WO2022166847A1 - 一种组合物及其用途 - Google Patents

一种组合物及其用途 Download PDF

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WO2022166847A1
WO2022166847A1 PCT/CN2022/074766 CN2022074766W WO2022166847A1 WO 2022166847 A1 WO2022166847 A1 WO 2022166847A1 CN 2022074766 W CN2022074766 W CN 2022074766W WO 2022166847 A1 WO2022166847 A1 WO 2022166847A1
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acid
composition
mass percent
percent concentration
animal
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PCT/CN2022/074766
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English (en)
French (fr)
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崔德斌
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崔德斌
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Priority to US18/275,424 priority Critical patent/US20240082432A1/en
Publication of WO2022166847A1 publication Critical patent/WO2022166847A1/zh

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/02—Breeding vertebrates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/105—Aliphatic or alicyclic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/26—Compounds containing phosphorus
    • 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
    • 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
    • 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
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals

Definitions

  • the invention belongs to the technical field of life science, and relates to a composition and use thereof.
  • the pathogenesis of the disease can effectively cure the disease.
  • Cancer, cardiovascular and cerebrovascular diseases, and diabetes are the common diseases with the highest incidence in the world. With such a large incidence probability, we should be able to find out the regularity to break through the cause, and lay the foundation for drug screening and clinical research.
  • the present invention provides a composition and its use.
  • the composition of the present invention can be made into an animal model simulating various human diseases, so as to be used for preventing and treating human diseases and screening drugs.
  • the composition of the present invention is composed of sugar and acid/sugar, acid and alcohol.
  • the model animals are not limited to mammals.
  • the composition of the present invention is useful for the prevention and treatment of various human diseases such as diabetes, cancer, cardiovascular and cerebrovascular diseases, kidney diseases, and liver diseases. of great value.
  • the present invention is achieved through the following technical solutions.
  • the present invention provides a composition consisting of a sugar and an acid.
  • the sugar is a polyhydroxy (2 or more) aldehyde (Aldehyde) or ketone (Ketone) compound, which is composed of three elements, carbon, hydrogen and oxygen, preferably glucose.
  • Aldehyde aldehyde
  • Ketone ketone
  • the acid is an organic acid or an inorganic acid.
  • the acid is 85% (mass percent concentration) phosphoric acid, 37% (mass percent concentration) hydrochloric acid, 99.5% (mass percent concentration) acetic acid or 85% (mass percent concentration) lactic acid.
  • the mass-volume ratio between the sugar and the acid is 1:100-100:1 (g/mL), preferably 1:20-20:1 (g/mL), more preferably 1:0.375 ( g/mL) or 5:1 (g/mL).
  • the pH of the composition is below 4, preferably below 3.22;
  • the composition is a food composition.
  • the composition is: 1 g glucose+0.375 ml hydrochloric acid (37% (mass percent concentration));
  • the composition further comprises an alcohol, ie the composition consists of a sugar, an acid and an alcohol.
  • the alcohol is ethanol.
  • the ratio between the sugar, acid and alcohol is 1:100:1-100:1:100 (g/mL/mL), preferably 1:20:1-20:1:20 (g/mL) mL/mL), more preferably 10:5:5 (g/mL/mL).
  • the composition is a food composition
  • the food composition is a food that simulates the intake of a natural person in a normal diet.
  • the present invention provides a preparation method of the above composition, the preparation method includes mixing sugar and acid; or sugar, acid and alcohol in the aforementioned formula ratio.
  • the present invention provides the use of the above-mentioned composition in preparing an animal model, for example, the composition can induce cancer (eg, lung cancer) to be used as an inducer for preparing a cancer model.
  • cancer eg, lung cancer
  • the model animals used in the animal model include but are not limited to mammals, such as: mice, rats, rabbits, dogs, monkeys, cats, chickens, pigs and the like.
  • the animal model is administered to the model animal by various routes such as feeding, gavage, intravenous drip, intravenous injection or skin penetration of the composition.
  • the animal models include but are not limited to animal models of diabetes, various cancers, cardiovascular and cerebrovascular diseases caused by atherosclerosis and other diseases.
  • the animal model is used for drug screening for the prevention and/or treatment of cancer, diabetes, cardiovascular and cerebrovascular diseases caused by atherosclerosis and other diseases.
  • the present invention provides the use of an acid in the preparation of an animal model, eg, the acid can induce the production of cancer (eg, lung cancer), thereby serving as an inducer for the preparation of a cancer model.
  • cancer eg, lung cancer
  • the acid is an inorganic acid (eg hydrochloric acid) or an organic acid;
  • the acid is 13.88% (mass percent concentration) hydrochloric acid, 7.73% (mass percent concentration) lactic acid, 4.74-9.05% (mass percent concentration) acetic acid, 7.73% (mass percent concentration) phosphoric acid;
  • the pH of the acid is below 3.22.
  • the acid is:
  • the model animals used in the animal model include but are not limited to mammals, such as: mice, rats, rabbits, dogs, monkeys, cats, chickens, pigs, etc.;
  • the animal model is administered to the model animal by various routes such as feeding, gavage, intravenous drip, intravenous injection or skin penetration of the composition;
  • the animal models include, but are not limited to, animal models of diabetes, various cancers, atherosclerosis and cardiovascular and cerebrovascular diseases and other diseases caused by them.
  • the animal model is used for drug screening for the prevention and/or treatment of cancer, diabetes, atherosclerosis and cardiovascular and cerebrovascular diseases and other diseases caused by the same.
  • the present invention provides a method of modeling, the method comprising administering the aforementioned composition or acid to a model animal;
  • the model animals include but are not limited to mammals, such as: mice, rats, rabbits, dogs, monkeys, cats, chickens, pigs, etc.;
  • the established model is not limited to animal models of diabetes, various cancers (such as lung cancer), atherosclerosis and the cardiovascular and cerebrovascular diseases and other diseases it causes;
  • the acid is an inorganic acid (eg hydrochloric acid) or an organic acid;
  • the acid is 13.88% (mass percent concentration) hydrochloric acid, 7.73% (mass percent concentration) lactic acid, 4.74-9.05% (mass percent concentration) acetic acid, 7.73% (mass percent concentration) phosphoric acid;
  • the pH of the acid is below 4, preferably below 3.22.
  • the present invention has the following beneficial technical effects:
  • composition of the present invention is applied to the preparation of animal models, and provides a theoretical basis for the prevention and treatment of major diseases in humans.
  • the present invention completely simulates the normal eating habits of human beings to make animal disease models without other chemical substances, and is suitable for making animal models of various human diseases.
  • composition of the present invention is a precise animal model for screening human and/or animal drugs.
  • the present invention realizes rat and rabbit lung cancer animal models under the combined action of various acid and sugar-acid mixtures injected into the body by puncturing and injection. After the acid mixture is ingested, it will also enter into various tissues of the body through the circulatory system. Therefore, this model is not limited to a single lung cancer animal model, but also a general method for making various other cancer tissue models. That is to say, the various acids described in the present invention are And sugar-acid mixture can make all cancer animal models including leukemia.
  • animal models of other human diseases can also be made, because the long-term accumulation of aldehydes in the body will reduce the permeability of cell membranes, increase the transmembrane impedance, affect the normal metabolism of various cells, and lead to different tissue lesions.
  • aldehydes attached to the outer membrane of blood cells, after blood cell necrosis, it will deposit to form thrombosis, cardiovascular and cerebrovascular diseases, and attached to the outer membrane of pancreatic islet ⁇ cells, which will cause insulin secretion disorders and lead to diabetes.
  • organic and inorganic acids alone or in combination with glucose can create animal models of various human diseases.
  • Figure 1 Pathological staining results of control group 1 in experimental example 1 (10 ⁇ 10); the experiment was taken after 14 days, and the histopathological results of lung tissue of each rat, among which, 1: no cancer and mild inflammation; 2: no Cancer, bleeding; 3: No cancer, mild inflammation; 4: No cancer, mild inflammation; 5: No cancer, mild inflammation; 6: No cancer, mild inflammation;
  • Figure 2 Pathological staining results of control group 2 in experimental example 1 (10 ⁇ 10); the experimental protocol was originally expected to take materials on the 14th day, but the rats were in poor condition after injection, and the sixth one died early. Lung canceration was stably induced under the condition that the samples were collected in advance to 36h, and the experiment was ended. The following are the pathological analysis results of the rats in this group: 1: suspicious cancer; 2: no cancer; 3: no cancer; 4: no cancer; 5: No cancer was seen;
  • Figure 3 Pathological staining results of experimental group 1 in experimental example 1 (10 ⁇ 10); pathological analysis results after 96h (4d) injection of inducer: 1: adenocarcinoma, with few cancer glands; 2: adenocarcinoma, puncture point in Lung apex; 3: adenocarcinoma, few cancer glands; 4: adenocarcinoma, many cancer glands; 5: adenocarcinoma, many cancer glands; 6: adenocarcinoma, shallow puncture point, subpulmonary carcinoma;
  • FIG. 4 Pathological staining results of experimental group 2 in experimental example 1 (10 ⁇ 10); pathological analysis results after 168h (7d) injection of inducer: 1: adenocarcinoma; 2: adenocarcinoma; 3: adenocarcinoma; 4: adenocarcinoma; 5: Suspected adenocarcinoma, the diameter of the puncture point is about 3 mm; 6: Adenocarcinoma;
  • FIG. 6 Pathological staining results of test group 1 in experimental example 2 (10 ⁇ 10); the samples were taken after 14 days, and the pathological detection of each lung tissue was as follows: 1: no cancer, moderate inflammation; 2: no cancer, mild Inflammation; 3: No cancer, mild inflammation; 4: No cancer, mild inflammation; 5: No cancer, mild inflammation;
  • Fig. 7 Pathological staining results of test group 2 in experimental example 2 (10 ⁇ 10); the samples were taken after 7 days of the experiment, and the pathological detection of each lung tissue was as follows: 1: adenocarcinoma; 2: adenocarcinoma; 3: adenocarcinoma; 4: adenocarcinoma Carcinoma; 5: Adenocarcinoma;
  • FIG. 9 Pathological staining results of experimental group 4 in experimental example 2 (10 ⁇ 10); the samples were taken after 7 days of the experiment, and the pathological detection of each lung tissue was as follows: 1: adenocarcinoma; 2: adenocarcinoma; 3: adenocarcinoma; 4: adenocarcinoma Cancer; 5: No cancer, inflammatory secretions in the bronchial cavity, severe inflammation;
  • Fig. 10 The pathological staining results of test group 5 in experimental example 2 (10 ⁇ 10); the samples were taken after 7 days, and the pathological detection of each lung tissue was as follows: 1: adenocarcinoma; 2: adenocarcinoma, tumor necrosis with multinucleated giant cell reaction; 3: No cancer, severe inflammation; 4: No cancer, mild inflammation, no clear puncture point; 5: Adenocarcinoma, tumor cell necrosis;
  • Fig. 11 Pathological staining results (10 ⁇ 10) of experimental group 6 in experimental example 2; the samples were taken after 7 days of the experiment, and the pathological detection of each lung tissue was as follows: 1: adenocarcinoma; 2: no cancer, no puncture point; 3: Adenocarcinoma; 4: Death about 16 hours before taking materials in time; 5: Adenocarcinoma;
  • Fig. 12 Pathological staining results of test group 7 in experimental example 2 (10 ⁇ 10); the samples were taken after 7 days of the experiment, and the pathological tests of each lung tissue were as follows: 1: no cancer was found, and the puncture point was clear (death within 46 hours); 2: no See Carcinoma, mild inflammation; 3: Adenocarcinoma; 4: Adenocarcinoma; 5: Adenocarcinoma;
  • Fig. 13 Pathological staining results of test group 8 in experimental example 2 (10 ⁇ 10); the samples were taken after 7 days of the experiment, and the pathological examinations of each lung tissue were as follows: 1: No cancer, mild inflammation, and no clear puncture point; 2: glandular glands Carcinoma; 3: adenocarcinoma, focal alveolar epithelial atypical hyperplasia; 4: no cancer, focal alveolar epithelial atypical hyperplasia; 5: adenocarcinoma;
  • Fig. 14 Pathological staining results of test group 9 in experimental example 2 (10 ⁇ 10); the samples were taken after 7 days, and the pathological detection of each lung tissue was as follows: 1: adenocarcinoma; 2: adenocarcinoma, diaphragmatic muscle atrophy, fibrous tissue hyperplasia; 3 : adenocarcinoma; 4: adenocarcinoma; 5: adenocarcinoma;
  • Fig. 15 Pathological staining results (10 ⁇ 10) of test group 10 in experimental example 2; the samples were taken after 7 days, and the pathological detection of each lung tissue was as follows: 1: no cancer; 2: adenocarcinoma; 3: adenocarcinoma; 4: Adenocarcinoma; 5: Adenocarcinoma, see tumor necrosis.
  • Acetic acid ( ⁇ 99.5%), Sinopharm Chemical Reagent Co., Ltd., batch number: 20160920.
  • Example 1 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose with acetic acid mL uniformly and then use it for later use.
  • Example 2 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose with 2 mL of acetic acid and then use it for later use.
  • Example 3 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose with 3 mL of acetic acid and then use it for later use.
  • Example 4 Composition of the present invention
  • Preparation method mix 10 g of formula glucose and 4 mL of acetic acid evenly and then use it for later use.
  • Example 5 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose and 5 mL of acetic acid evenly and then use it for later use.
  • Example 6 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose and 6 mL of acetic acid evenly and then use it for later use.
  • Example 7 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose and 7 mL of acetic acid evenly, and then use it for later use.
  • Example 8 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose and 8 mL of acetic acid evenly, and then use it for later use.
  • Example 9 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose and 9 mL of acetic acid evenly and then use it for later use.
  • Example 10 Composition of the present invention
  • Preparation method Mix 10 g of formula glucose and 10 mL of acetic acid evenly and then use it for later use.
  • Example 11 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 1 mL of acetic acid, and 1 mL of ethanol evenly for use.
  • Example 12 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 2 mL of acetic acid, and 2 mL of ethanol evenly for use.
  • Example 13 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 3 mL of acetic acid, and 3 mL of ethanol evenly for use.
  • Example 14 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 4 mL of acetic acid, and 4 mL of ethanol evenly for use.
  • Example 15 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 5 mL of acetic acid, and 5 mL of ethanol evenly for later use.
  • Example 16 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 6 mL of acetic acid, and 6 mL of ethanol evenly for use.
  • Example 17 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 7 mL of acetic acid, and 7 mL of ethanol evenly for later use.
  • Example 18 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 8 mL of acetic acid, and 8 mL of ethanol evenly for use.
  • Example 19 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 9 mL of acetic acid, and 9 mL of ethanol evenly for use.
  • Example 20 Composition of the present invention
  • Preparation method Mix 10 g of glucose, 10 mL of acetic acid, and 10 mL of ethanol evenly, and then use it for later use.
  • composition of the present invention induces the formation of lung cancer in a rat model at different time points.
  • Age or weight 200g ⁇ 20g
  • the temperature of the rearing room is 18-22°C, the humidity is 40-70%, the ventilation frequency is not less than 20 times/h, and no more than 6 animals are raised in each cage, and the light is alternated between light and dark for 12 hours.
  • Animals were given qualified rat feed, and the animals were free to eat. Animals were given purified water, which was supplied with drinking bottles and freely ingested.
  • mice were divided into 5 groups according to body weight, with 6 animals in each group.
  • the conditions and doses of the inducers given to the animals in each group are as follows:
  • the preparation method of the inducer in the above table is: add 1g of glucose to 0.375ml of hydrochloric acid, heat and stir at low temperature until it becomes a colorless and transparent viscous liquid.
  • the rats were anesthetized with isoflurane, the left armpit of the rat was shaved to prepare the skin, iodine was sterilized, and 50 ⁇ L of the modeling drug was drawn with a microsyringe.
  • the angle between the ribs behind the elbow joint of the left forelimb and the horizontal plane was 45°, and the needle was inserted at a depth of 1 cm, and then it could enter the lung.
  • Chloral hydrate was injected intravenously, the rats were anesthetized and killed, the thoracic cavity was opened, and the lesions at the drug site were observed according to the site of drug administration in the lungs.
  • Microscope photography reading.
  • the temperature of the rearing room was 18-22°C, the humidity was 40-70%, the ventilation frequency was not less than 20 times/h, and no more than 2 animals were kept in each cage, and the light was alternated between light and dark for 12 hours. Animals were given qualified feed, and the animals were free to eat. Animals were given purified water, which was supplied with drinking bottles and freely ingested.
  • the model preparation method is as follows: using random grouping method, animals are divided into 10 groups according to body weight, and each group has 5 animals.
  • the conditions and doses of inducers administered to animals in each group are as follows:
  • the experimental rabbit was placed on its side and restrained, the left side was up, the left armpit was shaved and the skin was prepared, sterilized with iodophor, and its ribs were counted forward from the lower edge of the rib, between the 7th and 8th ribs, 2 finger widths away from the spine. Insert the needle, suck 300uL of the modeling medicine with a 1mL syringe, and the depth of the needle insertion is the whole of the needle of the syringe, about 2.5cm, and the medicine can be injected into the lungs.
  • Chloral hydrate was injected intravenously, the experimental rabbits were anesthetized and killed, the thoracic cavity was opened, and the lesions at the drug administration site were observed according to the lung administration site, and the materials were fixed, dehydrated, embedded, sliced, spread, baked, and put into xylene.

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Abstract

一种组合物及其用途，该组合物由糖和酸或者糖、酸和醇组成，可以制作成模拟人的多种疾病的动物模型，从而用于预防、治疗人类疾病和筛选药物。

Description

一种组合物及其用途 技术领域
本发明属于生命科学技术领域，涉及一种组合物及其用途。
背景技术
目前人类对疾病的认识是随社会发展和科技进步不断提高的，当前许多重大疾病和慢性病几乎都难以治愈，其中大部分疾病只能维持、缓解，控制缓慢发展，从全球来看，癌症、心脑血管疾病、糖尿病等是除传染性疾病以外致死率最高也是最常见的疾病，医药、科研人员都在积极努力突破现有技术，期待早日实现完全彻底解决这些危及人类生命的重大疾病和慢性病。近百年来，虽然对各种疾病的研究和认识不断提高，但主要的关键问题还是没有解决，找不到病因，只能对症治疗，如果从病因学方面入手就会很快得以解决，只有明确疾病的发病机制，才能有效治愈疾病。癌症、心脑血管疾病、糖尿病是世界发病率最高的常见病，这样大的发病概率我们应该能找出规律突破病因，为药物筛选和临床研究奠定基础。
为了满足药物筛选和临床的需要，采用准确的完全模拟人类在正常饮食生活习惯中制作的动物疾病模型是决定药物筛选的成败关键所在，同时对人类预防和治愈这些疾病发挥重要作用。
发明内容
为了解决现有技术存在的问题，本发明提供一种组合物及其用途，本发明的组合物可以制作成模拟人的多种疾病的动物模型，从而用于预防、治疗人类疾病和筛选药物。本发明的组合物由糖和酸/糖、酸和醇组成，模型动物不限于哺乳动物，本发明的组合物对于糖尿病、癌症、心脑血管疾病、肾病、肝病等人类多种疾病预防和治疗具有重大价值。
本发明是通过如下技术方案来实现的。
一方面，本发明提供一种组合物，该组合物由糖和酸组成。
优选地，所述糖是多羟基(2个或以上)的醛类(Aldehyde)或酮类(Ketone)化合物，由碳、氢、氧三种元素构成，优选为葡萄糖。
优选地，所述酸为有机酸或无机酸。
优选地，所述酸为85％(质量百分浓度)磷酸、37％(质量百分浓度盐酸、99.5％(质量百分浓度)乙酸或85％(质量百分浓度)乳酸。
优选地，所述糖与酸之间的质量体积比为1:100-100:1(g/mL)，优选为1:20-20:1(g/mL)，更优选为1:0.375(g/mL)或5:1(g/mL)。
优选地，所述组合物的pH值低于4，优选低于3.22；
优选地，所述组合物为食物组合物。
在一个具体的实施方案中，所述组合物为：1g葡萄糖+0.375ml盐酸(37％(质量百分浓度))；
50％(质量百分浓度)葡萄糖注射液与乙酸(99.5％(质量百分浓度))混合液(体积比10:1)；
50％葡萄糖注射液与乙酸(99.5％(质量百分浓度))混合液(体积比20:1)；
50％葡萄糖注射液与乳酸(85％(质量百分浓度))混合液(体积比10:1)；
50％葡萄糖注射液与磷酸(85％(质量百分浓度))混合液(体积比10:1)。优选地，所述组合物还包括醇，即所述组合物由糖、酸与醇组成。
优选地，所述醇为乙醇。
优选地，所述糖、酸与醇之间的比例为1:100:1-100:1:100(g/mL/mL)，优选为1:20:1-20:1:20(g/mL/mL)，更优选为10:5:5(g/mL/mL)。
优选地，所述组合物为食物组合物，在本申请中，所述食物组合物是模拟自然人在正常饮食中所摄入的食物。
另一方面，本发明提供一种上述组合物的制备方法，该制备方法包括将糖和酸；或者糖、酸和醇以前述的配方比例进行混合，即可。
再一方面，本发明提供上述组合物在制备动物模型中的用途，例如所述组合物可以诱导癌症(例如肺癌)产生，从而作为制备癌症模型的诱导剂。
优选地，所述动物模型中使用的模型动物包括但不限于哺乳动物，如：小鼠、大鼠、兔、狗、猴、猫、鸡、猪等。
优选地，所述动物模型通过将所述组合物饲喂、灌胃、静脉滴注、静脉注射或皮肤渗透等多种途径施用于所述模型动物。
优选地，所述动物模型包括但不限于糖尿病、各种癌症、动脉粥样硬化导致的心脑血管疾病及其它疾病的动物模型。
优选地，所述动物模型用于预防和/或治疗癌症、糖尿病、动脉粥样硬化导致的心脑血管疾病及其它疾病的药物筛选。
又一方面，本发明提供酸在制备动物模型中的用途，例如所述酸可以诱导癌症(例如肺癌)产生，从而作为制备癌症模型的诱导剂。
优选地，所述酸为无机酸(例如盐酸)或有机酸；
优选地，所述酸为13.88％(质量百分浓度)盐酸、7.73％(质量百分浓度)乳酸、4.74-9.05％(质量百分浓度)乙酸、7.73％(质量百分浓度)磷酸；
优选地，所述酸的pH值低于3.22。
在一个具体的实施方案中，所述酸为：
生理盐水与浓盐酸(37％(质量百分浓度))混合液(体积比5：3)；
生理盐水与乙酸(99.5％(质量百分浓度))混合液(体积比10：1)；
生理盐水与乳酸(85％(质量百分浓度))混合液(体积比10：1)；
生理盐水与磷酸(85％(质量百分浓度))混合液(体积比10：1)；
生理盐水(10mL)与乙酸(99.5％(质量百分浓度))(1mL)混合液；
生理盐水(10mL)与乙酸(99.5％(质量百分浓度))(0.5mL)混合液；
生理盐水(10mL)与乳酸(85％(质量百分浓度))(1mL)混合液；
生理盐水(10mL)与磷酸(85％(质量百分浓度))(1mL)混合液；
生理盐水(2.5mL)与盐酸(37％(质量百分浓度))(1.5mL)混合液。
优选地，所述动物模型中使用的模型动物包括但不限于哺乳动物，如：小鼠、大鼠、兔、狗、猴、猫、鸡、猪等；
优选地，所述动物模型通过将所述组合物饲喂、灌胃、静脉滴注、静脉注射或皮肤渗透等多种途径施用于所述模型动物；
优选地，所述动物模型包括但不限于糖尿病、各种癌症、动脉粥样硬化和其导致的心脑血管疾病及其它疾病的动物模型。
优选地，所述动物模型用于预防和/或治疗癌症、糖尿病、动脉粥样硬化和其导致的心脑血管疾病及其它疾病的药物筛选。
再又一方面，本发明提供一种建模的方法，该方法包括向模型动物施用前述的组合物或酸；
优选地，所述模型动物包括但不限于哺乳动物，如：小鼠、大鼠、兔、狗、猴、猫、鸡、猪等；
优选地，建立的模型不限于糖尿病、各种癌症(例如肺癌)、动脉粥样 硬化和其导致的心脑血管疾病及其它疾病的动物模型；
优选地，所述酸为无机酸(例如盐酸)或有机酸；
优选地，所述酸为13.88％(质量百分浓度)盐酸、7.73％(质量百分浓度)乳酸、4.74-9.05％(质量百分浓度)乙酸、7.73％(质量百分浓度)磷酸；
优选地，所述酸的pH值低于4，优选低于3.22。
与现有技术相比较，本发明具有如下有益的技术效果：
(1)本发明的组合物应用于制备动物模型，为人类预防、治疗重大疾病提供理论依据。
(2)本发明完全模拟人类正常饮食生活习惯制作的动物疾病模型，无需其它化学物质，适用制作多种人类疾病的动物模型。
(3)本发明组合物是筛选人和/或动物用药物的精准动物模型。
当前，国内外研究已经证明炎症会诱发癌症。在本发明中，所述糖与酸是所有动物生命体存在所必须的，不可否认的是两者进入体内后除机体正常代谢需要外，有部分还会形成醛类化合物附着在细胞外膜，当组织出现炎症时，并附着在细胞外膜的醛类化合物达到阈值时就会使炎症点位细胞坏死，坏死后的醛类化合物形成堆积，更加剧细胞坏死及浸润正常组织细胞，逐渐形成坏死点、结节、小肿块、肿瘤。在本发明中可见穿刺点都见炎症，癌变处也见不同程度坏死，与注入的液体导致刺激性坏死不同，多个模型病理图片可见注入的液体在组织间快速坏死、水肿、纤维组织增生、伴癌、癌组织形成，癌变处也见不同程度坏死在癌组织形成时是可见的，并非注射液体形成刺激性坏死，从液体注入至癌组织形成这个过程一般在96小时完成，而后肿瘤组织继续生长。因此，本发明在穿刺和注射进入体内的多种酸和糖酸混合物共同作用下，实现了大鼠和兔肺癌动物模型，总所周知，炎症可以出现在机体多个组织，多种酸及糖酸混合物摄入后通过循环系统也会进入机体各个组织，所以，这种模型并非限于单独的肺癌动物模型，也是其它各种癌症组织模型的制作通用方法，也就是说本发明所述各种酸及糖酸混合物可以制作全部癌症动物模型包括白血病。
除制作癌症动物模型外也可以制作人类其它多种疾病动物模型，因为醛类化合物在体内长期蓄积会使细胞膜通透性降低，跨膜阻抗增大，影响各种细胞正常代谢，导致不同组织病变，例如：附着在血细胞外膜，血细胞坏死后就会沉积形成血栓、心脑血管疾病，附着在胰腺胰岛β细胞外膜，会使胰 岛素分泌障碍，导致糖尿病。因此，有机酸和无机酸单独或与葡萄糖组合物可以制作多种人类疾病的动物模型。
附图说明
图1：实验例1中对照组1病理染色结果(10×10)；实验为14d后取材，各大鼠肺组织病理学结果，其中，1：未见癌、轻度炎症；2：未见癌、出血；3：未见癌、轻度炎症；4：未见癌、轻度炎症；5：未见癌、轻度炎症；6：未见癌、轻度炎症；
图2：实验例1中对照组2病理染色结果(10×10)；实验方案原预计第14d取材，大鼠注射后状态不佳，其中第6只提前死亡，预期次配方不能在大鼠健康情况下稳定诱导肺部癌变，随提前至36h取材，结束实验，以下为本组大鼠病理分析结果：1：可疑癌；2：未见癌；3：未见癌；4：未见癌；5：未见癌；
图3：实验例1中实验组1病理染色结果(10×10)；诱导剂注射96h(4d)后病理分析结果为：1：腺癌，癌腺体少；2：腺癌，穿刺点在肺尖处；3：腺癌，癌腺体少；4：腺癌，癌腺体多；5：腺癌，癌腺体多；6：腺癌，穿刺点浅，肺膜下癌；
图4实验例1中实验组2病理染色结果(10×10)；诱导剂注射168h(7d)后病理分析结果：1：腺癌；2：腺癌；3：腺癌；4：腺癌；5：可疑腺癌，穿刺点直径约3毫米；6：腺癌；
图5实验例1中实验组3病理染色结果(10×10)；诱导剂注射336h(14d)后病理分析结果：1：腺癌，肉芽肿性炎症；2：未见癌，肉芽肿性炎症，穿刺点表浅；3：未见癌，穿刺点2毫米；4：未见癌，未见穿刺点；5：腺癌，轻度炎症；6：腺癌，未见明确穿刺点，肺内出血严重，肺膜下癌；
图6实验例2中试验组1病理染色结果(10×10)；实验为14d后取材，各肺组织病理学检测如下：1：未见癌，中度炎症；2：未见癌，轻度炎症；3：未见癌，轻度炎症；4：未见癌，轻度炎症；5：未见癌，轻度炎症；
图7实验例2中试验组2病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：腺癌；2：腺癌；3：腺癌；4：腺癌；5：腺癌；
图8实验例2中试验组3病理染色结果(10×10)；实验为7d后取材， 各肺组织病理学检测如下：1：大约12小时死亡未及时取材；2：腺癌；3：腺癌；4：未见癌，穿刺点周围见肺泡上皮不典型增生；5：腺癌；
图9实验例2中试验组4病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：腺癌；2：腺癌；3：腺癌；4：腺癌；5：未见癌，支气管腔内炎性分泌物，重度炎症；
图10实验例2中试验组5病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：腺癌；2：腺癌，肿瘤坏死伴多核巨细胞反应；3：未见癌，重度炎症；4：未见癌，轻度炎症未见明确穿刺点；5：腺癌，见肿瘤细胞坏死；
图11实验例2中试验组6病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：腺癌；2：未见癌，未见穿刺点；3：腺癌；4：大约16小时死亡未及时取材；5：腺癌；
图12实验例2中试验组7病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：未见癌，穿刺点明确(46小时死亡)；2：未见癌，轻度炎症；3:腺癌；4：腺癌；5：腺癌；
图13实验例2中试验组8病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：未见癌轻度炎症，未见明确穿刺点；2：腺癌；3：腺癌，局灶见肺泡上皮不典型增生；4：未见癌，局灶见肺泡上皮不点型增生；5：腺癌；
图14实验例2中试验组9病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：腺癌；2：腺癌，膈肌萎缩，纤维组织增生；3：腺癌；4：腺癌；5：腺癌；
图15实验例2中试验组10病理染色结果(10×10)；实验为7d后取材，各肺组织病理学检测如下：1：未见癌；2：腺癌；3：腺癌；4：腺癌；5：腺癌，见肿瘤坏死。
具体实施方式
下面结合具体实施方式对本发明进行进一步的详细描述，给出的实施例仅为了阐明本发明，而不是为了限制本发明的范围。
下述实施例中的实验方法，如无特殊说明，均为常规方法。下述实施例中所用的药材原料、试剂材料等，如无特殊说明，均为市售购买产品。
以下实施例中实验材料、来源如下：
葡萄糖：(≥99.5％)，国药集团化学试剂有限公司、批号：20140821。
乙酸：(≥99.5％)，国药集团化学试剂有限公司、批号：20160920。
乙醇：(≥95％)，国药集团化学试剂有限公司、批号：20200810。
实施例1本发明的组合物
配方：葡萄糖10g乙酸1mL；
制备方法：将配方葡萄糖10g乙酸mL混合均匀后备用。
实施例2本发明的组合物
配方：葡萄糖10g乙酸2mL；
制备方法：将配方葡萄糖10g乙酸2mL混合均匀后备用。
实施例3本发明的组合物
配方：葡萄糖10g乙酸3mL；
制备方法：将配方葡萄糖10g乙酸3mL混合均匀后备用。
实施例4本发明的组合物
配方：葡萄糖10g乙酸4mL；
制备方法：将配方葡萄糖10g乙酸4mL混合均匀后备用。
实施例5本发明的组合物
配方：葡萄糖10g乙酸5mL；
制备方法：将配方葡萄糖10g乙酸5mL混合均匀后备用。
实施例6本发明的组合物
配方：葡萄糖10g乙酸6mL；
制备方法：将配方葡萄糖10g乙酸6mL混合均匀后备用。
实施例7本发明的组合物
配方：葡萄糖10g乙酸7mL；
制备方法：将配方葡萄糖10g乙酸7mL混合均匀后备用。
实施例8本发明的组合物
配方：葡萄糖10g乙酸8mL；
制备方法：将配方葡萄糖10g乙酸8mL混合均匀后备用。
实施例9本发明的组合物
配方：葡萄糖10g乙酸9mL；
制备方法：将配方葡萄糖10g乙酸9mL混合均匀后备用。
实施例10本发明的组合物
配方：葡萄糖10g乙酸10mL；
制备方法：将配方葡萄糖10g乙酸10mL混合均匀后备用。
实施例11本发明的组合物
配方：葡萄糖10g、乙酸1mL、乙醇1mL
制备方法：将葡萄糖10g、乙酸1mL、乙醇1mL混合均匀后备用。
实施例12本发明的组合物
配方：葡萄糖10g、乙酸2mL、乙醇2mL
制备方法：将葡萄糖10g、乙酸2mL、乙醇2mL混合均匀后备用。
实施例13本发明的组合物
配方：葡萄糖10g、乙酸3mL、乙醇3mL
制备方法：将葡萄糖10g、乙酸3mL、乙醇3mL混合均匀后备用。
实施例14本发明的组合物
配方：葡萄糖10g、乙酸4mL、乙醇4mL
制备方法：将葡萄糖10g、乙酸4mL、乙醇4mL混合均匀后备用。
实施例15本发明的组合物
配方：葡萄糖10g、乙酸5mL、乙醇5mL
制备方法：将葡萄糖10g、乙酸5mL、乙醇5mL混合均匀后备用。
实施例16本发明的组合物
配方：葡萄糖10g、乙酸6mL、乙醇6mL
制备方法：将葡萄糖10g、乙酸6mL、乙醇6mL混合均匀后备用。
实施例17本发明的组合物
配方：葡萄糖10g、乙酸7mL、乙醇7mL
制备方法：将葡萄糖10g、乙酸7mL、乙醇7mL混合均匀后备用。
实施例18本发明的组合物
配方：葡萄糖10g、乙酸8mL、乙醇8mL
制备方法：将葡萄糖10g、乙酸8mL、乙醇8mL混合均匀后备用。
实施例19本发明的组合物
配方：葡萄糖10g、乙酸9mL、乙醇9mL
制备方法：将葡萄糖10g、乙酸9mL、乙醇9mL混合均匀后备用。
实施例20本发明的组合物
配方：葡萄糖10g、乙酸10mL、乙醇10mL
制备方法：将葡萄糖10g、乙酸10mL、乙醇10mL混合均匀后备用。
实验例1本发明的组合物诱导大鼠形成肺癌的研究
1.实验目的：
试验并验证本发明的组合物不同时间点在大鼠模型上诱导形成肺部癌变的情况。
2.材料与方法
2.1实验材料与试剂
2.1.1主要实验试剂：
Figure PCTCN2022074766-appb-000001
Figure PCTCN2022074766-appb-000002
2.1.2主要实验设备：
Figure PCTCN2022074766-appb-000003
2.2实验动物
种属&品系：SD大鼠；
动物等级：SPF级；
性别：雄性；
实验动物来源：辽宁长生生物技术股份有限公司；
日龄或体重：200g±20g；
数量：30只；
2.3实验方法
2.3.1实验动物饲养：
饲养室温度18-22℃，湿度40-70％，换气次数不少于20次/h，每笼饲养不超过6只，光照12小时明暗交替。动物给予合格的鼠料，动物均自由摄食。动物给予纯化水，用饮水瓶供应，自由摄水。
2.3.2诱导注射：
实验动物分组及给药情况如下：
采用随机分组法，根据体重将动物分为5组，每组6只动物。各组动物给于诱导剂情况及剂量如下表：
Figure PCTCN2022074766-appb-000004
注：上表中诱导剂制备方法为：1g葡萄糖加入到0.375ml盐酸中，低温加热搅拌至无色透明状黏稠性液体。
异氟烷将大鼠麻醉，在大鼠的左侧腋窝剃毛备皮，碘伏消毒，用微量注射器吸取50μL造模药物，大鼠侧卧，左侧向上，左前肢自然弯曲，在大鼠 左前肢肘关节侧后方的肋骨之间与水平面夹角为45°进针，深度为1cm，即可进入肺部，注射50μL造模药物，分别在不同时间点检测肺癌模型形成情况。
2.3.3病理检测：
静脉注射水合氯醛，麻醉处死大鼠，剖开胸腔，根据肺给药部位，观察给药部位病变，并取材固定，经程序化脱水、包埋、切片、摊片、烤片，入二甲苯中脱蜡5分钟×3次，100％乙醇2分钟×2次，自来水冲洗2分钟，苏木素染色3分钟，自来水2分钟，1％盐酸酒精溶液分化2秒，自来水冲洗2分钟，返兰液1秒，自来水2分钟，伊红染色10秒，50％乙醇脱水10秒，70％乙醇脱水10秒，无水乙醇1分钟×2次，二甲苯中透明3分钟×2次，中性树胶封片。显微镜拍照，阅片。
2.4实验结果
各实验组HE病理染色结果如图1-至图5。
3结论
由本研究可知，对照组1葡萄糖和生理盐水未能诱导癌变，对照组2生理盐水和盐酸毒性较强、短时间内未见明确诱导癌变，而诱导剂在优化配比之后，实验组在在第4d即检测出注射区域出现癌变，且7d及14d病理检测进一步证实了诱导剂诱导大鼠肺部出现腺癌癌变的效果。证明该种方式配制的诱导剂可在短期内诱导大鼠肺部癌变。
实验例2本发明的组合物诱导兔肺组织形成癌变的研究
1.实验目的：
试验并验证本发明的组合物不同时间点、在实验兔模型上诱导形成肺部癌变的情况。
2.材料与方法
2.1实验材料与试剂
2.1.1主要实验试剂：
Figure PCTCN2022074766-appb-000005
Figure PCTCN2022074766-appb-000006
2.1.2主要实验设备：
Figure PCTCN2022074766-appb-000007
2.2实验动物
种属&品系：新西兰白兔；
动物等级：SPF级；
性别：雄性；
实验动物来源：中国食品药品检定研究院；
日龄或体重：1.8～2.2kg；
数量：50只；
2.3实验方法
2.3.1实验动物饲养：
饲养室温度18-22℃，湿度40-70％，换气次数不少于20次/h，每笼饲养不超过2只，光照12小时明暗交替。动物给予合格的饲料，动物均自由摄食。动物给予纯化水，用饮水瓶供应，自由摄水。
2.3.2诱导注射:
模型制备方法如下：采用随机分组法，根据体重将动物分为10组，每组5只动物。各组动物给予诱导剂情况及剂量如下表：
Figure PCTCN2022074766-appb-000008
Figure PCTCN2022074766-appb-000009
将实验兔侧卧保定，左侧向上，在左侧腋窝剃毛备皮，碘伏消毒，从肋骨下缘向前数其肋骨，在第7-8肋骨之间，距离脊柱2指宽的位置进针，1mL注射器吸取造模药物300uL，进针深度为注射器针头的全部，约2.5cm，即可将药物注射入肺部。
2.3.3病理检测：
静脉注射水合氯醛，麻醉处死实验兔，剖开胸腔，根据肺给药部位，观察给药部位病变，并取材固定，经程序化脱水、包埋、切片、摊片、烤片，入二甲苯中脱蜡5分钟×3次，100％乙醇2分钟×2次，自来水冲洗2分钟，苏木素染色3分钟，自来水2分钟，1％盐酸酒精溶液分化2秒，自来水冲洗2分钟，返兰液1秒，自来水2分钟，伊红染色10秒，50％乙醇脱水10秒，70％乙醇脱水10秒，无水乙醇1分钟×2次，二甲苯中透明3分钟×2次，中性树胶封片。显微镜拍照，阅片。
2.4实验结果
各实验组HE病理染色结果如图6至图15。
3结论
由本研究可知，除实验组1对照组外，其余各组组方均可以在7d内诱导出癌变，更进一步的兼顾安全性及诱导效率，实验组2组方(生理盐水与浓盐酸混合液(体积比5:3))及实验组9组方(50％葡萄糖注射液与乳酸混合液(体积比10:1))最优。组方中加入葡萄糖可有效降低局部的急性刺激程度，减少实验动物死亡。

Claims (11)

  1. 一种组合物，该组合物由糖和酸组成。
  2. 根据权利要求1所述的组合物，其中，所述糖是多羟基(2个或以上)的醛类(Aldehyde)或酮类(Ketone)化合物，由碳、氢、氧三种元素构成，优选为葡萄糖；
    优选地，所述酸为有机酸或无机酸；
    优选地，所述酸为85％(质量百分浓度)磷酸、37％(质量百分浓度盐酸、99.5％(质量百分浓度)乙酸或85％(质量百分浓度)乳酸；
    优选地，所述糖与酸之间的质量体积比为1:100-100:1(g/mL)，优选为1:20-20:1(g/mL)，更优选为1:0.375(g/mL)或5:1(g/mL)；优选地，所述组合物的pH值低于4，优选低于3.22；
    优选地，所述组合物为食物组合物。
  3. 一种组合物，该组合物由糖、酸与醇组成。
  4. 根据权利要求3所述的组合物，其中，所述醇为乙醇；
    优选地，所述糖、酸与醇之间的比例为1:100:1-100:1:100(g/mL/mL)，优选为1:20:1-20:1:20(g/mL/mL)，更优选为10:5:5(g/mL/mL)；
    优选地，所述组合物为食物组合物。
  5. 权利要求1至4中任一项所述的组合物在制备动物模型中的用途。
  6. 根据权利要求5所述的用途，其中，所述动物模型中使用的模型动物包括但不限于哺乳动物，如：小鼠、大鼠、兔、狗、猴、猫、鸡、猪等；
    优选地，所述动物模型通过将所述组合物饲喂、灌胃、静脉滴注、静脉注射或皮肤渗透等多种途径施用于所述模型动物；
    优选地，所述动物模型包括但不限于糖尿病、各种癌症、动脉粥样硬化和其导致的心脑血管疾病及其它疾病的动物模型。
  7. 根据权利要求5所述的用途，其中，所述动物模型用于预防和/或治疗癌症、糖尿病、动脉粥样硬化和其导致的心脑血管疾病及其它疾病的药物筛选。
  8. 酸在制备动物模型中的用途，优选地，所述酸为无机酸(例如盐酸)或有机酸；
    优选地，所述酸为13.88％(质量百分浓度)盐酸、7.73％(质量百分浓 度)乳酸、4.74-9.05％(质量百分浓度)乙酸、7.73％(质量百分浓度)磷酸；
    优选地，所述酸的pH值低于4，优选低于3.22。
  9. 根据权利要求8所述的用途，其中，所述动物模型中使用的模型动物包括但不限于哺乳动物，如：小鼠、大鼠、兔、狗、猴、猫、鸡、猪等；
    优选地，所述动物模型通过将所述组合物饲喂、灌胃、静脉滴注、静脉注射或皮肤渗透等多种途径施用于所述模型动物；
    优选地，所述动物模型包括但不限于糖尿病、各种癌症、动脉粥样硬化和其导致的心脑血管疾病及其它疾病的动物模型。
  10. 根据权利要求8所述的用途，其中，所述动物模型用于预防和/或治疗癌症、糖尿病、动脉粥样硬化和其导致的心脑血管疾病及其它疾病的药物筛选。
  11. 一种建模的方法，该方法包括向模型动物施用权利要求1至4中任一项所述的组合物或酸；
    优选地，所述模型动物包括但不限于哺乳动物，如：小鼠、大鼠、兔、狗、猴、猫、鸡、猪等；
    优选地，建立的模型不限于糖尿病、各种癌症、动脉粥样硬化和其导致的心脑血管疾病及其它疾病的动物模型；
    优选地，所述酸为无机酸(例如盐酸)或有机酸；
    优选地，所述酸为13.88％(质量百分浓度)盐酸、7.73％(质量百分浓度)乳酸、4.74-9.05％(质量百分浓度)乙酸、7.73％(质量百分浓度)磷酸；
    优选地，所述酸的pH值低于4，优选低于3.22。
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