WO2011160259A1 - Use of n-carbamoyl glutamic acid, salts or esters thereof in manufacture of health care products for protecting liver or promoting muscle growth - Google Patents

Use of n-carbamoyl glutamic acid, salts or esters thereof in manufacture of health care products for protecting liver or promoting muscle growth Download PDF

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WO2011160259A1
WO2011160259A1 PCT/CN2010/000944 CN2010000944W WO2011160259A1 WO 2011160259 A1 WO2011160259 A1 WO 2011160259A1 CN 2010000944 W CN2010000944 W CN 2010000944W WO 2011160259 A1 WO2011160259 A1 WO 2011160259A1
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salt
acid
amino acid
liver
ester
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PCT/CN2010/000944
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French (fr)
Chinese (zh)
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胡长春
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上海永颐生物科技有限公司
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Publication of WO2011160259A1 publication Critical patent/WO2011160259A1/en

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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
    • 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
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/315—Zinc compounds
    • 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
    • A61K31/435—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
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • N-carbamoylglutamic acid its salt or ester thereof in preparing liver protection and muscle growth promoting health care products
  • the invention belongs to the technical field of health care products, and particularly relates to the application of N-carbamoylglutamic acid, a salt thereof or an ester thereof for preparing a liver-protecting and muscle-promoting health care product. Background technique
  • Arginine has an important nutritional role in mammals. Arginine deficiency has been considered as a limiting factor for growth.
  • Carbamoyl phosphate synthase-1 (CPS-1) is the rate-limiting enzyme for endogenous synthesis of arginine. , plays a big role in the conversion of ornithine and citrulline to arginine.
  • N-acetylglutamate (NAG) is known to act as an activator of CPS-1, which activates CPS-1, thereby increasing the endogenous synthesis of arginine.
  • NAG in the body depends mainly on two factors: First, the synthesis of NAG in vivo requires NAG synthase, which lacks sufficient NAG supply in the body; in addition, mammalian cytosol contains highly active deacyl Enzyme, which decomposes NAG, thereby reducing the amount of NAG in the body, which in turn affects the endogenous synthesis of arginine.
  • N-carbamoylglutamic acid is a structural analog of NAG
  • Chinese Patent Application Publication No. CN101481336 provides a method for preparing N-carbamoylglutamic acid by reacting glutamic acid with urea.
  • An object of the present invention is to provide an application of N-carbamoylglutamic acid, a salt thereof or an ester thereof for the preparation of a liver-protecting and muscle-promoting growth health product.
  • the N-carbamoylglutamic acid is L-form;
  • the salt of the N-carbamoylglutamic acid is a mineral acid salt, an organic acid salt, a metal salt, an ammonium salt, an organic ammonium salt or an amino acid salt
  • the ester of N-carbamoylglutamic acid is a lower alcohol ester, preferably a methyl or ethyl ester.
  • the amino acid composition having liver protection and muscle growth promoting effect provided by the present invention comprises, by weight percent, the following components:
  • the zinc-containing compound is zinc acetate dihydrate or zinc citrate
  • the salt of N-carbamoylglutamic acid or the salt of arginine is a mineral acid salt, an organic acid salt, a metal salt, an ammonium salt, an organic ammonium salt or an amino acid salt; the N-carbamoyl glutamic acid
  • the ester, ester of arginine is a lower alcohol ester, preferably a methyl or ethyl ester.
  • the above inorganic acid salt may be a hydrochloride, a sulfate, a nitrate, a phosphate or the like.
  • the organic acid salt may be acetate, maleate, fumarate, citrate, malate-lactate, alpha-ketoglutarate, gluconic acid, octanoate or the like.
  • the metal salt may be an alkali metal salt such as a sodium salt or a potassium salt, an alkaline earth metal salt such as a magnesium salt or a calcium salt, an aluminum salt or a zinc salt.
  • the organic ammonium salt may be a morpholine salt or a piperidine salt or the like.
  • the amino acid salt can be a glycinate, a phenylalanine salt, a lysine salt or an aspartate salt.
  • N-carbamoylglutamic acid is a structural analog of N-acetylglutamate (NAG), which is an activator of CPS-1 and intestinal dihydropyrrole-5-carboxylic acid synthase.
  • NCG can replace the NAG to activate CPS-1, increase the availability of carbamyl phosphate and ornithine in the intestine to promote the synthesis of citrulline and arginine; meanwhile, with NAG will be deacylated in cells
  • NCG is not a substrate for cell deacylation and amino acid metabolism enzymes, and its half-life is longer in vivo. Therefore, low dose of NCG can greatly increase the synthesis of arginine in the body and promote Protein synthesis promotes muscle growth.
  • NCG can easily enter cells and mitochondria, and it is non-toxic and non-auxiliary; it can also prevent complications of cirrhosis by hyperammonemia by strengthening the urea cycle in the liver.
  • NCG is not an antibiotic in terms of long-term tolerance, and has no inhibitory effect on intestinal microorganisms, and does not affect ammonia and other nitrogen supply precursors of these intestinal microorganisms. Effective utilization rate; unlike direct oral arginine, NCG does not affect the absorption of other amino acids in the diet such as tryptophan, histidine, lysine, etc., and maintains a balanced supply of arginine and other essential amino acids. .
  • the amino acid composition of the invention having liver protection and muscle growth promoting effect:
  • Vitamin B6 is a component of various coenzymes in the human body. It can participate in various metabolic reactions, improve the effects of fat exchange on atherosclerosis, prevent and treat acute and chronic liver diseases, and prevent and reduce the side effects of drugs. Glycine is mainly used as a blocker of endotoxin receptors in mononuclear macrophage membranes, thereby blocking intracellular signal transduction systems, making it difficult for endotoxin to exert biological effects, and significantly reducing plasma intestinal endotoxin levels. The damage was significantly alleviated and the liver function was significantly improved.
  • Zinc is a trace element in the presence of organisms. Many important enzymes such as insulin, adrenocorticotropic hormone, growth hormone, and gonadotropin are highly dependent on zinc. Zinc deficiency can weaken immunity and cause gastrointestinal diseases, liver diseases, kidney diseases, connective tissue diseases, blood diseases, etc. to occur easily.
  • Nicotinamide is a vitamin B3, which participates in the body's redox process, promotes blood circulation and lowers blood pressure. It also prevents heart block and improves sinus node function, and is used to prevent liver and heart diseases.
  • Taurine is a sulfur-containing conditionally essential amino acid. Taurine can inhibit platelet aggregation, reduce blood lipids, maintain normal blood pressure and prevent arteriosclerosis in the circulatory system; protect cardiomyocytes against arrhythmia; increase lipid and cholesterol solubility, reduce blood The medium cholesterol content has a special effect.
  • Succinic acid is a natural metabolic product of the human body. It is a metabolic tricarboxylic acid cycle with citric acid and oxaloacetate. With the exchange of weekly energy, the tricarboxylic acid cycle is the main way for the body to obtain energy. Succinic acid has the functions of anti-hypoxia, anti-oxidation and stimulating immunity. Under certain conditions, the following table has the effect of relieving alcoholism.
  • the present invention provides a health care product having liver protection and muscle growth promoting effects, comprising the above amino acid composition having liver protection and muscle growth promoting effect, and pharmacy.
  • the acceptable carrier is prepared according to conventional methods of pharmacy.
  • the dosage form of the health care product may be an oral preparation such as a tablet, a powder, a granule, a pill, a suspension, an emulsion, an infusion, a decoction, a capsule, a syrup or an elixir, or an injection, a drip, or an ointment.
  • oral preparation such as a tablet, a powder, a granule, a pill, a suspension, an emulsion, an infusion, a decoction, a capsule, a syrup or an elixir, or an injection, a drip, or an ointment.
  • Non-oral agents such as sitting agents.
  • Oral agents are preferred.
  • an additive such as an excipient, a binder, a breaker, a moisturizer, a dispersant, a suspending agent, an emulsifier, a diluent, a buffer, an antioxidant, a bacterial inhibitor or the like may be added.
  • a liquid preparation such as a syrup may be added, such as water, sugar such as sucrose, sorbitol or fructose, glycol such as polyethylene glycol or propylene glycol, oil such as sesame oil, olive oil or soybean oil, and antiseptic such as paraben.
  • a peroxybenzoic acid derivative such as methyl peroxybenzoate
  • a preservative such as benzoic acid
  • a flavor enhancer such as strawberry or mint.
  • Such as tableting agents, powders, granules, etc. can add sugars such as lactose, sugar, glucose, sucrose, mannitol, sorbitol, starch such as potato, wheat, corn, calcium carbonate, calcium sulfate, sodium bicarbonate, chlorination Inorganic substances such as sodium, plant powder excipients such as crystalline cellulose, licorice, gentian, starch, cold weather, gelatin powder, crystalline cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, calcium carbonate , sodium bicarbonate, sodium alginate and other breakers, magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol, silicone oil and other moisturizing agents, polyvinyl alcohol, hydroxypropyl cellulose, methyl cellulose, B A binder such as cellulose, carboxymethylcellulose, gelatin or starch paste, a surfactant such as a fatty acid ester, or a plasticizer such as glycerin.
  • oral preparations When making oral preparations, general food additives such as sweeteners, colorants, preservatives, viscosity stabilizers, antioxidants, color formers, bleaches, mildew inhibitors, gum bases, bittering agents, enzymes, etc., may also be added.
  • Oral preparations can also be used as powdered foods, flaky foods, bottled foods, canned foods, packaged foods, capsule foods, flakes, mobile foods, beverages, etc., as healthy foods, functional foods, and nutritional supplements for improving muscle labor. Use for food, etc.
  • the amino acid composition is composed by weight percentage:
  • Example 2 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • Example 2 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • Example 2 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • the amino acid composition is composed by weight percentage: N-carbamoyl glutamic acid 9.5%
  • Example 3 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • Example 3 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • the amino acid composition is composed by weight percentage:
  • Example 4 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • Example 4 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • Example 4 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • the amino acid composition is composed by weight percentage: 17.0%
  • Example 5 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • Example 5 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition.
  • the amino acid composition is composed by weight percentage:
  • 2-(dimethylamino)ethanol is an antioxidant and a precursor of the neurotransmitter acetylcholine (ACh). It plays a very important role in the initiation of sleep state.
  • 2-(Dimethylamino) ethanol supplementation is good for the human body.
  • 2-(dimethylamino)ethanol may be helpful in improving memory and learning ability.
  • 2- (dimethylamino) ethanol supplement can increase energy water Flat. It has a positive effect on sleep and stable mood.
  • the amino acid composition is composed by weight percentage:
  • the above-mentioned L-carnitine has many important functions: reducing fat, reducing body weight; helping the body burn fat during exercise, improving energy, endurance and exercise performance during exercise; removing excessive lactic acid, improving functional ability, promoting fatigue recovery Enhance the ability of cardiomyocytes to oxidize fat, reduce the burden on the heart during high-intensity exercise; slow down the aging process of humans and so on.
  • Test example
  • mice Four experimental groups of 1, 2, 3, and 4 were set, plus normal control group and liver injury model group.
  • the normal control group and the liver injury model group were subjected to distilled water, the first, second, and third experimental groups were respectively given the amino acid compositions prepared in Examples 1, 2, and 3, and the experimental group was given N-carbamoyl glutamic acid.
  • the daily dose is 5 mg/kg, 50 mg/kg, 100 mg/kg, respectively, based on N-carbamoylglutamic acid. And 150mg/kg for 28 consecutive days.
  • 1, 2, 3, 4 experimental group and liver injury model group were exposed to CC1 4 at a dose of 25 mg/kg, intraperitoneal injection.
  • mice Male SD rats 200-250g
  • Experimental method Rat models of renovascular hypertension were replicated by two kidneys and one clip method. Thirty rats with successful modeling were randomly divided into 1, 2, 3, and 4 rats.
  • 6 rats in each group and 6 rats in the sham operation group 1, 3, 3 rats of the three experimental groups were given the amino acid compositions prepared in Examples 1, 2, and 3, respectively, and 4 experimental groups were given N-carbamoyl glutamic acid, and the daily dose was N-ammonia.
  • Formyl glutamic acid was 5 mg/kg, 50 mg/kg, 100 mg/kg, and 150 mg/kg, respectively.
  • Model control and sham operation group Distilled water was given for 4 weeks, and blood pressure was measured every week. The experimental results are as follows. Blood pressure after administration
  • High-fat and high-nutrition feed Cg cholesterol lg, bile salt 0.5g, lard 10g, egg yolk powder 10g per 100g of basic feed.
  • mice 30 rats were taken. After 5 days of feeding with normal diet, tail blood was taken and the basic values of serum triglyceride, cholesterol and high density lipoprotein were measured. Then, the rats were randomly divided into four groups of 1, 2, 3, and 4 and a high-fat model control group according to the basal blood lipid level, and 6 rats in each group. 1, 2, 3 three experimental groups were given the amino acid composition prepared in Examples 1, 2, and 3, respectively, 4 experimental group was given N-carbamoyl glutamic acid, and the daily dose was N-carbamoylglutamic acid. The samples were 5mg/kg, 50mg/kg, 100mg/kg, 150mg/kg, respectively .
  • the high-fat model group was given distilled water, and each group was fed with high-fat and high-nutrition feed. After 28 days of continuous feeding, the blood samples of the rats were taken for blood lipid levels.
  • the experimental results are as follows: Effects on animal cholesterol: Cholesterol (mmol/L) group of animals
  • Model control group 6 1.75 ⁇ 0.15 3.54 ⁇ 0.41
  • Model control group 6 1.08 ⁇ 0.07 3.63 ⁇ 0.54
  • Model control group 6 0.81 ⁇ 0.09 0.73 ⁇ 0.08
  • mice SD rats 80-100g
  • Experimental methods 30 rats were randomly divided into 1, 2, 3, 4 experimental group and normal control group, 6 rats in each group. 1, 2, 3 experimental groups were given respectively in Examples 1, 2, 3
  • the amino acid composition, 4 experimental group gave N-carbamoylglutamic acid, and the daily dose was 5 mg/kg, 50 mg/kg, 100 mg/kg and 150 mg/kg, respectively, based on N-carbamoylglutamic acid. Feeded on normal feed for 4 weeks. The changes in body weight of the rats were observed, and the muscle tissue components of the rats were analyzed.

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Abstract

Use of N-carbamyl glutamic acid, salts or esters thereof in the manufacture of health care products for protecting liver or promoting muscle growth is provided in the present invention. N-carbamoyl glutamic acid can prevent and treat hyperazotemia, a liver cirrhosis complication, through increasing urea cycle in liver, and increase synthesis of arginine in the body, promote synthesis of proteins and muscle growth in low dose. Amino acids compositions and health care products for protecting liver or promoting muscle growth, consisting of N-carbamoyl glutamic acid, salts or esters thereof, arginine, salts or esters thereof, pyridoxine hydrochloride, glycine, compounds containing zinc, micotinamide, taurine, and succinic acid are also provided in the present invention.

Description

N-氨甲酰谷氨酸、 其盐或其酯在制备护肝、 促肌肉生长保健品中的应用 技术领域  Application of N-carbamoylglutamic acid, its salt or ester thereof in preparing liver protection and muscle growth promoting health care products
本发明属于保健品技术领域， 具体涉及 N-氨甲酰谷氨酸、其盐或其酯在 制备护肝、 促肌肉生长保健品中的应用。 背景技术  The invention belongs to the technical field of health care products, and particularly relates to the application of N-carbamoylglutamic acid, a salt thereof or an ester thereof for preparing a liver-protecting and muscle-promoting health care product. Background technique
精氨酸在哺乳动物体内具有重要的营养作用， 精氨酸缺乏已被认为是生 长的限制因素， 氨甲酰磷酸合成酶 -l(CPS-l)是精氨酸内源合成的限速酶， 在 鸟氨酸和瓜氨酸转化为精氨酸的过程中起到很大作用。 已知 N-乙酰谷氨酸 (NAG)是 CPS- 1的激活剂， 可激活 CPS-1 , 进而增加精氨酸的内源合成。 体 内 NAG含量的高低主要取决于两方面因素： 首先， 体内 NAG的合成需要 NAG合成酶， 该酶的缺乏会使体内没有足够的 NAG供应； 另外， 哺乳动物 的细胞溶质中含有高活性的脱酰酶， 它会分解 NAG, 由此降低体内 NAG的 含量， 进而影响精氨酸的内源合成。  Arginine has an important nutritional role in mammals. Arginine deficiency has been considered as a limiting factor for growth. Carbamoyl phosphate synthase-1 (CPS-1) is the rate-limiting enzyme for endogenous synthesis of arginine. , plays a big role in the conversion of ornithine and citrulline to arginine. N-acetylglutamate (NAG) is known to act as an activator of CPS-1, which activates CPS-1, thereby increasing the endogenous synthesis of arginine. The level of NAG in the body depends mainly on two factors: First, the synthesis of NAG in vivo requires NAG synthase, which lacks sufficient NAG supply in the body; in addition, mammalian cytosol contains highly active deacyl Enzyme, which decomposes NAG, thereby reducing the amount of NAG in the body, which in turn affects the endogenous synthesis of arginine.
N-氨甲酰谷氨酸（NCG)是 NAG的结构类似物， 公开号为 CN101481336 的中国专利申请提供了由谷氨酸与尿素反应制备 N-氨甲酰谷氨酸的方法。  N-carbamoylglutamic acid (NCG) is a structural analog of NAG, and Chinese Patent Application Publication No. CN101481336 provides a method for preparing N-carbamoylglutamic acid by reacting glutamic acid with urea.
发明内容 Summary of the invention
本发明的目的在于提供 N-氨甲酰谷氨酸、其盐或其酯在制备护肝、促肌 肉生长保健品中的应用。  SUMMARY OF THE INVENTION An object of the present invention is to provide an application of N-carbamoylglutamic acid, a salt thereof or an ester thereof for the preparation of a liver-protecting and muscle-promoting growth health product.
本发明的另一个目的在于提供一种包含 N-氨甲酰谷氨酸、 其盐或其酯 的， 具有护肝、 促肌肉生长作用的氨基酸组合物。 本发明的还一个目的在于提供一种具有护肝、促肌肉生长作用的保健品。 根据本发明的一个目的， 本发明提供了 N-氨甲酰谷氨酸、其盐或其酯在 制备护肝、 促肌肉生长保健品中的应用。 Another object of the present invention is to provide an amino acid composition comprising N-carbamoylglutamic acid, a salt thereof or an ester thereof, which has a liver-protecting effect and a muscle-promoting action. Still another object of the present invention is to provide a health care product having liver protection and muscle growth promoting effects. According to one object of the present invention, the present invention provides the use of N-carbamoylglutamic acid, a salt thereof or an ester thereof for the preparation of a liver-protecting, muscle-promoting health-care product.
其中， 所述 N-氨甲酰谷氨酸为 L-型； 所述 N-氨甲酰谷氨酸的盐是无机 酸盐、 有机酸盐、 金属盐、 铵盐、 有机铵盐或氨基酸盐； N-氨甲酰谷氨酸的 的酯是低级醇酯， 优选甲酯或乙酯。 根据本发明的另一个目的， 本发明提供的具有护肝、 促肌肉生长作用的 氨基酸组合物， 按重量百分含量计， 由以下组分组成：  Wherein the N-carbamoylglutamic acid is L-form; the salt of the N-carbamoylglutamic acid is a mineral acid salt, an organic acid salt, a metal salt, an ammonium salt, an organic ammonium salt or an amino acid salt The ester of N-carbamoylglutamic acid is a lower alcohol ester, preferably a methyl or ethyl ester. According to another object of the present invention, the amino acid composition having liver protection and muscle growth promoting effect provided by the present invention comprises, by weight percent, the following components:
N-氨甲酰谷氨酸、 其盐或其酯 0.92-18.00%； 精氨酸、 其盐或其酯 0.80-17.00%； 盐酸吡哆辛 （维生素 B6) 0.10-1.70%； 甘氨酸 4.50-32.00%； 含锌化合物 1.35-2.70%； 烟酰胺 .50-7.50%； 牛磺酸 N-carbamoylglutamic acid, its salt or its ester 0.92-18.00%; arginine, its salt or its ester 0.80-17.00%; pyridoxine hydrochloride (vitamin B6) 0.10-1.70%; glycine 4.50-32.00 %; zinc-containing compound 1.35-2.70%; nicotinamide. 50-7.50%; taurine
琥珀酸
Figure imgf000003_0001
Succinic acid
Figure imgf000003_0001
其中， 所述含锌化合物为二水合醋酸锌或柠檬酸锌;  Wherein the zinc-containing compound is zinc acetate dihydrate or zinc citrate;
所述 N-氨甲酰谷氨酸的盐、精氨酸的盐是无机酸盐、有机酸盐、金属盐、 铵盐、 有机铵盐或氨基酸盐； 所述 N-氨甲酰谷氨酸的酯、 精氨酸的酯是低级 醇酯， 优选甲酯或乙酯。  The salt of N-carbamoylglutamic acid or the salt of arginine is a mineral acid salt, an organic acid salt, a metal salt, an ammonium salt, an organic ammonium salt or an amino acid salt; the N-carbamoyl glutamic acid The ester, ester of arginine is a lower alcohol ester, preferably a methyl or ethyl ester.
上述无机酸盐可以是盐酸盐、 硫酸盐、 硝酸盐、 磷酸盐等。  The above inorganic acid salt may be a hydrochloride, a sulfate, a nitrate, a phosphate or the like.
有机酸盐可以是醋酸盐、 马来酸盐、 富马酸盐、 柠檬酸盐、 苹果酸盐- 乳酸盐、 α-酮基戊二酸盐、 葡糖酸、 辛酸盐等。 金属盐可以是钠盐、钾盐等碱金属盐， 镁盐、钙盐等碱土金属盐， 铝盐、 锌盐等。 The organic acid salt may be acetate, maleate, fumarate, citrate, malate-lactate, alpha-ketoglutarate, gluconic acid, octanoate or the like. The metal salt may be an alkali metal salt such as a sodium salt or a potassium salt, an alkaline earth metal salt such as a magnesium salt or a calcium salt, an aluminum salt or a zinc salt.
有机铵盐可以是吗啉盐或哌啶盐等。  The organic ammonium salt may be a morpholine salt or a piperidine salt or the like.
氨基酸盐可以是甘氨酸盐、 苯丙氨酸盐、 赖氨酸盐或天冬氨酸盐。 本发明中， N-氨甲酰谷氨酸 （NCG) 作为 N-乙酰谷氨酸 （NAG) 的结 构类似物， 为 CPS-1和肠内二氢吡咯 -5-羧酸合成酶的激活剂， 可替代 NAG 发挥激活 CPS-1的作用， 增加肠道内氨甲酰磷酸和鸟氨酸的有效性而促进瓜 氨酸和精氨酸的合成； 同时， 与 NAG会被细胞中的脱酰酶分解的特性不同， NCG不是细胞脱酰酶和氨基酸代谢酶的作用底物， 它在体内的半衰期较长， 因此低剂量的 NCG就能对增加体内精氨酸的合成产生很大的效果， 促进蛋 白质的合成， 促进肌肉生长。  The amino acid salt can be a glycinate, a phenylalanine salt, a lysine salt or an aspartate salt. In the present invention, N-carbamoylglutamic acid (NCG) is a structural analog of N-acetylglutamate (NAG), which is an activator of CPS-1 and intestinal dihydropyrrole-5-carboxylic acid synthase. , can replace the NAG to activate CPS-1, increase the availability of carbamyl phosphate and ornithine in the intestine to promote the synthesis of citrulline and arginine; meanwhile, with NAG will be deacylated in cells Different from the characteristics of decomposition, NCG is not a substrate for cell deacylation and amino acid metabolism enzymes, and its half-life is longer in vivo. Therefore, low dose of NCG can greatly increase the synthesis of arginine in the body and promote Protein synthesis promotes muscle growth.
此外， NCG能轻易进入细胞和线粒体中发挥作用， 而且它是无毒无副作 用的； 还可通过加强肝脏中的尿素循环来防治肝硬化的并发症高氨血症。  In addition, NCG can easily enter cells and mitochondria, and it is non-toxic and non-auxiliary; it can also prevent complications of cirrhosis by hyperammonemia by strengthening the urea cycle in the liver.
同时， 作为用于制备保健品的组合物， 在长期服用的耐受性方面， NCG 不是抗生素， 对肠内的微生物没有抑制作用， 而且不会影响这些肠内微生物 的氨及其他氮供应前体的有效利用率； 与直接口服精氨酸不同， NCG也不会 影响膳食中其它氨基酸如色氨酸、 组氨酸、 赖氨酸等的吸收， 能保持精氨酸 与其它必需氨基酸的平衡供应。 本发明的具有护肝、 促肌肉生长作用的氨基酸组合物中：  At the same time, as a composition for the preparation of health care products, NCG is not an antibiotic in terms of long-term tolerance, and has no inhibitory effect on intestinal microorganisms, and does not affect ammonia and other nitrogen supply precursors of these intestinal microorganisms. Effective utilization rate; unlike direct oral arginine, NCG does not affect the absorption of other amino acids in the diet such as tryptophan, histidine, lysine, etc., and maintains a balanced supply of arginine and other essential amino acids. . The amino acid composition of the invention having liver protection and muscle growth promoting effect:
维生素 B6为人体内多种辅酶的组成成分， 参与多种代谢反应， 能改善 脂肪交换影响动脉粥样硬化、 用于防治急慢性肝病， 并可预防和减轻药物的 毒副作用。 甘氨酸主要作用是单核巨噬细胞膜内毒素受体的阻滞剂， 从而阻断细胞 内信号转导系统， 使内毒素难以发挥生物学效应， 具有明显降低血浆肠源性 内毒素水平， 使肝损伤明显减轻， 肝功能得到明显改善。 Vitamin B6 is a component of various coenzymes in the human body. It can participate in various metabolic reactions, improve the effects of fat exchange on atherosclerosis, prevent and treat acute and chronic liver diseases, and prevent and reduce the side effects of drugs. Glycine is mainly used as a blocker of endotoxin receptors in mononuclear macrophage membranes, thereby blocking intracellular signal transduction systems, making it difficult for endotoxin to exert biological effects, and significantly reducing plasma intestinal endotoxin levels. The damage was significantly alleviated and the liver function was significantly improved.
锌是有机体存在的微量元素， 许多重要的酶如胰岛素、 促肾上腺皮质激 素、生长激素、促性腺激素等对锌都有很大的依赖性。缺锌会减弱免疫能力， 会使胃肠道疾病、 肝脏疾病、 肾脏疾病、 结缔组织系统疾病、 血液疾病等等 容易发生。  Zinc is a trace element in the presence of organisms. Many important enzymes such as insulin, adrenocorticotropic hormone, growth hormone, and gonadotropin are highly dependent on zinc. Zinc deficiency can weaken immunity and cause gastrointestinal diseases, liver diseases, kidney diseases, connective tissue diseases, blood diseases, etc. to occur easily.
烟酰胺别名维生素 B3， 它参与机体的氧化还原过程， 促进血液循环， 使 血压下降； 还有防治心脏传导阻滞和提高窦房结功能的作用， 用于防治肝脏 和心脏的疾病。  Nicotinamide is a vitamin B3, which participates in the body's redox process, promotes blood circulation and lowers blood pressure. It also prevents heart block and improves sinus node function, and is used to prevent liver and heart diseases.
牛磺酸 (taurine)是一种含硫条件性必需氨基酸。牛磺酸在循环系统中可抑 制血小板凝集， 降低血脂， 保持人体正常血压和防止动脉硬化； 对心肌细胞 有保护作用， 可抗心律失常； 还能增加脂质和胆固醇的溶解性， 对降低血液 中胆固醇含量有特殊疗效。  Taurine is a sulfur-containing conditionally essential amino acid. Taurine can inhibit platelet aggregation, reduce blood lipids, maintain normal blood pressure and prevent arteriosclerosis in the circulatory system; protect cardiomyocytes against arrhythmia; increase lipid and cholesterol solubility, reduce blood The medium cholesterol content has a special effect.
琥珀酸是人体自然代谢的产物， 它与柠檬酸和草酰乙酸构成代谢的三羧 酸循环， 伴随周能量交换， 三羧酸循环是机体获取能量的主要方式。 琥珀酸 具有反缺氧、 抗氧化和刺激免疫等功能， 在一定条件下表现有解除酒精中毒 的的功效。  Succinic acid is a natural metabolic product of the human body. It is a metabolic tricarboxylic acid cycle with citric acid and oxaloacetate. With the exchange of weekly energy, the tricarboxylic acid cycle is the main way for the body to obtain energy. Succinic acid has the functions of anti-hypoxia, anti-oxidation and stimulating immunity. Under certain conditions, the following table has the effect of relieving alcoholism.
这些成分合在一起使用， 由于协同作用， 会比单个使用发挥出更大的效 果。 因而配方中的使用量比单独使用单一个成分更少。 根据本发明的另一个目的， 本发明提供了一种具有护肝、 促肌肉生长作 用的保健品， 其包含上述具有护肝、 促肌肉生长作用的氨基酸组合物和药学 上可接受的载体， 按照药剂学常规方法制成。 These ingredients are used together and, due to synergy, will perform more than a single use. Thus the amount used in the formulation is less than the single component used alone. According to another object of the present invention, the present invention provides a health care product having liver protection and muscle growth promoting effects, comprising the above amino acid composition having liver protection and muscle growth promoting effect, and pharmacy. The acceptable carrier is prepared according to conventional methods of pharmacy.
所述保健品的剂型可以是锭剂、 散剂、 颗粒剂、 丸剂、 悬浊剂、 乳剂、 浸剂、 煎剂、 胶囊剂、 糖浆、 酊剂等口服剂， 也可以是注射剂、 点滴剂、 膏 剂、 坐剂等非口服剂。 以口服剂较好。  The dosage form of the health care product may be an oral preparation such as a tablet, a powder, a granule, a pill, a suspension, an emulsion, an infusion, a decoction, a capsule, a syrup or an elixir, or an injection, a drip, or an ointment. Non-oral agents such as sitting agents. Oral agents are preferred.
口服剂制剂时， 可以添加赋形剂、 结合剂、 崩坏剂、 润泽剂、 分散剂、 悬浊剂、 乳化剂、 稀释剂、 缓冲剂、 抗氧化剂、 细菌抑制剂等添加剂。  In the case of an oral preparation, an additive such as an excipient, a binder, a breaker, a moisturizer, a dispersant, a suspending agent, an emulsifier, a diluent, a buffer, an antioxidant, a bacterial inhibitor or the like may be added.
例如配制糖浆剂这样的液体制剂， 可以添加水、 蔗糖、 山梨醇、 果糖等 糖类， 聚乙二醇、 丙二醇等二元醇， 芝麻油、 橄榄油、 大豆油等油类， 尼泊 金等防腐剂， 过氧苯甲酸甲酯等过氧苯甲酸衍生物， 苯甲酸等保存剂， 草莓 味、 薄荷味等增味剂。  For example, a liquid preparation such as a syrup may be added, such as water, sugar such as sucrose, sorbitol or fructose, glycol such as polyethylene glycol or propylene glycol, oil such as sesame oil, olive oil or soybean oil, and antiseptic such as paraben. a peroxybenzoic acid derivative such as methyl peroxybenzoate, a preservative such as benzoic acid, or a flavor enhancer such as strawberry or mint.
如制锭剂、 散剂、 颗粒剂等， 可以添加乳糖、 白糖、 葡萄糖、 蔗糖、 甘 露醇、 山梨醇等糖类， 马铃薯、 小麦、 玉米等淀粉， 碳酸钙、 硫酸钙、 碳酸 氢钠、 氯化钠等无机物， 结晶纤维素、 甘草末、 龙胆末等植物粉末赋形剂， 淀粉、 寒天、 明胶粉、 结晶纤维素、 羧甲基纤维素钠、 羧甲基纤维素钙、 碳 酸钙、 碳酸氢钠、 藻酸钠等崩坏剂， 硬脂酸镁、 滑石粉、 氢化植物油、 聚乙 二醇、 硅油等润泽剂， 聚乙烯醇、 羟丙基纤维素、 甲基纤维素、 乙基纤维素、 羧甲基纤维素、 明胶、 淀粉糊等结合剂， 脂肪酸酯等表面活性剂， 甘油等可 塑剂。  Such as tableting agents, powders, granules, etc., can add sugars such as lactose, sugar, glucose, sucrose, mannitol, sorbitol, starch such as potato, wheat, corn, calcium carbonate, calcium sulfate, sodium bicarbonate, chlorination Inorganic substances such as sodium, plant powder excipients such as crystalline cellulose, licorice, gentian, starch, cold weather, gelatin powder, crystalline cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, calcium carbonate , sodium bicarbonate, sodium alginate and other breakers, magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol, silicone oil and other moisturizing agents, polyvinyl alcohol, hydroxypropyl cellulose, methyl cellulose, B A binder such as cellulose, carboxymethylcellulose, gelatin or starch paste, a surfactant such as a fatty acid ester, or a plasticizer such as glycerin.
制造口服制剂时， 还可加入一般食品添加剂， 如甜味剂， 着色剂， 保存 剂， 增粘稳定剂， 防氧化剂， 发色剂， 漂白剂， 防霉剂， 胶基， 苦味剂， 酶， 光泽剂， 酸味剂， 调味料， 乳化剂， 强化剂， 制造用剂， 香料， 香辛料抽提 物等。 口服制剂还可以做成粉末食品、 薄片状食品、 瓶装食品、 罐头食品、 包装食品、 胶囊食品、 片状食品、 流动食品、 饮料等形态， 作为改善肌肉 劳用的健康食品、 功能食品、 营养补助食品等使用。 When making oral preparations, general food additives such as sweeteners, colorants, preservatives, viscosity stabilizers, antioxidants, color formers, bleaches, mildew inhibitors, gum bases, bittering agents, enzymes, etc., may also be added. A glossing agent, a sour agent, a seasoning, an emulsifier, a strengthening agent, a manufacturing agent, a fragrance, a spice extract, and the like. Oral preparations can also be used as powdered foods, flaky foods, bottled foods, canned foods, packaged foods, capsule foods, flakes, mobile foods, beverages, etc., as healthy foods, functional foods, and nutritional supplements for improving muscle labor. Use for food, etc.
具体实施方式 detailed description
下面结合具体实施实例对本发明作进一歩阐述， 但不限制本发明。 通过下面给出的本发明的具体实施例可以进一歩清楚地了解本发明。但 它们不是对本发明的限定。  The present invention will be further described below in conjunction with specific embodiments, without limiting the invention. The invention will be apparent from the following detailed description of the embodiments of the invention. However, they are not intended to limit the invention.
制备实施例  Preparation example
实施例 1  Example 1
氨基酸组合物， 按重量百分比组成为：  The amino acid composition is composed by weight percentage:
0.92%  0.92%
0.80%  0.80%
0.10%  0.10%
18.50%  18.50%
1.35%  1.35%
3.50%  3.50%
1.20%  1.20%
按照上述含量配比称取各组分， 混合后研磨均匀， 制成氨基酸组合物。 实施例 2 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition. Example 2
氨基酸组合物， 按重量百分比组成为： N-氨甲酰谷氨酸 9.5% The amino acid composition is composed by weight percentage: N-carbamoyl glutamic acid 9.5%
精氨酸 9.0%  Arginine 9.0%
盐酸吡哆辛 0.85%  Pyridoxine hydrochloride 0.85%
甘氨酸 4.50%  Glycine 4.50%
二水合醋酸锌 2.025%  Zinc acetate dihydrate 2.025%
烟酰胺 6.20%  Nicotinamide 6.20%
牛磺酸 37.0%  Taurine 37.0%
琥珀酸 全骨里  Succinic acid
按照上述含量配比称取各组分， 混合后研磨均匀， 制成氨基酸组合物。 实施例 3 The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition. Example 3
氨基酸组合物， 按重量百分比组成为： The amino acid composition is composed by weight percentage:
Ν-氨甲酰谷氨酸 18.0%  Ν-carbamoyl glutamic acid 18.0%
精氨酸 17.0%  Arginine 17.0%
盐酸吡哆辛 1.70%  Pyridoxine hydrochloride 1.70%
甘氨酸 32.0%  Glycine 32.0%
二水合醋酸锌 2.70%  Zinc acetate dihydrate 2.70%
烟酰胺 7.50%  Nicotinamide 7.50%
牛磺酸 19.35%  Taurine 19.35%
琥珀酸 全骨里  Succinic acid
按照上述含量配比称取各组分， 混合后研磨均匀， 制成氨基酸组合物。 实施例 4  The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition. Example 4
氨基酸组合物， 按重量百分比组成为： 17.0% The amino acid composition is composed by weight percentage: 17.0%
盐酸吡哆辛 1.70%  Pyridoxine hydrochloride 1.70%
甘氨酸 32.0%  Glycine 32.0%
二水合醋酸锌 2.70%  Zinc acetate dihydrate 2.70%
烟酰胺 7.50%  Nicotinamide 7.50%
牛磺酸 19.35%  Taurine 19.35%
琥珀酸  Succinic acid
按照上述含量配比称取各组分， 混合后研磨均匀， 制成氨基酸组合物, 实施例 5  The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition. Example 5
氨基酸组合物， 按重量百分比组成为:  The amino acid composition is composed by weight percentage:
N-氨甲酰谷氨酸 12.0%  N-carbamoyl glutamic acid 12.0%
精氨酸 11.0%  Arginine 11.0%
2- (二甲氨基） 乙醇 10.70%  2-(dimethylamino)ethanol 10.70%
碳酸钙 11.2%  Calcium carbonate 11.2%
淀粉 5.25%  Starch 5.25%
微晶纤维素 余量  Microcrystalline cellulose
按照上述含量配比称取各组分， 混合后研磨均匀， 制成氨基酸组合物。 其中， 上述的 2- (二甲氨基） 乙醇， 简称 DMAE, 是一种抗氧化剂和 神经递质乙酰胆碱 (ACh)的前体。 对睡眠状态的启动起着非常重要的作用。 2- (二甲氨基） 乙醇补充对人体是有好处的。 例如， 2- (二甲氨基） 乙醇可 能对改善记忆和学习能力有帮助。 2- (二甲氨基） 乙醇补充能够增加能量水 平。 它可对睡眠和稳定情绪有正性效应。 实施例 ό The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition. Among them, the above 2-(dimethylamino)ethanol, abbreviated as DMAE, is an antioxidant and a precursor of the neurotransmitter acetylcholine (ACh). It plays a very important role in the initiation of sleep state. 2-(Dimethylamino) ethanol supplementation is good for the human body. For example, 2-(dimethylamino)ethanol may be helpful in improving memory and learning ability. 2- (dimethylamino) ethanol supplement can increase energy water Flat. It has a positive effect on sleep and stable mood. Example
氨基酸组合物， 按重量百分比组成为:  The amino acid composition is composed by weight percentage:
左旋肉碱 L-carnitine
苯甲酸钠  sodium benzoate
葡萄糖  Glucose
按照上述含量配比称取各组分， 混合后研磨均匀， 制成氨基酸组合物。 其中， 上述的左旋肉碱具有许多重要作用： 减少脂肪， 降低体重； 在运 动时帮助身体燃烧脂肪， 提高运动时的能量、 耐力和运动成绩； 清除过多乳 酸， 提高做功能力， 促进疲劳恢复； 增强心肌细胞氧化脂肪的能力， 降低高 强度运动时心脏的负担； 减慢人的衰老过程等等。 测试实施例  The components were weighed according to the above content ratio, mixed and ground uniformly to prepare an amino acid composition. Among them, the above-mentioned L-carnitine has many important functions: reducing fat, reducing body weight; helping the body burn fat during exercise, improving energy, endurance and exercise performance during exercise; removing excessive lactic acid, improving functional ability, promoting fatigue recovery Enhance the ability of cardiomyocytes to oxidize fat, reduce the burden on the heart during high-intensity exercise; slow down the aging process of humans and so on. Test example
实施例 7  Example 7
对化学性肝损伤的辅助保护作用  Auxiliary protection against chemical liver injury
实验动物： 雄性 SD大鼠 200-250g  Experimental animals: Male SD rats 200-250g
实验方法及结果： 设置 1、 2、 3、 4四个实验组， 另加正常对照组和肝损 伤模型组。 正常对照组和肝损伤模型组饮用蒸馏水， 1、 2、 3 三个实验组分 别给予由实施例 1， 2， 3制得的氨基酸组合物， 4实验组给予 N-氨甲酰谷氨 酸， 每天的剂量以 N-氨甲酰谷氨酸计分别为 5mg/kg， 50mg/kg、 100mg/kg 和 150mg/kg， 连续 28天。第 28天 1、 2、 3、 4实验组和肝损伤模型组用 CC14 染毒， 剂量为 25mg/kg， 腹腔注射。 第 29天， 5组动物摘眼球取血， 离心， 取血清。 测定下述生化指标： 血清谷丙转氨酶 (GPT)、 谷草转氨酶 （GOT)。 实验结果用 STATA软件进行统计。 Experimental methods and results: Four experimental groups of 1, 2, 3, and 4 were set, plus normal control group and liver injury model group. The normal control group and the liver injury model group were subjected to distilled water, the first, second, and third experimental groups were respectively given the amino acid compositions prepared in Examples 1, 2, and 3, and the experimental group was given N-carbamoyl glutamic acid. The daily dose is 5 mg/kg, 50 mg/kg, 100 mg/kg, respectively, based on N-carbamoylglutamic acid. And 150mg/kg for 28 consecutive days. On day 28, 1, 2, 3, 4 experimental group and liver injury model group were exposed to CC1 4 at a dose of 25 mg/kg, intraperitoneal injection. On the 29th day, 5 groups of animals were taken from the eyeballs for blood collection, centrifuged, and serum was taken. The following biochemical indicators were determined: serum alanine aminotransferase (GPT) and aspartate aminotransferase (GOT). The experimental results were statistically analyzed using STATA software.
~~动物组别 动物数 谷丙转氨酶 谷草转氨酶 ~ ~~Animal group Animal number Alanine aminotransferase Aspartate aminotransferase ~
( ) (IU/L) (IU/L)  ( ) (IU/L) (IU/L)
正常对照 6 47 ± 13 90 ± 17  Normal control 6 47 ± 13 90 ± 17
CC14模型 6 1021 ±247 983 ±429 CC1 4 model 6 1021 ± 247 983 ± 429
1实验组 6 295 ±25 305 ±44  1 experimental group 6 295 ± 25 305 ± 44
2实验组 6 762 ± 189 638 ± 179  2 experimental group 6 762 ± 189 638 ± 179
3实验组 6 732 ±201 603 ± 156  3 experimental group 6 732 ± 201 603 ± 156
4实验组 6 741 ± 187 612 ± 163 对实验数据的统计分析表明， 与 CC 肝损伤模型组相比较， N-氨甲酰谷 氨酸以及实施例 1， 2， 3所制得的氨基酸组合物都能够明显减轻肝损伤的程 度（P值均小于 0.05)， 其中以实施例 1所制得的氨基酸组合物的作用最为明 显。 实施例 8 对心血管系统的保护作用 1. 降血压作用  4 Experimental group 6 741 ± 187 612 ± 163 Statistical analysis of the experimental data showed that N-carbamoylglutamic acid and the amino acid compositions prepared in Examples 1, 2, 3 were compared with the CC liver injury model group. Both can significantly reduce the degree of liver damage (P value is less than 0.05), wherein the amino acid composition prepared in Example 1 has the most obvious effect. Example 8 Protection of the cardiovascular system 1. Blood pressure lowering effect
实验动物： 雄性 SD大鼠 200-250g 实验方法： 采用两肾一夹法复制肾血管性高血压大鼠模型， 取 30只造模成功 的大鼠随机分为 1、 2、 3、 4四个实验组及模型对照组， 每组 6只， 另取 6只作 为假手术组。 1、 2、 3三个实验组的大鼠分别每日给予实施例 1、 2、 3制得的 氨基酸组合物， 4实验组给 N-氨甲酰谷氨酸， 每天的剂量以 N-氨甲酰谷氨酸 计分别为 5mg/kg， 50mg/kg、 100mg/kg, 150mg/kg。 模型对照及假手术组给 予蒸馏水， 连续 4周， 每周测量血压， 实验结果如下。 给药后血压 Experimental animals: Male SD rats 200-250g Experimental method: Rat models of renovascular hypertension were replicated by two kidneys and one clip method. Thirty rats with successful modeling were randomly divided into 1, 2, 3, and 4 rats. In the experimental group and the model control group, 6 rats in each group and 6 rats in the sham operation group. 1, 3, 3 rats of the three experimental groups were given the amino acid compositions prepared in Examples 1, 2, and 3, respectively, and 4 experimental groups were given N-carbamoyl glutamic acid, and the daily dose was N-ammonia. Formyl glutamic acid was 5 mg/kg, 50 mg/kg, 100 mg/kg, and 150 mg/kg, respectively. Model control and sham operation group Distilled water was given for 4 weeks, and blood pressure was measured every week. The experimental results are as follows. Blood pressure after administration
组别 给药前血压 1周 2周 3周 4周  Group Pre-dose blood pressure 1 week 2 weeks 3 weeks 4 weeks
假手术组 125.6±6.38 125.7±6.04 128.9±8.32 127.0±6.74 126.4±4.32 模型组 181.6±16.7 182.2±11.28 183.9± 13.28 179.4±10.7 176.8±8.75  Sham operation group 125.6±6.38 125.7±6.04 128.9±8.32 127.0±6.74 126.4±4.32 Model group 181.6±16.7 182.2±11.28 183.9± 13.28 179.4±10.7 176.8±8.75
1实验组 189.5 ±20.82 178.8±24.1 170.6±16.4 165.8±10.2 158.7±7.58  1 experimental group 189.5 ± 20.82 178.8 ± 24.1 170.6 ± 16.4 165.8 ± 10.2 158.7 ± 7.58
2实验组 185.9± 14.52 175.8±24.1 165.1 ±18.6 156.4±10.7 144.4±8.13  2 experimental group 185.9 ± 14.52 175.8 ± 24.1 165.1 ± 18.6 156.4 ± 10.7 144.4 ± 8.13
3实验组 190.3 ±16.55 181.4±9.37 172.9±9.65 163.3±5.56 154.9±3.39  3 experimental group 190.3 ± 16.55 181.4 ± 9.37 172.9 ± 9.65 163.3 ± 5.56 154.9 ± 3.39
4实验组 189.2+15.28 180.57±8.74 178.8±9.21 177.8±6.23 176.7±4.33 对实验数据的统计分析表明， 单独的 N-氨甲酰谷氨酸没有明显的降血压 作用， 而实施例 1、 2、 3 所制得的氨基酸组合物都有明显的降血压作用 （P 值均小于 0.05)，其中以实施例 2所制得的氨基酸组合物的降血压效果最为明 显。  4 Experimental group 189.2+15.28 180.57±8.74 178.8±9.21 177.8±6.23 176.7±4.33 Statistical analysis of the experimental data showed that N-carbamylglutamic acid alone had no significant blood pressure lowering effect, but Examples 1, 2, 3 The amino acid compositions prepared have obvious blood pressure lowering effects (P values are less than 0.05), and the amino acid composition prepared in Example 2 has the most obvious blood pressure lowering effect.
2. 降血脂作用 2. Lowering blood fat
实验动物： 雄性 SD大鼠 150-200g Experimental animals: Male SD rats 150-200g
高脂高营养饲料： 每 100克基础饲料中加胆固醇 lg， 胆盐 0.5g， 猪油 10g， 蛋黄粉 10g。 High-fat and high-nutrition feed: Cg cholesterol lg, bile salt 0.5g, lard 10g, egg yolk powder 10g per 100g of basic feed.
实验方法：取大鼠 30只， 以普通饲料喂养 5天后，取尾血，测血清甘油三酯、 胆固醇、 高密度脂蛋白的基础值。 然后根据基础血脂水平将大鼠随机分为 1、 2、 3、 4四个实验组及高脂模型对照组， 每组 6只大鼠。 1、 2、 3三个实验组 分别给予实施例 1， 2， 3制得的氨基酸组合物， 4实验组给 N-氨甲酰谷氨酸， 每天的剂量以 N-氨甲酰谷氨酸计分别为 5mg/kg， 50mg/kg、 100mg/kg, 150mg/kg; 高脂模型组则给予蒸馏水， 每组均饲以高脂高营养饲料。 连续喂 养 28天后， 取大鼠眼血测各项血脂指标。 实验结果如下： 对动物胆固醇的影响： 胆固醇 （mmol/L) 组别 动物数 实验前 实验末 Experimental method: 30 rats were taken. After 5 days of feeding with normal diet, tail blood was taken and the basic values of serum triglyceride, cholesterol and high density lipoprotein were measured. Then, the rats were randomly divided into four groups of 1, 2, 3, and 4 and a high-fat model control group according to the basal blood lipid level, and 6 rats in each group. 1, 2, 3 three experimental groups were given the amino acid composition prepared in Examples 1, 2, and 3, respectively, 4 experimental group was given N-carbamoyl glutamic acid, and the daily dose was N-carbamoylglutamic acid. The samples were 5mg/kg, 50mg/kg, 100mg/kg, 150mg/kg, respectively . The high-fat model group was given distilled water, and each group was fed with high-fat and high-nutrition feed. After 28 days of continuous feeding, the blood samples of the rats were taken for blood lipid levels. The experimental results are as follows: Effects on animal cholesterol: Cholesterol (mmol/L) group of animals
模型对照组 6 1.75 ±0.15 3.54±0.41  Model control group 6 1.75 ±0.15 3.54±0.41
1实验组 6 1.77±0.12 2.91±0.31  1 experimental group 6 1.77±0.12 2.91±0.31
2实验组 6 1.76±0.11 2.75±0.25  2 experimental group 6 1.76 ± 0.11 2.75 ± 0.25
3实验组 6 1.77±0.13 2.89±0.29  3 experimental group 6 1.77±0.13 2.89±0.29
4实验组 6 1.80±0.16 3.76±0.37 对于动物甘 3三酯的影响 甘油三酯 （mmol/L)  4 Experimental group 6 1.80±0.16 3.76±0.37 Effect on animal triglyceride Triglyceride (mmol/L)
组别 动物数 实验前 实验后  Group number of animals before experiment
模型对照组 6 1.08±0.07 3.63±0.54  Model control group 6 1.08±0.07 3.63±0.54
1实验组 6 1.07±0.05 3.04 + 0.42  1 experimental group 6 1.07±0.05 3.04 + 0.42
2实验组 6 1.04±0.06 2.89±0.37  2 experimental group 6 1.04 ± 0.06 2.89 ± 0.37
3实验组 6 1.05±0.04 3.02±0.39  3 experimental group 6 1.05±0.04 3.02±0.39
4实验组 6 1.05±0.05 3.62±0.52 对动物高密度脂蛋白的影响  4Experimental group 6 1.05±0.05 3.62±0.52 Effect on high density lipoprotein in animals
高密度脂蛋白 （mmol/L)  High density lipoprotein (mmol/L)
组别 动物数 实验前 实验后  Group number of animals before experiment
模型对照组 6 0.81士0.09 0.73 ±0.08  Model control group 6 0.81 ± 0.09 0.73 ± 0.08
1实验组 6 0.77±0.05 0.74 ±0.06  1 experimental group 6 0.77±0.05 0.74 ±0.06
2实验组 6 0.79±0.06 0.80±0.07  2 experimental group 6 0.79±0.06 0.80±0.07
3实验组 6 0.75±0.04 0.72 ±0.06  3 experimental group 6 0.75±0.04 0.72 ±0.06
4实验组 6 0.78±0.05 0.76±0.05 对于实验结果的统计分析表明， 单独的 N-氨甲酰谷氨酸没有明显的降 脂作用， 而实施例 1、 2、 3所制得的氨基酸组合物均有明显的降血脂的作 (P值均大于 0.05)，其中以实施例 2所制得的氨基酸组合物的降血脂作用 为明显。 实施例 9  4 Experimental group 6 0.78 ± 0.05 0.76 ± 0.05 Statistical analysis of the experimental results showed that N-carbamoyl glutamic acid alone had no significant lipid-lowering effect, while the amino acid compositions prepared in Examples 1, 2, and 3 There were significant hypolipidemic effects (P values greater than 0.05), wherein the hypolipidemic effect of the amino acid composition prepared in Example 2 was evident. Example 9
促进肌肉生长的作用 Promote muscle growth
实验动物： SD大鼠 80-100g 实验方法： 将 30只大鼠随机分为 1、 2、 3、 4实验组及正常对照组， 每组 6 只大鼠， 1、 2、 3 实验组分别给予实施例 1， 2， 3 制得的氨基酸组合物， 4 实验组给 N-氨甲酰谷氨酸，每天的剂量以 N-氨甲酰谷氨酸计分别为 5mg/kg， 50mg/kg、 100mg/kg和 150mg/kg。 以正常饲料喂养 4周。 观察大鼠的体重变 化， 同时对于大鼠的肌肉组织成份进行分析。 体重 (g) Experimental animals: SD rats 80-100g Experimental methods: 30 rats were randomly divided into 1, 2, 3, 4 experimental group and normal control group, 6 rats in each group. 1, 2, 3 experimental groups were given respectively in Examples 1, 2, 3 The amino acid composition, 4 experimental group gave N-carbamoylglutamic acid, and the daily dose was 5 mg/kg, 50 mg/kg, 100 mg/kg and 150 mg/kg, respectively, based on N-carbamoylglutamic acid. Feeded on normal feed for 4 weeks. The changes in body weight of the rats were observed, and the muscle tissue components of the rats were analyzed. Weight (g)
组别 动物数 初始值 终末值 正常对照组 95.7 ± 5.2 270.1 ± 16.8 1实验组 92.2 ±4.8 295.5 ± 18.7 Group Animal number Initial value End value Normal control group 95.7 ± 5.2 270.1 ± 16.8 1 Experimental group 92.2 ± 4.8 295.5 ± 18.7
2实验组 97.3 ±4.9 297.8 ± 17.9 3实验组 93.5 ±4.5 304.7 ± 19.8 4实验组 94.25士5.6 302.85士18.7 对实验结果的统计分析表明， 1、 2、 3、 4 实验组与正常对照组相比， 动 物的体重都有增加， 其中尤其以 3实验组增加体重最为明显。 此外对于大鼠 肌肉组织成分的分析表明， 大鼠体重的增加主要是由于肌肉组织中组织蛋白 的增生所造成的， 而非脂肪组织的过量增长所引起的。这就表明了 N-氨甲酰 谷氨酸以及实施例 1、 2、 3制备的氨基酸组合物均有促进动物肌肉组织生长 的作用， 其中以实施例 3所制备的氨基酸组合物的促生长作用组为明显 ( 2 Experimental group 97.3 ± 4.9 297.8 ± 17.9 3 Experimental group 93.5 ± 4.5 304.7 ± 19.8 4 Experimental group 94.25 5.6 302.85 ± 18.7 Statistical analysis of the experimental results showed that the 1, 2, 3, 4 experimental group compared with the normal control group Animals have increased their body weight, especially in the 3 experimental group. In addition, analysis of the composition of rat muscle tissue showed that the increase in body weight of rats was mainly caused by the proliferation of tissue proteins in muscle tissue, rather than the excessive growth of adipose tissue. This indicates that both N-carbamoylglutamic acid and the amino acid compositions prepared in Examples 1, 2, and 3 have an effect of promoting the growth of muscle tissue of an animal, wherein the growth promoting effect of the amino acid composition prepared in Example 3 Group is obvious (

Claims

酉匕曰 权利要求 酉匕曰claims
1、 N-氨甲酰谷氨酸、 其盐或其酯在制备护肝、 促肌肉生长保健品中的 应用。 1. The use of N-carbamoylglutamic acid, a salt thereof or an ester thereof for preparing a liver-protecting and muscle-promoting health care product.
2、 根据权利要求 1所述的应用， 其特征在于， 所述 N-氨甲酰谷氨酸为 L-型。  The use according to claim 1, wherein the N-carbamoylglutamic acid is L-form.
3、 根据权利要求 1所述的应用， 其特征在于， 所述 N-氨甲酰谷氨酸的 盐是无机酸盐、 有机酸盐、 金属盐、 铵盐、 有机铵盐或氨基酸盐。  The use according to claim 1, wherein the salt of N-carbamoylglutamic acid is a mineral acid salt, an organic acid salt, a metal salt, an ammonium salt, an organic ammonium salt or an amino acid salt.
4、 根据权利要求 1所述的应用， 其特征在于， 所述 N-氨甲酰谷氨酸的 的酯是低级醇酯。  4. Use according to claim 1, characterized in that the ester of N-carbamoylglutamic acid is a lower alcohol ester.
5、根据权利要求 4所述的应用， 其特征在于， 所述低级醇酯为甲酯或乙  5. The use according to claim 4, wherein the lower alcohol ester is methyl ester or ethyl
6、 一种具有护肝、 促肌肉生长作用的氨基酸组合物， 其特征在于， 按重 ：百分含量计， 该氨基酸组合物由下列组分组成： 6. An amino acid composition having liver protection and muscle growth promoting action, characterized in that the amino acid composition is composed of the following components in terms of weight: percentage:
N-氨甲酰谷氨酸、 其盐或其酯 0.92~18.00%; N-carbamoylglutamic acid, its salt or its ester 0.92~18.00% ;
0.80-17.00%；  0.80-17.00%;
盐酸吡哆辛 0.10-1.70%；  Pyridoxine hydrochloride 0.10-1.70%;
甘氨酸 4.50-32.00%；  Glycine 4.50-32.00%;
含锌化合物 1.35-2.70%；  Zinc-containing compound 1.35-2.70%;
烟酰胺 3.50-7.50%；  Nicotinamide 3.50-7.50%;
牛磺酸 1.20-37.00%；  Taurine 1.20-37.00%;
琥珀酸  Succinic acid
7、 根据权利要求 6所述的具有护肝、 促肌肉生长作用的氨基酸组合物， 其特征在于， 所述含锌化合物为二水合醋酸锌或柠檬酸锌。  The amino acid composition having liver protection and muscle growth promoting action according to claim 6, wherein the zinc-containing compound is zinc acetate dihydrate or zinc citrate.
8、 根据权利要求 6所述的具有护肝、 促肌肉生长作用的氨基酸组合物， 其特征在于，所述 N-氨甲酰谷氨酸的盐、精氨酸的盐是无机酸盐、有机酸盐、 金属盐、 铵盐、 有机铵盐或氨基酸盐。 8. The amino acid composition having liver protection and muscle growth promoting action according to claim 6, It is characterized in that the salt of N-carbamoylglutamic acid or the salt of arginine is a mineral acid salt, an organic acid salt, a metal salt, an ammonium salt, an organic ammonium salt or an amino acid salt.
9、 根据权利要求 6所述的具有护肝、 促肌肉生长作用的氨基酸组合物， 其特征在于， 所述 N-氨甲酰谷氨酸的酯、 精氨酸的酯是低级醇酯， 优选甲酯 或乙酯。  The amino acid composition having a liver-protecting and muscle-promoting action according to claim 6, wherein the ester of N-carbamoylglutamic acid and the ester of arginine are lower alcohol esters, preferably Methyl or ethyl ester.
10、 一种具有护肝、 促肌肉生长作用的保健品， 其特征在于包含权利要 求 6~9任一项所述的具有护肝、 促肌肉生长作用的氨基酸组合物和药学上可 接受的载体。  A health care product having a liver-protecting and muscle-promoting action, comprising the amino acid composition having liver protection and muscle growth promoting action according to any one of claims 6 to 9, and a pharmaceutically acceptable carrier .
PCT/CN2010/000944 2010-06-24 2010-06-24 Use of n-carbamoyl glutamic acid, salts or esters thereof in manufacture of health care products for protecting liver or promoting muscle growth WO2011160259A1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102718685A (en) * 2012-06-01 2012-10-10 广州九益生物技术有限公司 Preparation method and application of N-carbamyl-L-glutamic acid manganese complex
CN105820060A (en) * 2016-03-28 2016-08-03 广州英赛特生物技术有限公司 Grain and meat silicate and application thereof to preparation of animal feed additive

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Publication number Priority date Publication date Assignee Title
GB1112347A (en) * 1965-08-20 1968-05-01 Pierre Wirth Salts of organic bases with n-carbamyl-l-glutamic acid

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1112347A (en) * 1965-08-20 1968-05-01 Pierre Wirth Salts of organic bases with n-carbamyl-l-glutamic acid

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102718685A (en) * 2012-06-01 2012-10-10 广州九益生物技术有限公司 Preparation method and application of N-carbamyl-L-glutamic acid manganese complex
CN105820060A (en) * 2016-03-28 2016-08-03 广州英赛特生物技术有限公司 Grain and meat silicate and application thereof to preparation of animal feed additive
CN105820060B (en) * 2016-03-28 2018-02-23 广州英赛特生物技术有限公司 Paddy carnic acid salt and its application in additive for animal feed is prepared

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