CN101437511A - Agent for preventing liver disease - Google Patents
Agent for preventing liver disease Download PDFInfo
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- CN101437511A CN101437511A CNA2007800166823A CN200780016682A CN101437511A CN 101437511 A CN101437511 A CN 101437511A CN A2007800166823 A CNA2007800166823 A CN A2007800166823A CN 200780016682 A CN200780016682 A CN 200780016682A CN 101437511 A CN101437511 A CN 101437511A
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- hydroxyproline
- acylate
- proline
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- hydroxyl
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
Disclosed are an agent for preventing a liver disease, an agent for preventing an alcoholic liver disease, and the like. Specifically, disclosed is an agent for preventing a liver disease, comprising hydroxyproline or an N-acylated hydroxyproline or a salt thereof as an active ingredient.
Description
Technical field
The present invention relates to contain the N-acylate of hydroxyproline or hydroxyproline or its salt agent for preventing liver disease as effective ingredient.
Background technology
Liver is a kind of important internal organs, is bearing metabolism adjusting and storage sugar, protein and lipid and the various functions such as decomposition and the unwanted material of detoxifcation body as three big nutrients.The excessive picked-up of ethanol, viral infection, unbalanced dietary habit, pressure and smoking etc. can cause that these functions are subjected to acute or chronic injury, and when this lesion development, for example diseases such as acute hepatitis, chronic hepatitis, liver cirrhosis, alcoholic fatty liver, Type B viral hepatitis, hepatocarcinoma can appear.
When hepatocyte when due to illness poison, ethanol etc. sustain damage, aspartate aminotransferase in the cell (is also referred to as glutamic oxaloacetic transaminase, GOT, below brief note is for GOT) and alanine aminotransferase (be also referred to as glutamate pyruvate transaminase, below brief note is for GPT) wait enzyme in blood, to occur, therefore represent the numerical value rising of these enzymatic activitys.Therefore, the index of the active function damage as the expression liver of GOT in the blood and GPT and known.
As the medicament that can be used in prevention or treatment liver dysfunction, antiviral agent such as known for example acyclovir, immunosuppressant (with reference to non-patent literature 1), glutathion (with reference to non-patent literature 2) etc.
And, knownly can suppress by the hepatic injury (with reference to patent documentation 1) of tetrachloro-methane induction, can suppress by the inductive hepatic injury of galactosamine (with reference to patent documentation 2) by using the L-proline by using the L-proline.Can prevent alcoholic liver injury (with reference to patent documentation 3) by the picked-up proline, but in the test example, not demonstrate the rising that suppresses serum GPT, but the result that concentration of alcohol rises in the blood occur promoting.
And, the carboxyl condensation of the amino of known hydroxyproline and alpha-amino acid compound and the hydroxyproline derivant that obtains suppresses by carbon tetrachloride or isothiocyanic acid α-Nai Zhi (α-naphthylisothiocyanate) inductive hepatic injury (with reference to patent documentation 4).
But, also and do not know hydroxyproline or make the amino of hydroxyproline and the carboxyl condensation of fatty acid and the N-acylate that obtains to the effect of liver function.
Patent documentation 1: Japanese kokai publication hei 10-298075 communique
Patent documentation 2: Japanese kokai publication hei 8-208472 communique
Patent documentation 3: Japanese kokai publication hei 6-116144 communique
Patent documentation 4: Japanese kokai publication hei 11-21295 communique
Non-patent literature 1: " medical science あ ゆ body (progress of medical science) ", doctor's tooth medicine is published, and 1994, the 171st volume, No. 14, p.957～1158
Non-patent literature 2: " the white Quality nucleic acid of egg ferment (protein nucleic acid enzyme) ", upright altogether the publication, 1988, the 33rd volume, No. 9, p.1625～1631
Summary of the invention
The object of the present invention is to provide agent for preventing liver disease.
The present invention relates to following (1)～(9).
(1) a kind of agent for preventing liver disease contains the N-acylate of hydroxyproline or hydroxyproline or its salt as effective ingredient.
(2) a kind of alcoholic liver injury inhibitor contains the N-acylate of hydroxyproline or hydroxyproline or its salt as effective ingredient.
(3) as above-mentioned (1) or (2) described preparation, wherein, the N-acylate of hydroxyproline is N-acetylate, N-third acylate, N-Butyrylation thing or N-isobutyl acylate.
(4) a kind of hepatic injury inhibition method is characterized in that, the hydroxyproline of effective dose or N-acylate or its salt of hydroxyproline are applied to the object that needs.
(5) a kind of alcoholic liver injury inhibition method is characterized in that, the hydroxyproline of effective dose or N-acylate or its salt of hydroxyproline are applied to the object that needs.
(6) as above-mentioned (4) or (5) described method, wherein, the N-acylate of hydroxyproline is N-acetylate, N-third acylate, N-Butyrylation thing or N-isobutyl acylate.
(7) the N-acylate of hydroxyproline or hydroxyproline or its salt application in making agent for preventing liver disease.
(8) the N-acylate of hydroxyproline or hydroxyproline or its salt application in making the alcoholic liver injury inhibitor.
(9) as above-mentioned (7) or (8) described application, wherein, the N-acylate of hydroxyproline is N-acetylate, N-third acylate, N-Butyrylation thing or N-isobutyl acylate.
The invention effect
According to the present invention, can provide agent for preventing liver disease safely and effectively.
Description of drawings
Fig. 1 illustrates the figure that utilizes hydroxyproline and acetyl hydroxyproline to suppress the effect of alcoholic liver injury.Represent to give the test group that corn starch adds feedstuff for the 1st group, represent to give the test group that the L-proline adds feedstuff for the 2nd group, represent to give the test group that the L-hydroxyproline adds feedstuff for the 3rd group, represent to give the test group that the acetyl hydroxyproline adds feedstuff for the 4th group.The longitudinal axis of figure represents GPT concentration in the 1st group the blood is made as relative value's (mean+SD) of GPT concentration in the blood of respectively organizing at 100 o'clock.
The specific embodiment
The hydroxyproline that can use among the present invention can be any stereoisomer of hydroxyproline.That is, the position of D type or L type, hydroxyl can be 3 or 4 and its stereoisomer can be cis or trans because the proline of hydroxyproline can be, thereby has 8 kinds of stereoisomers, and any chemical compound all can be used in the present invention.
As concrete hydroxyproline, can list suitable-4-hydroxyl-L-proline, suitable-4-hydroxyl-D-proline, suitable-3-hydroxyl-L-proline, suitable-3-hydroxyl-D-proline, anti--4-hydroxyl-L-proline, anti--4-hydroxyl-D-proline, anti--3-hydroxyl-L-proline and anti--3-hydroxyl-D-proline.
Hydroxyproline is a seed amino acid that is widespread in nature as the formation aminoacid of main composition aminoacid ingredient in the collagen protein or elastin laminin, for example, after can carrying out acid hydrolysis by collagen protein, utilize well-established law to purify and make animal origins such as pig or cattle.
Instead-4-hydroxyl-L-proline can belong to or refer to that sporangiocyst bacterium (Dactylosporangium) belongs to separates the proline-4-position hydroxylase (Japanese kokai publication hei 7-313179) that obtains and make by using by amycolatosis (Amycolatopsis).And, suitable-3-hydroxyl-L-proline can be made (biological industry (バ イ オ イ Application ダ ス ト リ-) by using proline 3 position hydroxylase (Japanese kokai publication hei 7-322885) that is obtained by the separation of streptomycete (Streptomyces) genus, 14 volumes, No. 31,1997).
Use the superior in quality of hydroxyproline that the enzyme in mentioned microorganism source makes, be more preferably as the hydroxyproline that uses among the present invention.
As the N-acylate of the hydroxyproline that can use in the present invention, can list the N-acylate of the stereoisomer of above-mentioned various hydroxyprolines.As the acyl group of this N-acylate, can be any in the saturated or unsaturated acyl group of straight or branched, but the saturated acyl group of preferred straight or branched.As the carbon number of acyl group, preferred carbon number is 1～24, and being more preferably carbon number is 1～12, and preferred especially carbon number is 1～6.As acyl group; for example can list formoxyl, acetyl group, propiono, bytyry, isobutyryl, valeryl, pivaloyl group, caproyl, heptanoyl group, caprylyl, pelargonyl group, capryl, undecanoyl, lauroyl etc., preferred especially acetyl group, propiono, bytyry and isobutyryl.
The N-acylate of the hydroxyproline that can use in the present invention can be prepared by known method.For example; the N-acylate of hydroxyproline can be made by method as described below: using halogenating agents such as thionyl chloride, phosgene is to carry out condensation with above-mentioned hydroxyproline after 1～24 saturated or unsaturated fatty acid changes halogenide such as chloride, bromide into the straight or branched carbon number; perhaps, react with hydroxyproline after fatty acid being changed into anhydride.
As fatty acid, for example can be used alone or in combination fatty acids such as formic acid, acetic acid, propanoic acid, butanoic acid, isopropylformic acid., valeric acid, isovaleric acid, pivalic acid, caproic acid, enanthic acid, sad, n-nonanoic acid, capric acid, hendecanoic acid, dodecylic acid.
Following example shows the method for making the N-acylate of hydroxyproline via carboxylic acid halides.
Can make the N-acylate of hydroxyproline by the following method: fatty acid is scattered in dichloromethane, chloroform, carbon tetrachloride, benzene, dimethylbenzene, the normal hexane equal solvent; add and be equivalent to 1～5 times of normal halogenating agent of fatty acid and make its reaction; obtain fatty acid halide; then; hydroxyproline is dissolved or dispersed in the solvent; and gained solution remained under 5～70 ℃, add simultaneously with respect to 0.3～3.0 times of normal above-mentioned fatty acid halide of hydroxyproline and carry out acylation reaction.
As the solvent that can be used in acylation reaction, can enumerate water outlet, methanol, ethanol, isopropyl alcohol, isobutanol, acetone, toluene, oxolane, ethyl acetate, N, dinethylformamide, dimethyl sulfoxine etc. can be used alone or as a mixture these solvents.When being dissolved or dispersed in hydroxyproline in the solvent, can be as required with respect to alkali dissolutions such as 0.8～2.0 times of normal sodium hydroxide of hydroxyproline, potassium hydroxide or be dispersed in the solvent.
When hope obtains the salt of N-acylate of hydroxyproline; obtain in form can directly purifying, when obtaining under the situation of N-acylate of hydroxyproline with free form with salt; can make its dissolving or be suspended in the appropriate solvent, and add alkali and make it form salt.
Purification can be used for example usual way such as crystallization, chromatography.
As the N-acylate of concrete hydroxyproline, for example can list N-acetyl group-suitable-4-hydroxyl-L-proline; N-acetyl group-suitable-4-hydroxyl-D-proline; N-acetyl group-suitable-3-hydroxyl-L-proline; N-acetyl group-suitable-3-hydroxyl-D-proline; N-acetyl group-anti--4-hydroxyl-L-proline; N-acetyl group-anti--4-hydroxyl-D-proline; N-acetyl group-anti--3-hydroxyl-L-proline; N-acetyl group-anti--3-hydroxyl-D-proline; N-propiono-suitable-4-hydroxyl-L-proline; N-propiono-suitable-4-hydroxyl-D-proline; N-propiono-suitable-3-hydroxyl-L-proline; N-propiono-suitable-3-hydroxyl-D-proline; N-propiono-anti--4-hydroxyl-L-proline; N-propiono-anti--4-hydroxyl-D-proline; N-propiono-anti--3-hydroxyl-L-proline; N-propiono-anti--3-hydroxyl-D-proline; N-bytyry-suitable-4-hydroxyl-L-proline; N-bytyry-suitable-4-hydroxyl-D-proline; N-bytyry-suitable-3-hydroxyl-L-proline; N-bytyry-suitable-3-hydroxyl-D-proline; N-bytyry-anti--4-hydroxyl-L-proline; N-bytyry-anti--4-hydroxyl-D-proline; N-bytyry-anti--3-hydroxyl-L-proline; N-bytyry-anti--3-hydroxyl-D-proline; N-isobutyryl-suitable-4-hydroxyl-L-proline; N-isobutyryl-suitable-4-hydroxyl-D-proline; N-isobutyryl-suitable-3-hydroxyl-L-proline; N-isobutyryl-suitable-3-hydroxyl-D-proline; N-isobutyryl-anti--4-hydroxyl-L-proline; N-isobutyryl-anti--4-hydroxyl-D-proline; N-isobutyryl-anti--3-hydroxyl-L-proline and N-isobutyryl-anti--3-hydroxyl-D-proline etc.
Salt as the N-acylate of hydroxyproline or hydroxyproline can list acid-addition salts, slaine, ammonium salt, organic amine addition salts and amino acid addition salt etc.
As acid-addition salts, can list inorganic acid salts such as hydrochlorate, sulfate, nitrate, phosphate, acylates such as acetate, maleate, fumarate, malate, lactate, alpha-ketoglutarate, gluconate, caprylate, Orotate.
As slaine, can list alkali metal salts such as sodium salt, potassium salt, alkali salts such as magnesium salt, calcium salt, aluminum salt, zinc salt etc.
As ammonium salt, can list the salt of ammonium, tetramethyl-ammonium etc.
As the organic amine addition salts, can list the salt of morpholine, piperidines etc.
As amino acid addition salt, can list the salt of glycine, phenylalanine, aspartic acid, glutamic acid etc.
The inhibition of hepatic injury comprises prevention or alleviates the effect etc. of the liver function that effect, recovery or the treatment of liver dysfunction sustain damage.
The said liver function of the present invention is meant the repertoire that liver has, and is not particularly limited.As concrete liver function, for example can enumerate blood storage (adjusting of circulating load etc.), the processing of haemachrome (the processing discharge of hemoglobin etc.), biliary generation, the liver sausage circulation of bile pigments, plasma proteins (acute phase protein, albumin, thrombin, steroid binding protein, other hormone is conjugated protein etc.) synthetic blood and the circulation function of waiting, nutrient and vitamin (glucose and other saccharide, aminoacid, lipid or fatty acid, cholesterol, lipoprotein, fatsoluble vitamin, the metabolic function of nutrients such as metabolism water soluble vitamins etc.), various material (toxin, steroidal compounds such as estrogen or androsterone, other hormone etc.) detoxifcation or decomposition functions such as inactivation, and immunologic function etc. (" physiology's prospect ", former book 19 editions (putting down on March 31st, 12), " new clinical nutriology " revised the 3rd edition (on May 20th, 2000)).These liver functions all are subjected to by the caused damage of ethanol.
By agent for preventing liver disease of the present invention is applied to the human or animal that liver function has had damage, can improve liver dysfunction.And, by agent for preventing liver disease of the present invention being applied to the unconspicuous human or animal of liver dysfunction, can the prevention of liver damage.
As agent for preventing liver disease of the present invention, can directly use N-acylate or its salt of hydroxyproline or hydroxyproline, but various preparations preferably are provided usually.
Preparation contains the N-acylate of hydroxyproline or hydroxyproline or its salt as effective ingredient, is useful on the effective ingredient of other treatment arbitrarily but can also contain.And these preparations can be by mixing effective ingredient with acceptable one or more carrier on the pharmacology, and utilize in the technical field of galenic pharmacy known any means to make.
The administering mode of preparation preferably uses effective and efficient manner of when treatment, can enumerate oral administration or non-oral administrations such as intravenous, intraperitoneal or subcutaneous administration for example, but the preferred oral administration.
Dosage form as administration, for example can be oral formulations such as tablet, powder, granule, pill, suspensoid, Emulsion, leaching agent, decoct, capsule, syrup, liquid agent, elixir, extractum, tincture, fluid extract, any in the non-oral formulations such as injection, drop, ointment, suppository, but preferably use oral formulations.
When oral formulations is carried out preparation, can use additives such as excipient, binding agent, disintegrating agent, lubricant, dispersant, suspending agent, emulsifying agent, diluent, buffer agent, antioxidant, antibacterial.The such liquid preparation of for example syrup that is fit to oral administration can make saccharides such as water, sucrose, sorbitol, fructose, glycols such as Polyethylene Glycol, propylene glycol, Oleum sesami, olive oil, Semen sojae atricolor wet goods oils, antiseptic such as parabens, perfumeries such as strawberry flavor, Herba Menthae are made.
And tablet, powder and granule etc. can wait by plasticizers such as surfactants such as binding agents such as lubricants such as disintegrating agents such as excipient, starch, sodium alginate, magnesium stearate, Pulvis Talci, polyvinyl alcohol, hydroxypropyl cellulose, gelatin, fatty acid ester, glycerol such as interpolation lactose, glucose, sucrose, mannitols and carry out preparation.
In addition, be suitable in the preparation of oral administration, can add the additive that can be used in the diet product usually, for example sweeting agent, coloring agent, antistaling agent, tackify stabilizing agent, antioxidant, color-fixing agent, bleach, antifungus agent, gum base, bitters, enzyme, polishing material, acidic flavoring agent, flavoring agent, emulsifying agent, hardening agent, manufacturing agent, spice, spice extract etc.
The preparation that is suitable for oral administration can be form itself, also can be forms such as powdered food product, laminar food, bottled food, canned food, high pressure sterilization canned food, capsule-shaped food, sheet-like food, fluid food, beverage for example.And the diet product such as the health food that is used to suppress hepatic injury, functional food, nutrient supplement food, specific food for health care that also can be used as use.
The for example injection that is suitable for non-oral administration preferably oozes with blood of receptor etc., is made of the sterilization aqueous agent that contains lysine and citric acid.For example, under the situation of injection, the manufacturing injection solutions such as carrier that use the mixture by saline solution, glucose solution or saline and glucose solution to constitute.
And, in these non-oral Preparations, also can add the auxiliary element that is selected from one or more in illustrative diluent, antiseptic, perfumery, excipient, disintegrating agent, lubricant, binding agent, surfactant, the plasticizer etc. in the oral formulations.
The N-acylate of hydroxyproline in the preparation of the present invention or hydroxyproline or the concentration of its salt are according to the kind of preparation, suitably select by using the effect that this reagent expects; for example under the situation of oral formulations; N-acylate or its salt as hydroxyproline or hydroxyproline; be generally 0.1～90 weight %; be preferably 0.5～70 weight %, be preferably 1～50 weight % especially.
The dosage of agent for preventing liver disease of the present invention is according to age of administering mode, the person of being applied, body weight etc. and different; but under case of oral administration; N-acylate or its salt as hydroxyproline or hydroxyproline; for the adult; be generally 100～10000mg every day; be preferably 100～2000mg, be preferably 200～1000mg especially, 1 time on the 1st or be divided into multiple dosing.The administration cycle is not particularly limited, but is generally 1 day～1 year, is preferably 1 week～3 month.
In addition, oral formulations of the present invention is not only for the people, also can use for the animal beyond the people (below, abbreviate the non-human animal as).
As the non-human animal, can list people such as mammals, birds, reptile class, amphibian, Fish animal in addition.
Dosage when being applied to the non-human animal is according to age of animal, kind etc. and different; but as N-acylate or its salt of hydroxyproline or hydroxyproline, 1 time on the 1st or multiple dosing are so that per 1 kilogram of body weight is generally 2～20mg 1 time; be preferably 2～40mg, be preferably 4～20mg especially.The administration cycle is not particularly limited, but is generally 1 day～1 year, is preferably 1 week～3 month.
The test example of the N-acylate of research hydroxyproline or hydroxyproline to the inhibition effect of alcoholic liver injury below is shown.
Test example 1
Using SD in the test is female rats (in 7～9 ages in week, body weight 150～220g is available from Japanese エ ス エ Le シ-company).The raising condition is 22 ± 2 ℃ of room temperatures, humidity 35 ± 15% and makes it freely absorb feedstuff and water.
Each test group is made of 6 rats, raise the 1st group rat 13 days with the commercial powder feedstuff CE-2 that is added with 5 weight % corn starchs (Japanese Network レ ア corporate system), raise the 2nd group rat 13 days with the CE-2 that is added with 5 weight %L-proline (consonance Kyowa Hakko system), raise the 3rd group rat 13 days with the CE-2 that is added with 5 weight %L-hydroxyprolines (consonance Kyowa Hakko system), raise the 4th group rat 13 days with the CE-2 that is added with 5 weight % acetyl hydroxyprolines (consonance Kyowa Hakko system).
The 14th day with per unit body weight 4g/kg orally give 40% ethanol water, after 6 hours with per unit body weight 5mg/kg intravenous injection lipopolysaccharide (シ グ マ corporate system).The injection lipopolysaccharide after 22 hours under the abdomen large artery trunks get blood, measure in the blood GPT concentration as the index of hepatic injury.GPT concentration is represented with the relative value of GPT concentration in the 1st group the blood as 100 o'clock in the blood of each group.In addition, the normal value of GPT concentration is 5～20IU/L in the blood, and is relative therewith, and GPT concentration is about 300IU/L in the 1st group the blood.
Show the result in Fig. 1.GPT is identical with the 1st group degree in the blood in the 2nd group, and is relative therewith, and GPT concentration reduces in the blood in the 3rd group and the 4th group.
By above result as can be known, proline does not demonstrate the inhibition effect of alcoholic liver injury, and is relative therewith, and hydroxyproline and acetyl hydroxyproline are obvious to the inhibition effect of alcoholic liver injury.
Below show embodiments of the invention.
Embodiment 1
Contain the manufacturing of the tablet of hydroxyproline
Manufacturing contains instead according to well-established law-tablet of 4-hydroxyl-L-proline.That is,, and place single punch tablet machine to carry out tabletting this mixture, obtain the tablet of diameter 5mm, weight 15mg following each composition mix homogeneously.
[table 1]
Become component (g)
Instead-4-hydroxyl-L-proline 10.0
Lactose 90.0
Dried corn starch 2.0
Pulvis Talci 1.8
Magnesium stearate 0.2
Embodiment 2
Contain the manufacturing of the granule of hydroxyproline
Tablet pulverizing, granulation, the granulate that will be obtained by embodiment 1 obtain 20-50 purpose granule.
Embodiment 3
Contain the manufacturing of the health beverage of hydroxyproline
Then add pure water and make the health beverage that contains anti--4-hydroxyl-L-proline by following each composition being stirred and dissolving so that total amount is 1000ml.In addition, an amount of in the following compositions is meant the amount that can use in the manufacturing of common health beverage for spice, pigment, be meant the composition that adds other for pure water after, be the amount that 1000ml needs in order to make total amount.
[table 2]
Become component (g)
Instead-4-hydroxyl-L-proline 5.0
Sodium benzoate 1.0
Fructose 10.0
Spice is an amount of
Pigment is an amount of
Pure water is an amount of
Embodiment 4
Contain the manufacturing of the sugar of N-acetyl hydroxyproline.
By the well-established law manufacturing by following each become the sugar be grouped into, contain N-acetyl group-anti--4-hydroxyl-L-proline.
[table 3]
Become component (g)
N-acetyl group-anti--4-hydroxyl-L-proline 1.00
Powder sorbitol 98.75
Spice 0.20
Sorbitol crystal seed (sorbitol seed) 0.05
Embodiment 5
Contain of the manufacturing of the animal of hydroxyproline with combination agent
Use combination agent by the well-established law manufacturing by following each animal that become to be grouped into, that contain anti--4-hydroxyl-L-proline.
[table 4]
Become component (g)
Instead-4-hydroxyl-L-proline 1.0
Adeps Sus domestica 5.0
Semen Maydis oil 1.0
Sucrose 20.0
Cellulose 5.0
Choline chloride 0.2
Vitamin mixtures 1.0
Mineral mixture 3.5
Corn starch 44.3
Utilize possibility on the industry
According to the present invention, can provide the N-acylate that contains hydroxyproline or hydroxyproline or its Salt is as the agent for preventing liver disease of active ingredient.
Claims (9)
1. agent for preventing liver disease contains the N-acylate of hydroxyproline or hydroxyproline or its salt as effective ingredient.
2. alcoholic liver injury inhibitor contains the N-acylate of hydroxyproline or hydroxyproline or its salt as effective ingredient.
3. preparation as claimed in claim 1 or 2, wherein, the N-acylate of hydroxyproline is N-acetylate, N-third acylate, N-Butyrylation thing or N-isobutyl acylate.
4. a hepatic injury inhibition method is characterized in that, the hydroxyproline of effective dose or N-acylate or its salt of hydroxyproline are applied to the object that needs.
5. an alcoholic liver injury inhibition method is characterized in that, the hydroxyproline of effective dose or N-acylate or its salt of hydroxyproline are applied to the object that needs.
6. as claim 4 or 5 described methods, wherein, the N-acylate of hydroxyproline is N-acetylate, N-third acylate, N-Butyrylation thing or N-isobutyl acylate.
7. the N-acylate of hydroxyproline or hydroxyproline or its salt application in making agent for preventing liver disease.
8. the N-acylate of hydroxyproline or hydroxyproline or its salt application in making the alcoholic liver injury inhibitor.
9. as claim 7 or 8 described application, wherein, the N-acylate of hydroxyproline is N-acetylate, N-third acylate, N-Butyrylation thing or N-isobutyl acylate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006130557 | 2006-05-09 | ||
| JP130557/2006 | 2006-05-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101437511A true CN101437511A (en) | 2009-05-20 |
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ID=38667833
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800166823A Pending CN101437511A (en) | 2006-05-09 | 2007-05-09 | Agent for preventing liver disease |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPWO2007129725A1 (en) |
| CN (1) | CN101437511A (en) |
| WO (1) | WO2007129725A1 (en) |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3479986B2 (en) * | 1992-10-07 | 2003-12-15 | 大正製薬株式会社 | Composition for preventing alcoholic liver injury |
| JPH08208472A (en) * | 1994-12-07 | 1996-08-13 | Res Dev Corp Of Japan | Antihepatitis agent |
| JPH10298075A (en) * | 1997-04-25 | 1998-11-10 | Eisai Co Ltd | Preventive and therapeutic agent for hepatopathy |
| DE69838303T2 (en) * | 1998-03-16 | 2008-06-26 | Japan Bioproducts Ind. Co., Ltd. | DERIVATIVES HYDROXYPROLINE |
| US20040048772A1 (en) * | 2001-01-05 | 2004-03-11 | Ryusuke Nakagiri | Preventives for arthritis |
| WO2004039368A1 (en) * | 2002-11-01 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd. | Peroral preparation for prevention of or treatment for atopic dermatitis |
| US7485662B2 (en) * | 2003-03-19 | 2009-02-03 | Kyowa Hakko Kogyo Co., Ltd. | Therapeutic agent for diabetes mellitus |
| EP1607386A1 (en) * | 2003-03-26 | 2005-12-21 | Kyowa Hakko Kogyo Co., Ltd. | Lipid metabolism improving agent |
| KR20050106528A (en) * | 2003-03-28 | 2005-11-09 | 교와 핫꼬 고교 가부시끼가이샤 | Anti-obesity agent |
| EP1795191A4 (en) * | 2004-09-21 | 2007-12-19 | Kyowa Hakko Kogyo Kk | Oral pharmaceutical for dry skin prevention or remedy |
-
2007
- 2007-05-09 WO PCT/JP2007/059574 patent/WO2007129725A1/en active Application Filing
- 2007-05-09 JP JP2008514505A patent/JPWO2007129725A1/en not_active Withdrawn
- 2007-05-09 CN CNA2007800166823A patent/CN101437511A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007129725A1 (en) | 2007-11-15 |
| JPWO2007129725A1 (en) | 2009-09-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20090520 |