CN112451598A - Pharmaceutical composition with lung injury prevention and treatment effects and preparation method and application thereof - Google Patents

Pharmaceutical composition with lung injury prevention and treatment effects and preparation method and application thereof Download PDF

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CN112451598A
CN112451598A CN202011410183.6A CN202011410183A CN112451598A CN 112451598 A CN112451598 A CN 112451598A CN 202011410183 A CN202011410183 A CN 202011410183A CN 112451598 A CN112451598 A CN 112451598A
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content
grape
composition
seed extract
arginine
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靳洪涛
张培成
张金兰
蒋建东
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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Priority to CN202011410183.6A priority Critical patent/CN112451598A/en
Publication of CN112451598A publication Critical patent/CN112451598A/en
Priority to CN202110518560.6A priority patent/CN114588216B/en
Priority to PCT/CN2021/135483 priority patent/WO2022117088A1/en
Priority to CN202111466222.9A priority patent/CN114601883B/en
Priority to US18/039,976 priority patent/US20240000880A1/en
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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
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    • 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
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    • 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 or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [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

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Abstract

The invention relates to a pharmaceutical composition with the effect of preventing and treating lung injury, 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 and a pharmaceutically acceptable carrier. The composition has the effects of preventing and treating lung injury and oxidative injury, inhibiting pulmonary fibrosis, regulating lipid metabolism and the like.

Description

Pharmaceutical composition with lung injury prevention and treatment effects and preparation method and application thereof
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to a pharmaceutical composition with a lung injury prevention and treatment effect, and a preparation method and application thereof.
Background
The lung injury comprises lung tissue injury caused by chest trauma, lung inhalation of harmful substances, lung infection and other factors, and further damages the structural integrity and the lung function of the lung. Atmospheric pollutants are easily inhaled into deep lung to cause respiratory tract injury, induce or aggravate various diseases, and cause inflammation reaction, oxidative stress, immune dysfunction and the like of organisms. The lung injury is closely related to the oxidative injury of tissue cells, and the lung injury is prevented and treated by anti-inflammatory drugs, antioxidants and immune function regulating drugs which are commonly used clinically. The research has proved that the grape seed extract has the functions of oxidation resistance, anti-inflammation, anti-tumor, and cardiovascular protection. However, the effect of the existing product on preventing and treating lung injury needs to be improved, and the effect is slow.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition with the effect of preventing and treating lung injury, wherein 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 arginine is 0.5-10% (w/w), the content of vitamin C 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 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, 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), and 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 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 maltodextrin is 55-90% (w/w), the content of L-arginine is 0.5-10% (w/w), the content of vitamin C is 0.5-10%, and the content of a 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 grape powder in the composition is 10-20% (w/w), the content of grape seed extract is 1-10% (w/w), the content of maltodextrin is 65-85% (w/w), the content of L-arginine is 1-5% (w/w), the content of vitamin C is 1-5% and the content of flavoring agent is 1-3% (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 a preferred technical scheme of the invention, the content of grape powder in the composition is 12-15% (w/w), the content of 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 is 2-4% and the content of 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 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 preventing and treating lung injury, which is obtained by uniformly mixing required amounts of grape powder, grape seed extract, arginine, vitamin C and pharmaceutically acceptable carriers.
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 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 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 60-85% (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 1-4% (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 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 maltodextrin is 55-90% (w/w), the content of L-arginine is 0.5-10% (w/w), the content of vitamin C is 0.5-10%, and the content of a 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 10-20% (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 is 1-5%, and the content of the flavoring agent is 1-3% (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 grape powder in the composition is 12-15% (w/w), the content of 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 is 2-4% and the content of 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.
The invention also aims to provide application of the pharmaceutical composition in preparing a preparation for preventing and treating lung injury.
In a preferred embodiment of the present invention, the lung injury is selected from any one of acute lung injury, inhalation lung injury, lung injury caused by smoke, lung injury caused by PM2.5, oxidative injury, ischemic lung injury, and complications thereof.
The invention also aims to provide application of the pharmaceutical composition in preparing a product for preventing and treating injury caused by hypoxia.
In a preferred embodiment of the present invention, the dosage of the composition of the present invention is related to the age, sex, health status, current treatment status, drug combination and the like of the patient, and the recommended dosage is 5 g/time and 1-3 times/day.
The grape powder and the grape seed extract used in the invention are prepared by adopting an extraction method in the field.
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 pharmaceutical composition provided by the invention is prepared by scientifically screening the proportion of the grape powder, the grape seed extract, the L-arginine and the vitamin C, has an excellent antioxidant effect, is quick and lasting in antioxidant effect, and is beneficial to preventing and treating diseases such as lung injury and injury caused by hypoxia.
2. The pharmaceutical composition provided by the invention has the advantages that the antioxidant damage capacity of an organism is remarkably improved, for example, the SOD activity of liver tissues and the GSH content of liver tissues of the organism are remarkably improved, the MDA and protein carbonyl content in the liver of the organism are remarkably reduced, the pharmaceutical composition has excellent effects of preventing and treating lung injury and oxidative damage, inhibiting pulmonary fibrosis, regulating lipid metabolism and the like, the lung injury, the anoxic injury and adverse effects on the lung function are remarkably reduced, the pathological change of the lung tissues and the lung inflammatory reaction caused by PM2.5 are remarkably reduced, and the improvement effect on the respiratory function caused by PM2.5 is realized.
3. The preparation method of the composition is simple and convenient to operate and is suitable for industrial production.
Drawings
FIG. 1 comparison of body weight changes in mice from group to group;
FIG. 2 comparison of MDA values of mice in each group;
FIG. 3 comparison of SOD values of mice in each group;
FIG. 4 comparison of GSH values for groups of mice;
FIG. 5 the change in body weight of rats in each group;
FIG. 6 cell number of rats in each group;
FIG. 7 the inflammatory response of the body caused by the key mRNA and PM2.5 in the rats of each group.
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 65g of maltodextrin, 20g of grape powder, 5g of grape seed extract, 5g of L-arginine and 5g of vitamin C, and uniformly mixing to obtain the grape seed extract.
Example 2 preparation of a composition according to the invention
Weighing 65g of maltodextrin, 15g of grape powder, 10g of grape seed extract, 5g of L-arginine and 5g of vitamin C, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 3 preparation of the composition of the invention
Weighing 65g of corn starch, 20g of grape powder, 10g of grape seed extract, 2g of L-arginine and 3g of vitamin C, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 4 preparation of the composition of the invention
Weighing 75g of corn starch, 10g of grape powder, 5g of grape seed extract, 5g of L-arginine and 5g of vitamin C, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 5 preparation of the composition of the invention
Weighing 75g of maltodextrin, 15g of grape powder, 1g of grape seed extract, 5g of L-arginine and 4g of vitamin E, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 6 preparation of a composition according to the invention
Weighing 75g of maltodextrin, 10g of grape powder, 10g of grape seed extract, 2g of L-arginine and 3g of vitamin E, and uniformly mixing to obtain the grape seed extract.
Example 7 preparation of a composition according to the invention
Weighing 75g of resistant dextrin, 5g of grape powder, 10g of grape seed extract, 5g of L-arginine and 5g of vitamin C, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 8 preparation of a composition of the invention
Weighing 85g of resistant dextrin, 5g of grape powder, 5g of grape seed extract, 2g of L-arginine and 3g of vitamin C, and uniformly mixing to obtain the grape seed extract.
Example 9 preparation of a composition according to the invention
Weighing 85g of maltodextrin, 10g of grape powder, 1g of grape seed extract, 2g of L-arginine and 2g of vitamin C, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 10 preparation of the composition of the invention
Weighing 65g of maltodextrin, 12g of grape powder, 10g of grape seed extract, 5g of L-arginine, 5g of vitamin C, 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 75g of maltodextrin, 10g of grape powder, 10g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 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 75g of maltodextrin, 15g of grape powder, 5g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 1g of citric acid, 1g of ethyl maltol and 1g of sucralose, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 13 preparation of a composition of the invention
Weighing 85g of maltodextrin, 10g of grape powder, 1g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 1g of citric acid, 0.5g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 14 preparation of a composition of the invention
Weighing 85g of maltodextrin, 10g of grape powder, 1g of grape seed extract, 1g of L-arginine, 1g of vitamin C, 1g of citric acid, 0.5g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 15 preparation of a composition of the invention
Weighing 77g of maltodextrin, 14g of grape powder, 5g of grape seed extract, 2g of L-arginine and 2g of vitamin C, and uniformly mixing to obtain the grape seed extract.
EXAMPLE 16 preparation of a composition of the invention
Weighing 92g of maltodextrin, 3g of proanthocyanidins, 1g of resveratrol, 2g of arginine and 2g of vitamin C, and uniformly mixing to obtain the traditional Chinese medicine.
EXAMPLE 17 preparation of a composition of the invention
Weighing 80g of maltodextrin, 5g of proanthocyanidins, 5g of resveratrol, 5g of arginine and 5g of vitamin C, and uniformly mixing to obtain the traditional Chinese medicine.
EXAMPLE 18 preparation of a composition of the invention
Weighing 80g of maltodextrin, 5g of proanthocyanidins, 5g of resveratrol, 5g of arginine and 5g of vitamin C, and uniformly mixing to obtain the traditional Chinese medicine.
EXAMPLE 19 preparation of a composition of the invention
Weighing 86g of maltodextrin, 3g of proanthocyanidins, 1g of resveratrol, 5g of arginine and 5g of vitamin C, and uniformly mixing to obtain the traditional Chinese medicine.
EXAMPLE 20 preparation of the composition of the invention
Weighing 90.5g of maltodextrin, 3g of proanthocyanidins, 0.68g of resveratrol, 2g of arginine, 2g of vitamin C, 1g of citric acid, 0.32g of ethyl maltol and 0.5g of sucralose, and uniformly mixing to obtain the traditional Chinese medicine composition.
EXAMPLE 21 preparation of a composition of the invention
Weighing 81g of maltodextrin, 5g of proanthocyanidins, 1g of resveratrol, 5g of arginine, 5g of vitamin C, 1g of citric acid, 1g of ethyl maltol and 1g of sucralose, and uniformly mixing to obtain the resveratrol-containing oral liquid.
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 C, 60g of maltodextrin, 1g of citric acid, 1g of ethyl maltol and 2g of sucralose, and uniformly mixing to obtain the grape powder.
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, uniformly mixing, and filling into capsules to obtain the oral liquid.
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 powder.
EXAMPLE 26 preparation of a composition of the invention
Weighing 20g of grape powder, 10g of grape seed extract, 1g of L-arginine, 1g 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 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 antioxidant effect of composition of the invention
1 materials and methods
75 SPF male ICR mice with weight of 25-28g provided by Beijing Wittingerhua laboratory animal technology company Limited are selected. At the end of the acclimation period, the animals were randomly divided into 5 groups of 15 animals each by body weight. Animal feeding management conditions: the mice are fed with the feed to maintain free intake of food and water, and the temperature of the animal room is 20-26 ℃ and the humidity is 40-70%.
The device comprises a multifunctional microplate reader, a centrifuge, a homogenizer, an electronic balance (sensitive O.Olg), an electronic balance (sensitive O.OOlg) and an ultraviolet spectrophotometer. Malondialdehyde (MDA) assay kit (Nanjing institute of technology), reduced Glutathione (GSH) assay kit (Nanjing institute of technology), Total Protein (TP) assay kit (Nanjing institute of technology), SOD kit (Nanjing institute of technology), and absolute ethanol (analytically pure, science of West Long).
500g of the pharmaceutical composition was weighed out and formulated with deionized water. The test animals are subjected to intragastric administration for 1 time every day for 30 days according to three dose groups, namely a low dose group (the administration dose is 0.4g/kg (body weight), a medium dose group (1.2 g/kg (body weight)) and a high dose group (the administration dose is 4.0g/kg (body weight)), a blank control group, a model control group (intragastric deionized water) and 20mL/kg (body weight)). Wherein, the model control group is perfused with gastric deionized water. The preparation method of the pharmaceutical composition comprises the following steps: weighing 14 parts of grape powder, 5 parts of grape seed extract, 2 parts of L-arginine and 2 parts of vitamin C, and uniformly mixing to obtain the grape seed extract.
After the last gavage, the model group control group and the three dose groups were fasted for 16h (overnight), then they were gavaged once more with 50% ethanol 12ml/kg (body weight), and after 6h the livers were sacrificed (blank control group was not treated, and was not fasted), and the MDA content, GSH content, and SOD activity, and body weight change (final weight-initial weight) were determined.
The test data is subjected to statistical analysis by using an EXCEL software to establish a database and an SPSS software.
2 results
2.1 Effect of animal body weight
As can be seen from FIG. 1, the body weight of mice in each dose group was changed (P >0.05) compared to the model control group by gavage of the mice with different doses of the pharmaceutical composition 30 d.
2.2 Effect of liver MDA content in mice
As can be seen from FIG. 2, the liver MDA content of the model control group was increased (P <0.01) compared to the blank control group by gavage administration of the pharmaceutical composition 30d to the mice at different doses. Compared with the model control group, the liver MDA content of each dose group is reduced (P < 0.01).
2.3 Effect on mouse liver SOD Activity
As can be seen in FIG. 3, the liver SOD activity of the model control group was decreased (P <0.05) compared to the blank control group when the mice were gavaged with the pharmaceutical composition at different doses for 30 d. Compared with a model control group, the liver tissue SOD activity of each dose group is high (P < 0.01).
2.4 Effect of mouse hepatic GSH content
As can be seen in fig. 4, the liver GSH of the model control group was reduced (P <0.05) compared to the blank control group by gavage of the mice given different doses of the pharmaceutical composition 30 d. The liver tissue GSH content of each dose group is increased compared with the model control group (P < 0.01).
Test example 2Study of the Lung injury-resisting Effect of the composition of the present invention
An HOPE-MED 8052 dust mouth-nose movable type contamination device is adopted to simulate the atmosphere pollution environment, and a rat model of fine particulate matter chronic contamination is constructed.
SPF grade SD rats (180-200 g) were purchased from Beijing Wittitonia organisms (48). The mouth and nose part is exposed in the contamination cabin, and the contamination cabin is provided with an air inlet system and an exhaust system. Putting a proper amount of fine particles into a powder box of equipment, atomizing the fine particles to the whole contamination cabin through an air inlet system, calculating the concentration and the contamination dose of the fine particles through a sampling system, and measuring the particle size distribution of inhalable particles in a contamination state.
The drug intervention is carried out while the infection is carried out, the drug administration is carried out for 1 time per day, the drug administration dose is 0.2g/kg, and the continuous infection and drug administration are carried out for 4 weeks and 8 weeks. One day prior to the end of the exposure period, fasted, anaesthetized with sodium pentobarbital (40mg/kg, i.p.), bled and sacrificed, and rat blood, alveolar lavage fluid and lung tissue were collected.
Setting a control group, a PM2.5 intervention group, a PM2.5+ grape powder group and a PM2.5+ pharmaceutical composition group. The preparation method of the pharmaceutical composition comprises the following steps: weighing 14 parts of grape powder, 5 parts of grape seed extract, 2 parts of L-arginine and 2 parts of vitamin C, and uniformly mixing to obtain the grape seed extract.
The protective effect of the composition of the invention on the overall toxicity of rats caused by PM2.5 is studied, the body weight of the rats is measured continuously for 8 weeks until the observation period is finished, and the body weight change results of each group are shown in figure 5.
The effect of the composition of the present invention on reduction of PM 2.5-induced lung inflammation was studied by measuring the number of rats, Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEUT), Eosinophils (EOS) and Basophils (BAS), and the results are shown in fig. 6.
The composition of the invention regulates the research of the expression change of the inflammation related gene caused by PM2.5, and the key mRNA in the lung tissue inflammatory reaction and the organism inflammatory reaction response caused by PM2.5 are measured, and the result is shown in figure 7.
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 is characterized in that 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 arginine is 0.5-10% (w/w), the content of vitamin C is 0.5-10% (w/w) and a pharmaceutically acceptable carrier.
2. The composition according to claim 1, wherein the content of grape powder in the composition is 5-20%, preferably 10-15% (w/w).
3. The composition according to any one of claims 1-2, wherein the resveratrol content in the grape powder is 1-10% (w/w), preferably 5-8% (w/w).
4. A composition according to any one of claims 1 to 3, wherein the content of the grape seed extract in the composition is 1-10% (w/w), preferably 2-5% (w/w).
5. The composition according to any one of claims 1 to 4, wherein the proanthocyanidin content in the grape seed extract is from 90 to 100% (w/w), preferably from 95 to 98% (w/w).
6. The composition according to any one of claims 1 to 5, wherein arginine is present in the composition in an amount of 1 to 5%, preferably 2 to 4% (w/w), and wherein vitamin C is present in an amount of 1 to 5%, preferably 2 to 4% (w/w).
7. The composition according to any one of claims 1 to 6, wherein the pharmaceutically acceptable carrier is selected from any one of a filler, a flavoring agent, or a combination thereof.
8. The composition of any one of claims 1 to 7, wherein the composition comprises 1 to 25% (w/w) of grape powder, 0.5 to 15% (w/w) of grape seed extract, 55 to 90% (w/w) of maltodextrin, 0.5 to 10% (w/w) of L-arginine, 0.5 to 10% of vitamin C and 0.5 to 5% (w/w) of a flavoring agent, wherein the flavoring agent is selected from any one or a combination of citric acid, ethyl maltol, grape essence and sucralose.
9. The process for the preparation of a pharmaceutical composition according to any one of claims 1 to 8, comprising in particular the steps of: uniformly mixing the required amount of grape powder, grape seed extract, arginine, vitamin C and pharmaceutically acceptable carrier to obtain the grape seed extract.
10. Use of a pharmaceutical composition according to any one of claims 1-8 for the manufacture of a preparation for the treatment of a patient suffering from lung injury or a patient suffering from hypoxia, preferably said lung injury is selected from any one of acute lung injury, inhaled lung injury, smoke induced lung injury, PM2.5 induced lung injury or a complication thereof.
CN202011410183.6A 2020-12-04 2020-12-04 Pharmaceutical composition with lung injury prevention and treatment effects and preparation method and application thereof Pending CN112451598A (en)

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