Figure BDA0003062941960000172
2. Experimental methods
2.1 grouping, modeling and administration of test animals
The test mice were fed with high-fat diet for molding. The high-fat diet was fed to 30 mice successfully molded during the test period, and the mice were divided into three groups of 10 mice each, and the mice were gavaged daily for six weeks with a gavage amount of 0.2ml/g mouse body weight. The control group was gavage with water, and the test group was gavage with the aqueous solution of the composition of example 27, wherein the gavage dose of test group 1 was 1.0g/kg of mouse body weight, and the gavage dose of test group 2 was 3.0g/kg of mouse body weight.
After the last administration, the test mice were fasted for 12 hours, anesthetized, blood was taken from the eyeballs, centrifuged at 3500rpm/min for 10min, and then serum was separated. White adipose tissues of subcutaneous inguinal and brown adipose tissues at scapular regions of the mice were separated, weighed, and fixed in 4% tissue cell fixing solution.
2.2 glucose tolerance assay
After the test mice are continuously gavaged for six weeks, fasting is carried out for 12h, blood is taken by a tail shearing method, the test mice are injected with glucose in an abdominal cavity according to a dose of 2g/kg, and the blood glucose value of the test mice is measured by glucose test paper at 0min before injection and 30min, 60min, 90min and 120min after injection.
2.3 determination of the ratio of adipose tissue weight to body weight
Accurately weighing subcutaneous inguinal white fat and scapular brown fat of the mouse, and calculating the ratio of inguinal white fat weight (iWAT) to body weight and scapular brown fat weight (BAT) to body weight.
2.4 detection of blood lipid-related indicators
The serum Total Cholesterol (TC), Triglyceride (TG), Low-Density Lipoprotein Cholesterol (LDL-C) content was determined according to the kit instructions.
The test data were statistically processed using SAS 8.2 software, and the mean value. + -. standard deviation (of the mean value: (A))
Figure BDA0003062941960000182
Figure BDA0003062941960000183
) Representing experimental data, and adopting a one-factor analysis of variance method for normal data and multi-group comparison(ANOVA)，P<A difference of 0.05 is statistically significant.
3. Results of the experiment
3.1 Effect of the compositions of the present invention on mouse body weight (see Table 1)
The composition of example 27 of the present invention was administered to mice for six weeks after continuous gavage, and the body weight of the mice in the test group was not significantly affected as compared to the control group.
TABLE 1
Figure BDA0003062941960000181
Note: compared with the control group, the compound of the formula,**P<0.01
3.2 Effect of the compositions of the invention on blood lipid levels in mice
Mice were tested by continuous gavage for six weeks with the composition of example 27 of the present invention, which significantly reduced TG, TC and LDL-C levels (P <0.05 or P <0.01) in high-fat mice compared to the control group. The results are shown in Table 2.
TABLE 2
Figure BDA0003062941960000191
Note: compared with the aged group,*P<0.05，**P<0.01
3.3 Effect of the compositions of the present invention on the specific gravity of subcutaneous fat in mice
Both Brown Adipose Tissue (BAT) and White Adipose Tissue (WAT) of mammals play an important role in the homeostasis of energy metabolism balance in the body, but the anatomical structures, morphologies and functions of both tissues are quite different. WAT is a major energy storage organ that accumulates excess energy in the body in the form of Triglycerides (TG), and its abnormal differentiation is associated with obesity formation and metabolic disorders. BAT is a thermogenic tissue that promotes energy metabolism and consumption by accelerating the oxidative thermogenesis of fat.
Mice were tested by continuous gavage for six weeks with the composition of example 27 of the present invention, which significantly reduced the subcutaneous fat specific weight (P <0.01) in high-fat mice compared to the control group. The results are shown in Table 3.
TABLE 3
Figure BDA0003062941960000192
Note: compared with the control group, the compound of the formula,**P<0.01
3.4 study of the Effect of the composition of the present invention on glucose tolerance in mice
Continuous gavage test mice have the composition of the example 27 for six weeks, and compared with a control group, the composition can remarkably improve the sugar tolerance (P <0.01) of high-fat mice. The results are shown in Table 4.
TABLE 4
Figure BDA0003062941960000201
Note: compared with the control group, the compound of the formula,**P<0.01
the above description of the specific embodiments of the present invention is not intended to limit the present invention, and those skilled in the art may make various changes and modifications according to the present invention without departing from the spirit of the present invention, which is defined in the appended claims.

Claims (10)

1. A pharmaceutical composition with blood fat reducing effect is characterized in that the composition contains 1-25% (w/w) of grape powder, 0.5-15% (w/w) of grape seed extract, 0.5-10% (w/w) of arginine, 0.5-10% (w/w) of vitamin C or vitamin E and a pharmaceutically acceptable carrier.
2. The composition according to claim 1, wherein the grape powder is present in an amount of 5-20%, preferably 10-15% (w/w) and the resveratrol is present in an amount of 1-10% (w/w), preferably 5-8% (w/w).
3. The composition according to any one of claims 1 to 2, wherein the content of the grape seed extract in the composition is 1-10% (w/w), preferably 2-5% (w/w).
4. A composition according to any one of claims 1 to 3, wherein the proanthocyanidin content in the grape seed extract is from 90% to 100% (w/w), preferably from 95% to 98% (w/w).
5. The composition according to any one of claims 1 to 4, wherein arginine is present in the composition in an amount of 1 to 5%, preferably 2 to 4% (w/w), and wherein the vitamin C or vitamin E is present in an amount of 1 to 5%, preferably 2 to 4% (w/w).
6. The composition according to any one of claims 1 to 5, wherein the composition comprises 1 to 25% (w/w) of grape powder, 0.5 to 15% (w/w) of grape seed extract, 0.5 to 10% (w/w) of L-arginine, 0.5 to 10% (w/w) of vitamin C or vitamin E, 55 to 90% (w/w) of maltodextrin, 0.5 to 5% (w/w) of a flavoring agent, wherein the flavoring agent is any one or combination of citric acid, ethyl maltol, grape essence and sucralose.
7. A process for the preparation of a pharmaceutical composition according to any one of claims 1 to 6, comprising in particular the steps of: uniformly mixing the required amount of grape powder, grape seed extract, arginine, vitamin C or vitamin E and pharmaceutically acceptable carrier to obtain the grape seed extract.
8. A pharmaceutical composition is characterized in that the content of proanthocyanidin in the composition is 1-10% (w/w), the content of resveratrol is 0.1-1% (w/w), and a pharmaceutically acceptable carrier.
9. The method for preparing a composition according to claim 8, comprising the steps of: weighing required amount of procyanidine, resveratrol and pharmaceutically acceptable carrier, and mixing.
10. Use of a pharmaceutical composition according to any one of claims 1-6 or claim 8 for the preparation of a preparation having hypolipidemic effect.
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