WO2016000637A1 - 一种降血脂组合物及其应用 - Google Patents

一种降血脂组合物及其应用 Download PDF

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WO2016000637A1
WO2016000637A1 PCT/CN2015/083178 CN2015083178W WO2016000637A1 WO 2016000637 A1 WO2016000637 A1 WO 2016000637A1 CN 2015083178 W CN2015083178 W CN 2015083178W WO 2016000637 A1 WO2016000637 A1 WO 2016000637A1
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Prior art keywords
ornithine
acid
composition
vitamin
aspartic acid
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PCT/CN2015/083178
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English (en)
French (fr)
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万红贵
岳茂兴
Original Assignee
万红贵
岳茂兴
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Application filed by 万红贵, 岳茂兴 filed Critical 万红贵
Priority to EP15815344.5A priority Critical patent/EP3165221B1/en
Priority to US15/551,031 priority patent/US20180028543A1/en
Priority to ES15815344T priority patent/ES2861023T3/es
Publication of WO2016000637A1 publication Critical patent/WO2016000637A1/zh

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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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A21—BAKING; EDIBLE DOUGHS
    • A21D—TREATMENT, e.g. PRESERVATION, OF FLOUR OR DOUGH, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS; PRESERVATION THEREOF
    • A21D2/00—Treatment of flour or dough by adding materials thereto before or during baking
    • A21D2/08—Treatment of flour or dough by adding materials thereto before or during baking by adding organic substances
    • A21D2/24—Organic nitrogen compounds
    • A21D2/245—Amino acids, nucleic acids
    • A—HUMAN NECESSITIES
    • A21—BAKING; EDIBLE DOUGHS
    • A21D—TREATMENT, e.g. PRESERVATION, OF FLOUR OR DOUGH, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS; PRESERVATION THEREOF
    • A21D2/00—Treatment of flour or dough by adding materials thereto before or during baking
    • A21D2/08—Treatment of flour or dough by adding materials thereto before or during baking by adding organic substances
    • A21D2/30—Organic phosphorus compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino 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
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic 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
    • A61K31/185—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
    • 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
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention belongs to the technical field of health care products, food and medicine, and particularly relates to a blood fat reducing composition and application thereof.
  • Hyperlipidemia refers to fat metabolism or abnormal operation, which makes plasma one or more lipids higher than normal. It is a systemic disease in which blood total cholesterol (TC) and/or triglyceride is too high or high-density lipoprotein cholesterol (HDL-C) is too low. Modern medicine calls it dyslipidemia, which is often called high. Lipoproteinemia. Most of the early stages of hyperlipidemia do not have any symptoms. If not corrected in time, it will gradually and systematically damage the body. It accelerates systemic atherosclerosis, which in turn causes kidney failure.
  • TC total cholesterol
  • HDL-C high-density lipoprotein cholesterol
  • hyperlipidemia can induce the following diseases: coronary heart disease, myocardial infarction, sudden cardiac death, stroke, hypertension, diabetes, fatty liver, cirrhosis, cholelithiasis, pancreatitis, hyperuricemia.
  • Amino acid is the most basic substance that constitutes a biological protein and is related to life activities. It is the basic unit that constitutes a protein molecule in a living organism and has a close relationship with the life activities of living things. It has special physiological functions in antibodies and is one of the indispensable nutrients in the body. It can exert the following effects through metabolism in the human body: 1 synthesizing tissue proteins; 2 converting into ammonia-containing substances such as acids, hormones, antibodies, creatine; 3 converting into carbohydrates and fats; 4 oxidizing into carbon dioxide and water and urea, generate energy.
  • Ornithine is a non-protein amino acid that activates the key enzymes of urea synthesis, ornithine carbamoyltransferase and carbamoyl phosphate synthase, to provide the reaction substrate ornithine, accelerate urea synthesis through the liver ornithine cycle, and promote Metabolism of ammonia to achieve detoxification of blood ammonia.
  • Aspartic acid can directly participate in the urea cycle and participate in the triphosphate cycle and the synthesis of nucleic acids in hepatocytes, which is beneficial to repair damaged liver cells.
  • B vitamins are water-soluble vitamins, including vitamin B 1 , vitamin B 2 , vitamin B 6 , vitamin B 12 , niacin, pantothenic acid, folic acid, etc., which promote metabolism in the body and convert sugar, fat, protein, etc. into heat. Missing substance. They have a synergistic effect that regulates metabolism and enhances the immune system's ability to promote cell growth and division. B 6 may be the most important of all vitamin B families. The muscles of the human body contain 70% to 80% of B 6 in the whole body. B 6 plays a key role in the metabolism of proteins, lipids and carbohydrates. Therefore, a large number of people who suffer from B 6 may have disorders including amino acid metabolism.
  • Vitamin B 6 is an important coenzyme for the metabolism and synthesis of amino acids, and participates in the physiological processes such as the metabolism of unsaturated fatty acids. It is a coenzyme of many important enzyme systems in the body and is a necessary nutrient for the normal development of animals, bacteria and yeast. In addition, vitamin B 6 is also a natural diuretic, diuretic can detoxification, intravenous vitamin B 6 5g, about 385ml of urine. Vitamin B 6 is a coenzyme of human amino acid metabolism, neurotransmitter ⁇ -aminobutyric acid (GABA) and glutamic acid (Glu). It is known that more than 60 kinds of enzymes in the liver require vitamin B 6 to participate in the promotion of normal enzyme metabolism in the body. The aspect plays a very important role, and the half-life of vitamin B 6 in the body is short and it is quickly excreted.
  • GABA neurotransmitter ⁇ -aminobutyric acid
  • Glu glutamic acid
  • liver plays an important role in the metabolic processes of lipid digestion, absorption, decomposition, synthesis and transportation. Lipid modification, synthesis, decomposition, ketone body formation, lipoprotein metabolism, etc. are all carried out in the liver.
  • the liver can secrete bile, and the bile salts in the bile can promote the digestion and absorption of lipids.
  • the triglyceride absorbed from the digestive tract is not assimilated in the liver cells and transported to the adipose tissue for storage; when starved, the stored fat is mobilized to the liver and other tissues for catabolism.
  • ⁇ -oxidation of fatty acids is particularly active, producing a large amount of acetyl-CoA (HMG-CoA) and rapidly decomposing HMG-CoA into ketone bodies.
  • HMG-CoA acetyl-CoA
  • HDL high density lipoprotein
  • LCAT lecithin cholesterol transacylase
  • fatty liver can cause hepatic fibrotic lesions, causing cirrhosis and impairing the normal function of liver cells.
  • the principle of fatty liver is mainly due to excessive fat and fatty acid input into the liver and dysfunction of plasma lipoprotein in the liver.
  • the hypolipidemic composition is a combination of a compound amino acid and a vitamin designed for patients with hyperlipidemia diseases, which can effectively lower the blood lipid concentration and awaken the patient's body's ability to lower blood fat.
  • Still another object of the present invention is to provide the use of the above hypolipidemic composition.
  • composition contains ornithine, aspartic acid and vitamin B 6.
  • composition also contains one or more of the following auxiliary ingredients: vitamin C, citric acid, pantothenic acid, biotin, folic acid.
  • the amount of auxiliary ingredients is determined by weight ratio:
  • the dosage form when the composition is a health care product or a medicine is any one of pharmaceutically acceptable dosage forms, and the preferred dosage forms are: granules, tablets, capsules, powders, pills, powders, wines, ointments, and remedies. , granules, membranes, oral liquids, injections.
  • composition in the preparation of a hypolipidemic health care product, a pharmaceutical, a food or a food additive.
  • the food additive may be added to various types of foods, for example, as an additive for baking cakes, beverages, butter dairy products, and the like.
  • Characterized aspect of the present invention is utilization ornithine, aspartic acid and vitamin B 6 and other substances, when ornithine, aspartic acid and vitamin B 6 in combination, ornithine as a reaction of the urea cycle
  • the substrate rapidly activates the urea cycle in the liver cells, so that the enzyme metabolism in the liver is gradually restored, thereby restoring the vitality of the liver and protecting the liver and protecting the liver.
  • Aspartic acid can directly participate in the urea cycle and participate in the triphosphate cycle and the synthesis of nucleic acids in hepatocytes, which is beneficial to repair damaged liver cells.
  • Vitamin B 6 is an important coenzyme for the metabolism and synthesis of amino acids, and participates in physiological processes such as metabolism of unsaturated fatty acids. It is a coenzyme of many important enzyme systems in the body and is a necessary nutrient for normal animal development, bacterial and yeast reproduction. And vitamin B 6 is also a natural diuretic, diuretic can detoxification.
  • the combination of ornithine, aspartic acid and vitamin B 6 can effectively repair damaged liver cells, restore liver function, and awaken the body's ability to lower blood fat.
  • the combination of the three produces phosphatidylcholine to aid in the emulsification of fat; the liver also promotes the synthesis of bile salts and digests large amounts of triglycerides.
  • the liver is not only a group of essential organs for the synthesis of cholesterol in the body, but also the cholesterol transported from the high-density lipoprotein into the liver is also transformed and excreted in the liver cells. A part of cholesterol is directly used as a bile component along with the bile salt through the biliary tract. At this time, the metabolic waste can be smoothly discharged from the body under the action of vitamin B 6 .
  • the composition prepared by the invention not only has small side effects, the disease is not easy to relapse, the treatment period is short, and The patient provides nutritional support, effectively restores the body's own hypolipidemic function, promotes enzyme metabolism, and achieves the goal of treating the symptoms.
  • the components used in the composition of the invention can be derived from food, have high safety, and have no toxic and side effects for long-term consumption, but the content ratio of each component is inconsistent with that in the food, and experimentally found that the composition can play general food. It does not have a lipid-lowering effect.
  • Example 1 Making a high-fat sandwich biscuit as a food additive
  • the production process is as follows:
  • the wheat flour, eggs, sweeteners, baking soda, vegetable oil, and water are prepared into dough by weight ratio, and placed in a refrigerator for 1 hour, and then taken out into 2 to 3 mm sheets, and pressed out with a biscuit grinder, one Hollow, a solid, made of biscuit ectoderm.
  • a blood-lowering health oral liquid is weighed and weighed according to the following weight: L-ornithine 20g, L-aspartic acid 5g, vitamin B 6 25g, vitamin C 15g, xylitol 5g, water 20ml, Mix well, and the mixture can be sealed in a 5-50 mL bottle, sterilized at 110 ° C for 20 min.
  • a pharmaceutical composition capsule preparation which comprises a component of L-ornithine 70g, L-aspartic acid 60g, vitamin B 6 70g, 1% polyvinylpyrrolidone ethanol solution, 2g magnesium stearate, and a total of 800 capsules.
  • Preparation method weigh L-ornithine, L-aspartic acid, vitamin B 6 and mix well. Make soft material with 40% of 1% polyvinylpyrrolidone ethanol solution, granulate with 20 mesh sieve, dry until moisture More than 3%, and adding 2g of magnesium stearate, mixing, passing through 20 mesh sieve, granules, subpacking, polishing, packaging, after the above process, capsule preparation.
  • a pharmaceutical composition tablet having a composition of 70 g of L-ornithine, 60 g of L-aspartic acid, 70 g of vitamin B 6 , 1% of a solution of polyvinylpyrrolidone in ethanol, and 1 g of magnesium stearate. 1000 pieces.
  • Preparation method weigh L-ornithine, L-aspartic acid, vitamin B 6 and mix well, and make soft material with 20% of 1% polyvinylpyrrolidone ethanol solution, then granulate with 20 mesh sieve, dry, and Add 1g of magnesium stearate to mix, sift through 20 mesh, compress, compress and package. After the above steps, the composition tablets are obtained.
  • a pharmaceutical composition comprising 250 mL of a mixed injection comprising: L-ornithine 6 g, L-aspartic acid 4 g, vitamin B 6 6 g, vitamin C 3.5 g, biotin 0.1 mg added to 250 mL 5 % glucose sodium chloride injection (diabetes patients use 0.9% sodium chloride injection).
  • a pharmaceutical composition granule having a composition of 70 g of L-ornithine, 60 g of L-aspartic acid, 70 g of vitamin B 6 , 0.5 g of citric acid, 5 mg of pantothenic acid, 0.2 mg of biotin, and folic acid 0.3 Mg, vitamin C 15g.
  • a suitable amount of a 20% ethanol solution is a humectant to prepare a granule.
  • Preparation method Weigh the above components, mix well, add 40ml of 20% ethanol solution to make soft material, granules by extrusion spheronization method, and dry until the moisture does not exceed 3%.
  • a pharmaceutical composition granule having a composition of 70 g of L-ornithine, 60 g of D-aspartic acid, 70 g of vitamin B 6 , 0.5 g of citric acid, 0.2 mg of biotin, and 20 g of vitamin C.
  • a suitable amount of a 20% ethanol solution is a humectant to prepare a granule.
  • Preparation method Weigh the above components, mix well, add 40ml of 20% ethanol solution to make soft material, granules by extrusion spheronization method, and dry until the moisture does not exceed 3%.
  • a pharmaceutical composition granule having a composition of 70 g of DL-ornithine, 50 g of L-aspartic acid, 60 g of vitamin B 6 , 30 mg of pantothenic acid, 0.5 mg of biotin, and 20 g of vitamin C.
  • a suitable amount of a 20% ethanol solution is a humectant to prepare a granule.
  • Preparation method Weigh the above components, mix well, add 40ml of 20% ethanol solution to make soft material, granules by extrusion spheronization method, and dry until the moisture does not exceed 3%.
  • a pharmaceutical composition granule having a composition of 70 g of L-ornithine, 50 g of DL-aspartic acid, 60 g of vitamin B 6 , 30 mg of pantothenic acid, 3 mg of folic acid, and 5 g of vitamin C.
  • a suitable amount of a 20% ethanol solution is a humectant to prepare a granule.
  • Preparation method Weigh the above components, mix well, add 40ml of 20% ethanol solution to make soft material, granules by extrusion spheronization method, and dry until the moisture does not exceed 3%.
  • a pharmaceutical composition granule having a composition of 70 g of L-ornithine, 50 g of DL-aspartic acid, 35 g of vitamin B 6 and 45 g of vitamin C.
  • a suitable amount of a 20% ethanol solution is a humectant to prepare a granule.
  • Preparation method Weigh the above components, mix well, add 40ml of 20% ethanol solution to make soft material, granules by extrusion spheronization method, and dry until the moisture does not exceed 3%.
  • Example 11 Antihyperlipidemic animal experiment of the composition of the invention
  • Experimental materials 150 healthy SD clean grade rats, weighing (150.2 ⁇ 8.9) g both male and female.
  • feed ordinary feed
  • high-fat feed formula basic feed 72.7%, cholesterol 2%, egg yolk powder 5%, lard 10%, propyl thiouracil 0.2%, sucrose 10%, sodium cholate 0.1%.
  • Animal grouping and drug administration The purchased experimental rats were adapted to feed for 1 week in the laboratory, and the original number was compiled according to the weighing order.
  • the random number table was randomly divided into blank control group, model control group and pharmaceutical composition (respectively Prepared in Examples 3, 6, 8, and 10, dissolved in 50 ml of 10 g of water, formulated into a solution) low dose group (5 ml/kg ⁇ d), medium dose group (10 ml/kg ⁇ d), high dose group (15 ml/kg) d), a positive drug (simvastatin) control group (1.5 mg/kg, volume 10 ml/kg), 10 rats in each group.
  • the blank control group and the model control group were intragastrically administered with normal saline (volume 10 ml/kg).
  • the drug-administered group was intragastrically administered with the corresponding drug once a day, and the body weight was weighed once a week.
  • the blank control group was fed with normal diet, and the other groups were fed with high-fat diet. During the test period, they were given free access to food, free access to water, continuous modeling and prevention for 4 weeks.
  • Rats were anesthetized with 3% pentobarbital sodium, blood was taken from the abdominal aorta, serum was separated, and serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipid were measured.
  • TC serum total cholesterol
  • TG triglyceride
  • HDL-C high-density lipoprotein cholesterol
  • LDL-C Protein cholesterol
  • ALT aspartate aminotransferase
  • the levels of TC, TG and LDL-C in the serum of the model group were significantly higher than those in the normal group (P ⁇ 0.05), showing a typical disorder of lipid metabolism, indicating that the experimental hyperlipidemia model replicated. success.
  • the treatment group can significantly reduce serum TC, TG, LDL-C content (P ⁇ 0.05), and can significantly increase serum HDL-C content (P ⁇ 0.01) in a dose-dependent manner.
  • Serum ALT and AST can reflect liver function. ALT and AST in the high-fat diet group were significantly higher than those in the basal diet group (P ⁇ 0.01), indicating that the liver had some damage. The serum ALT and AST levels of each drug-administered group were lower than the model control group, and the middle-dose and high-dose groups were significantly different from the model control group (P ⁇ 0.01), indicating that the composition of the present invention protects liver function. It has a significant effect and has obvious protective effect on the body.
  • the composition of the present invention promotes fatty acid metabolism, improves intrahepatic lipid metabolism, protects liver cells, has certain lipid-lowering and liver-protecting effects, and is especially suitable for hyperlipidemia patients with high risk of impaired liver function.
  • Pharmacological experiments prove that the ornithine, aspartic acid and vitamin B6 in the present invention have a synergistic effect and can enhance the mutual effect.
  • Example 12 The role of the composition of the invention in clinical treatment
  • TC serum total cholesterol
  • TG triglyceride
  • TC serum total cholesterol
  • TG triglyceride
  • LDL-C low-density lipoprotein Cholesterol
  • HDL-C high-density lipoprotein
  • composition of the invention (prepared as in Example 3) was then started, two capsules each time, three times a day, each containing about 0.25 g of the composition of the invention, for four weeks, during which no spicy spicy food, especially alcohol, was consumed.
  • the blood lipid test after treatment reaches any of the following, that is, the TC decreases by ⁇ 20%, or the TG decreases ⁇ 40%, or HDL-C rise ⁇ 0.26mmol / L, or HDL-C / LDL-C decreased ⁇ 20%, or LDL-C decreased ⁇ 30%.
  • the blood lipid test after treatment reaches any of the following, that is, the TC decreases by ⁇ 10% but ⁇ 20%, or the TG decreases by ⁇ 20% but ⁇ 40%, or the HDL-C rises ⁇ 0.14mmol/L but ⁇ 0.26mmol/ L, or HDL-C/LDL-C decreased by ⁇ 10% but ⁇ 20%, or LDL-C decreased by ⁇ 20%.

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Abstract

一种含有鸟氨酸、门冬氨酸、维生素B6的组合物，及其在制备降血脂的药物、保健品、食品或者食品添加剂中的用途。

Description

一种降血脂组合物及其应用 技术领域
本发明属于保健品、食品及医药技术领域，具体涉及一种降血脂组合物及其应用。
背景技术
高脂血症是指脂肪代谢或运转异常使血浆一种或多种脂质高于正常。它是一种全身性疾病，血总胆固醇(TC)和(或)甘油三酯过高或高密度脂蛋白胆固醇(HDL-C)过低，现代医学称之为血脂异常，也常称为高脂蛋白血症。高脂血症初期多数没有任何症状，若没有及时的纠正，会对身体产生逐渐进行性的全身性的损害。它会加速全身动脉粥样硬化，继而引起肾功能衰竭。目前资料研究表明，高血脂症能使人诱发以下疾病：冠心病、心肌梗死、心脏猝死、脑卒中、高血压、糖尿病、脂肪肝、肝硬化、胆石症、胰腺炎、高尿酸血症等。
氨基酸是构成生物体蛋白质并同生命活动有关的最基本的物质，是在生物体内构成蛋白质分子的基本单位，与生物的生命活动有着密切的关系。它在抗体内具有特殊的生理功能，是生物体内不可缺少的营养成分之一。其在人体内通过代谢可以发挥下列一些作用：①合成组织蛋白质；②变成酸、激素、抗体、肌酸等含氨物质；③转变为碳水化合物和脂肪；④氧化成二氧化碳和水及尿素，产生能量。鸟氨酸是非蛋白氨基酸，能激活尿素合成的关键酶-鸟氨酸氨基甲酰转移酶和氨基甲酰磷酸合成酶，提供反应底物鸟氨酸，通过肝脏鸟氨酸循环加速尿素合成，促进氨的代谢，从而达到对血氨的解毒作用。门冬氨酸首先能直接参与尿素循环并参与三磷酸循环及肝细胞内核酸的合成，有利于修复被损伤的肝细胞。此外，由于门冬氨酸对肝细胞内三羧酸循环代谢过程的间接促进作用，并提供能量代谢的中间产物，促进了肝细胞的能量生成，使被损伤的肝细胞的各项功能得以迅速恢复。
B族维生素是水溶性维生素，包括维生素B1、维生素B2、维生素B6、维生素B12、烟酸、泛酸、叶酸等，是推动体内代谢，把糖、脂肪、蛋白质等转化成热量时不可缺少的物质。它们具有协同作用，调节新陈代谢，增进免疫系统促进细胞生长和分裂。B6 可能是所有维生素B族中最重要的一种。人体的肌肉里含有全身70％～80％的B6。B6在蛋白、脂质和碳水化合物的代谢中发挥着关键的作用。所以，大量损耗B6的人会出现包括氨基酸代谢紊乱。维生素B6是氨基酸的代谢与合成的重要辅酶，并参与不饱和脂肪酸的代谢等生理过程，是机体内许多重要酶系统的辅酶，是动物正常发育、细菌和酵母繁殖所必需的营养成分。另外，维生素B6还是一种天然的利尿剂，利尿就能解毒，静脉输入维生素B65g，大约能利出尿液380ml左右。维生素B6是人体氨基酸代谢、神经递质γ-氨基丁酸(GABA)和谷氨酸(Glu)的辅酶，现已知肝脏有60多种酶需要维生素B6参与，在促进机体正常酶代谢方面起到十分重要的作用，且维生素B6在体内的半衰期短，很快就排出体外。
众所周知，肝脏在脂类的消化、吸收、分解、合成和运输等代谢过程中均起很重要的作用。脂类的改造、合成、分解、酮体生成、脂蛋白代谢等等都在肝脏中进行。肝脏能分泌胆汁，胆汁中的胆汁酸盐能促进脂类的消化和吸收。从消化道吸收的甘油三脂在肝细胞没进行同化，运至脂肪组织内储存；饥饿时，储存的脂肪被动员到肝脏及其他组织进行分解代谢。在肝脏内，脂肪酸的β-氧化特别活跃，产生大量的乙酰辅酶A(HMG-CoA)，并将HMG-CoA迅速分解为酮体。并且脂类的运输及其转化均与肝脏功能有着密切关系。如血浆中的极低密度脂蛋白(VLDL)，主要在肝脏内合成，它在血浆中转化为低密度脂蛋白(LDL)，并释放出部分高密度脂蛋白(HDL)，而催化这些转变的一个重要酶-卵磷脂胆固醇转酰酶(LCAT)，也是在肝细胞内合成的。如果以上的代谢反应受到阻碍，肝中脂类的含量就会发生变动，当脂肪在肝中过量存积就会引发脂肪肝。慢性的脂肪肝会引起肝细胞纤维性病变，造成肝硬化，损害肝细胞的正常功能。脂肪肝的发生原理主要是由于输入肝脏的脂肪和脂肪酸过多及肝脏中血浆脂蛋白的合成代谢障碍。
现在社会，随着人们生活水平的提高以及饮食结构的改变，高脂血症患病率在全世界范围内呈不断上升的趋势。至今针对高血脂症治疗的药物有许多，多数是化学合成的化学药品或由某些中药组成的中药复方。化学合成药因其制作工艺，其中存在少量有害物质，长期使用会出现毒性，且后期效果不是很理想；中药复方制剂，因其药效缓和，用药时间长。因此开发出新型的、有效的降血脂的药物或保健产品减低血脂浓度对人体的健康危害是非常有必要的。
发明内容
本发明的目的是针对上述技术问题提供一种降血脂组合物。该降血脂组合物是为高血脂症疾病患者设计的一种复方氨基酸和维生素的组合物，能有效降低血脂浓度，唤醒患者机体本身降血脂能力。
本发明还有一个目的是提供上述降血脂组合物的应用。
本发明的目的是通过下列技术方案实现的：
一种降血脂组合物，该组合物含有鸟氨酸、门冬氨酸和维生素B6。
所述的组合物含有下列重量比的组分：鸟氨酸：门冬氨酸：VB6＝1：0.1～1.2：0.2～1.5，优选鸟氨酸：门冬氨酸：VB6＝1：0.3～0.7：0.4～0.8，进一步优选鸟氨酸：门冬氨酸：VB6＝1：0.5：0.6。
所述的组合物还含有以下辅助成分中的一种或几种：维生素C、枸橼酸、泛酸、生物素、叶酸。
其中辅助成分的用量按重量比计分别为：
鸟氨酸：VC＝1：0.05～1.2，优选鸟氨酸：VC＝1：0.2～0.8，进一步优选鸟氨酸：VC＝1：0.5；
鸟氨酸：枸橼酸＝1：0.001～0.05，优选鸟氨酸：枸橼酸＝1：0.001～0.03，进一步优选鸟氨酸：枸橼酸＝1：0.01；
鸟氨酸：泛酸＝1：0.00001～0.001，优选鸟氨酸：泛酸＝1：0.00005～0.0008，进一步优选鸟氨酸：泛酸＝1：0.0005；
鸟氨酸：生物素＝1：0.000001～0.0005，优选鸟氨酸：生物素＝1：0.000001～0.0001，进一步优选鸟氨酸：生物素＝1：0.000003；
鸟氨酸：叶酸＝1：0.000001～0.0005，优选鸟氨酸：叶酸＝1：0.000003～0.0001，进一步优选鸟氨酸：叶酸＝1：0.00005。
所述的组合物，其中鸟氨酸是指L-鸟氨酸、D-鸟氨酸或者DL-鸟氨酸；门冬氨酸是指L-门冬氨酸、D-门冬氨酸或者DL-门冬氨酸。
所述组合物为保健品或药物时的剂型为药剂学上允许的任何一种剂型，优选的剂型为：颗粒剂、片剂、胶囊剂、散剂、丸剂、粉剂、酒剂、膏剂、丹剂、冲剂、膜剂、口服液、注射剂。
所述组合物在制备降血脂的保健品、药物、食品或食品添加剂中的应用。
所述的食品添加剂，可以添加应用于各类食品中，例如可以作为烘烤糕点、饮料、黄油奶制品等的添加剂。
本发明技术方案综合利用鸟氨酸、门冬氨酸和维生素B6等物质的作用特点，当鸟氨酸、门冬氨酸和维生素B6的联合使用时，鸟氨酸作为尿素循环的反应底物，迅速激活肝细胞内的尿素循环，使得肝脏内酶代谢逐步恢复，从而使得肝脏的活力得到恢复，起到保肝、护肝的作用。门冬氨酸首先能直接参与尿素循环并参与三磷酸循环及肝细胞内核酸的合成，有利于修复被损伤的肝细胞。此外，门冬氨酸对肝细胞内三羧酸循环代谢过程起着间接促进作用，并提供能量代谢的中间产物，促进了肝细胞的能量生成，使被损伤的肝细胞的各项功能得以迅速恢复。而维生素B6是氨基酸的代谢与合成的重要辅酶，并参与不饱和脂肪酸的代谢等生理过程，是机体内许多重要酶系统的辅酶，是动物正常发育、细菌和酵母繁殖所必需的营养成分。且维生素B6还是一种天然的利尿剂，利尿就能解毒。所以鸟氨酸、门冬氨酸和维生素B6的联合使用，能有效的修复受损的肝细胞，恢复肝功能，唤醒机体本身降血脂能力。三者联合使用产生磷脂酰胆碱，帮助脂肪的乳化；肝脏还能促进胆汁盐的合成，消化大量的甘油三脂。而肝脏不仅是体内合成胆固醇的组要器官，并且由高密度脂蛋白转运入肝的胆固醇也在肝细胞转化和排出。一部分胆固醇直接作为胆汁成分与胆汁盐一起经胆道入肠，此时，还能在维生素B6的作用下，顺利将代谢废弃物排出体外。
本发明组合物的优点在于：
对治疗高脂血症有显著的疗效，与现有的化学合成药和中药复方降血脂的方法比较，本发明所制成的组合物不仅副作用小、疾病不易复发、治疗周期短，而且能为患者提供营养支持、有效的恢复机体本身的降血脂功能、促进酶代谢，达到治标治本的目的。
本发明组合物采用的组分均可来源于食物，安全性高，长期食用无毒副作用，但其各组分的含量比例与食物中的不一致，经实验研究发现，该组合物可发挥一般食物所不具有的降脂作用。
具体实施方式
以下根据实施例进一步具体说明本发明，但本发明不限于以下实施例。
实施例1：作为食品添加剂制作降高血脂夹心饼干
制作工艺如下：
1、将小麦粉、鸡蛋、甜味剂、小苏打、植物油、水按重量配比调制成面团，并放冰箱冷藏松弛1小时后取出擀成2～3mm薄片，用饼干磨具压出形状，一个空心，一个实心，制成饼干外胚。
2、放入烤箱烘烤，冷却，备用。
3、称取适量果酱，以果酱及L-鸟氨酸、L-门冬氨酸及维生素B6的量为总重量100份，按以下重量份数的原料混合均匀：3份L-鸟氨酸、2份L-门冬氨酸、3份维生素B6及92份果酱，制成食品添加剂，抹入饼干空心部位即可。
实施例2：保健口服液制备例
一种降高血脂保健口服液，按下述重量称取各原料：L-鸟氨酸20g、L-门冬氨酸5g、维生素B625g、维生素C 15g、木糖醇5g、水20ml，混合均匀，并将混合物罐装到5～50mL瓶中密封，110℃、灭菌20min。
实施例3：药物组合物制备例
一种药物组合物胶囊制剂，其组分为L-鸟氨酸70g，L-门冬氨酸60g，维生素B670g，1％聚乙烯吡咯烷酮乙醇溶液适量，2g硬脂酸镁，共制成800粒。
制备方法：称取L-鸟氨酸、L-门冬氨酸、维生素B6，混合均匀，用1％聚乙烯吡咯烷酮乙醇溶液40mL制成软材，用20目筛制粒，干燥至水分不超过3％，并加入2g硬脂酸镁，混匀，过20目筛整粒，分装，抛光，包装，经过以上工序即得胶囊制剂。
实施例4：药物组合物制备例
一种药物组合物片剂，其组分为L-鸟氨酸70g，L-门冬氨酸60g，维生素B670g，1％聚乙烯吡咯烷酮乙醇溶液适量，1g硬脂酸镁，共制成1000片。
制备方法：称取L-鸟氨酸、L-门冬氨酸、维生素B6，混合均匀，用1％聚乙烯吡咯烷酮乙醇溶液20mL制成软材，接着用20目筛制粒，干燥，并加入1g硬脂酸镁混匀，过20目筛整粒，压片，抛光，包装，经过以上工序即得组合物片剂。
实施例5：药物组合物制备例
一种药物组合物，其组分为混合物质注射液250mL含有：L-鸟氨酸6g，L-门冬氨酸4g，维生素B66g，维生素C 3.5g，生物素0.1mg加入到250mL 5％葡萄糖氯化钠注射液(糖尿病患者采用0.9％氯化钠注射液)中。
实施例6：
一种药物组合物颗粒剂，其组分为L-鸟氨酸为70g，L-门冬氨酸为60g，维生素B670g，枸橼酸0.5g，泛酸5mg，生物素0.2mg，叶酸0.3mg，维生素C 15g。20％乙醇溶液适量为湿润剂，制成颗粒剂。
制备方法：称取上述组分，混合均匀，加入20％乙醇溶液40ml制成软材，挤出滚圆法制成颗粒，干燥至水分不超过3％，即可。
实施例7：
一种药物组合物颗粒剂，其组分为L-鸟氨酸为70g，D-门冬氨酸为60g，维生素B670g，枸橼酸0.5g，生物素0.2mg，维生素C 20g。20％乙醇溶液适量为湿润剂，制成颗粒剂。
制备方法：称取上述组分，混合均匀，加入20％乙醇溶液40ml制成软材，挤出滚圆法制成颗粒，干燥至水分不超过3％，即可。
实施例8：
一种药物组合物颗粒剂，其组分为DL-鸟氨酸为70g，L-门冬氨酸为50g，维生素B660g，泛酸30mg，生物素0.5mg，维生素C 20g。20％乙醇溶液适量为湿润剂，制成颗粒剂。
制备方法：称取上述组分，混合均匀，加入20％乙醇溶液40ml制成软材，挤出滚圆法制成颗粒，干燥至水分不超过3％，即可。
实施例9：
一种药物组合物颗粒剂，其组分为L-鸟氨酸为70g，DL-门冬氨酸为50g，维生素B660g，泛酸30mg，叶酸3mg，维生素C 5g。20％乙醇溶液适量为湿润剂，制成颗粒剂。
制备方法：称取上述组分，混合均匀，加入20％乙醇溶液40ml制成软材，挤出滚圆法制成颗粒，干燥至水分不超过3％，即可。
实施例10：
一种药物组合物颗粒剂，其组分为L-鸟氨酸为70g，DL-门冬氨酸为50g，维生素B635g，维生素C 45g。20％乙醇溶液适量为湿润剂，制成颗粒剂。
制备方法：称取上述组分，混合均匀，加入20％乙醇溶液40ml制成软材，挤出滚圆法制成颗粒，干燥至水分不超过3％，即可。
实施例11：本发明组合物的降血脂动物实验
1、实验材料：健康SD清洁级大鼠150只，体重(150.2±8.9)g雌雄兼用。
2、饲料：普通饲料，高脂饲料配方为：基础饲料72.7％、胆固醇2％、蛋黄粉5％、猪油10％、丙硫氧嘧啶0.2％、蔗糖10％、胆酸钠0.1％。
3、动物分组与给药：购入的实验大鼠在实验室适应饲养1周，按称重顺序编原始号，查随机数字表随机分成空白对照组、模型对照组、药物组合物(分别按实施例3、6、8、10制备，每10g加水50ml溶解，配成溶液)低剂量组(5ml/kg·d)，中剂量组(10ml/kg·d)，高剂量组(15ml/kg·d)，阳性药物(辛伐他汀)对照组(1.5mg/kg，容积为10ml/kg)，每组10只。从实验之日起空白对照组、模型对照组灌胃生理盐水(容积为10ml/kg)，给药组灌胃相应药物，1次/d，每周称1次体重，根据体重调整给药量。空白对照组喂饲普通饲料，其余各组喂饲高脂饲料，试验期间自由摄食、自由饮水，连续造模并预防给药4周。
4、观测指标：末次给药后禁食12h，不禁水。3％戊巴比妥钠麻醉大鼠，腹主动脉取血，离心分离血清，测血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)值。
5、结果
a)本发明组合物对大鼠血脂水平的影响
由表1可见，与正常组相比，模型组大鼠血清中TC、TG、LDL-C的水平明显升高(P＜0.05)，呈现典型的脂质代谢紊乱，表明实验性高血脂模型复制成功。与模型组相比，治疗组能明显降低血清TC、TG、LDL-C含量(P＜0.05)，并能显著升高血清HDL-C含量(P＜0.01)且呈现剂量依赖性。
表1 各组大鼠血脂变化(
Figure PCTCN2015083178-appb-000001
n＝10)
Figure PCTCN2015083178-appb-000002
Figure PCTCN2015083178-appb-000003
b)本发明组合物对大鼠肝功能的影响
血清中ALT和AST可以反应肝脏功能。高脂饲料组ALT和AST明显高于基础饲料组(P<0.01)，说明肝脏有一定损害。而各给药组的血清ALT和AST水平均低于模型对照组，且中剂量、高剂量组与模型对照组比较差异及其显著(P<0.01)，说明本发明组合物在保护肝脏功能方面有显著效果，且对机体有明显的保护作用。
表2 各组大鼠肝功能变化情况(
Figure PCTCN2015083178-appb-000004
n＝10)
Figure PCTCN2015083178-appb-000005
Figure PCTCN2015083178-appb-000006
高脂血症大鼠灌服本发明组合物后，其TC、TG、LDL-C含量明显降低，而HDL-C含量升高；对高脂饲料造成的血清中ALT和AST的增高有抑制作用。说明本发明组合物促进了脂肪酸代谢，改善肝内脂质代谢，保护肝细胞，有一定的调脂护肝作用，尤其适用于肝功能受损危险度较高的高血脂患者。药理实验证明，本发明中鸟氨酸、门冬氨酸、维生素B6，具有协同作用，可相互增强疗效。
实施例12：本发明组合物在临床治疗中的作用
1、病例选择
将血清总胆固醇(TC)＞5.7mmol/L及(或)甘油三脂(TG)＞1.7mmol/L者选为观察对象，共24例。其中男14例，女10例，年龄26～69岁。
2、诊断标准
参照2010年人民卫生出版社出版的《内科学》，其中有关高血脂的诊断标准，血清总胆固醇(TC)≥5.72mmol/L，甘油三脂(TG)≥1.70mmol/L，低密度脂蛋白胆固醇(LDL-C)≥3.10mmol/L，高密度脂蛋白(HDL-C)男性≤1.04mmol/L，女性≤1.17mmol/L。
3、治疗方法
所有患者在抽血前一天的晚餐禁止饮酒以及近视过量的脂质食品，空腹12小时以上取静脉血，测TC、TG、HDL-C、LDL-C。然后开始服用本发明组合物(按实施例3制备)，每次2粒，每日三次，每粒约含本发明组合物0.25g，连服四周，治疗期间忌食辛辣刺激食物尤其是饮酒。
4、疗效评定标准
显效：治疗后血脂检测达到以下任何一项者，即TC下降≥20％，或者TG下降≥ 40％，或HDL-C上升≥0.26mmol/L，或HDL-C/LDL-C下降≥20％，或LDL-C下降≥30％。
有效：治疗后血脂检测达到以下任何一项者，即TC下降≥10％但＜20％，或TG下降≥20％但＜40％，或HDL-C上升≥0.14mmol/L但＜0.26mmol/L，或HDL-C/LDL-C下降≥10％但＜20％，或LDL-C下降≥20％。
无效：治疗前后血脂检测物明显改善或改善达不到标准者。
5、治疗效果
24例患者经过两周本发明组合物治疗后，其中显效8例，有效11例，无效5例，无效5例中TC、TG都有不同程度的下降。继续服用本发明组合物两周后，其中显效达到14例，有效9例，无效1例，无效率4.2％，总有效率95.8％。
6、具体病例介绍
(1)高某，男，33岁，高脂血症。治疗前总胆固醇(TC)为6.31mmol/L，甘油三脂(TG)为2.16mmol/L。服用本发明组合物后两周，总胆固醇(TC)降为4.92mmol/L，甘油三脂(TG)降为0.99mmol/L。
(2)徐某，女，69岁，高脂血症。治疗前总胆固醇(TC)为5.79mmol/L，甘油三脂(TG)为4.12mmol/L。服用本发明组合物后两周，总胆固醇(TC)降为5.46mmol/L，甘油三脂(TG)降为1.50mmol/L。

Claims (7)

  1. 一种降血脂组合物，其特征在于，所述组合物含有鸟氨酸、门冬氨酸和维生素B6。
  2. 根据权利要求1所述的组合物，其特征在于所述组合物含有下列重量比的组分：鸟氨酸：门冬氨酸：VB6＝1：0.1～1.2：0.2～1.5，优选鸟氨酸：门冬氨酸：VB6＝1：0.3～0.7：0.4～0.8，进一步优选鸟氨酸：门冬氨酸：VB6＝1：0.5：0.6。
  3. 根据权利要求1所述的组合物，其特征在于所述组合物还含有以下辅助成分中的一种或几种：维生素C、枸橼酸、泛酸、生物素、叶酸。
  4. 根据权利要求3所述的组合物，其特征在于辅助成分的用量按重量比计分别为：
    鸟氨酸：VC＝1：0.05～1.2，优选鸟氨酸：VC＝1：0.2～0.8，进一步优选鸟氨酸：VC＝1：0.5；
    鸟氨酸：枸橼酸＝1：0.001～0.05，优选鸟氨酸：枸橼酸＝1：0.001～0.03，进一步优选鸟氨酸：枸橼酸＝1：0.01；
    鸟氨酸：泛酸＝1：0.00001～0.001，优选鸟氨酸：泛酸＝1：0.00005～0.0008，进一步优选鸟氨酸：泛酸＝1：0.0005；
    鸟氨酸：生物素＝1：0.000001～0.0005，优选鸟氨酸：生物素＝1：0.000001～0.0001，进一步优选鸟氨酸：生物素＝1：0.000003；
    鸟氨酸：叶酸＝1：0.000001～0.0005，优选鸟氨酸：叶酸＝1：0.000003～0.0001，进一步优选鸟氨酸：叶酸＝1：0.00005。
  5. 根据权利要求1-4任一所述的组合物，其特征在于鸟氨酸是指L-鸟氨酸、D-鸟氨酸或者DL-鸟氨酸；门冬氨酸是指L-门冬氨酸、D-门冬氨酸或者DL-门冬氨酸。
  6. 权利要求1～4所述的任一组合物，其特征在于该组合物为保健品或药物时的剂型为药剂学上允许的任何一种剂型，优选的剂型为：颗粒剂、片剂、胶囊剂、散剂、丸剂、粉剂、酒剂、膏剂、丹剂、冲剂、膜剂、口服液、注射剂。
  7. 权利要求1～4所述的任一组合物在制备降血脂的保健品、药物、食品或食品添加剂中的应用。
PCT/CN2015/083178 2014-07-03 2015-07-02 一种降血脂组合物及其应用 WO2016000637A1 (zh)

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