WO2002074303A1 - Compositions d'acides amines pour ameliorer l'insuffisance renale - Google Patents

Compositions d'acides amines pour ameliorer l'insuffisance renale Download PDF

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Publication number
WO2002074303A1
WO2002074303A1 PCT/JP2002/002501 JP0202501W WO02074303A1 WO 2002074303 A1 WO2002074303 A1 WO 2002074303A1 JP 0202501 W JP0202501 W JP 0202501W WO 02074303 A1 WO02074303 A1 WO 02074303A1
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WO
WIPO (PCT)
Prior art keywords
amino acid
mol
renal dysfunction
moles
acid composition
Prior art date
Application number
PCT/JP2002/002501
Other languages
English (en)
Japanese (ja)
Inventor
Takashi Abe
Hiroshi Tsuchita
Original Assignee
Riken
Meiji Dairies Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Riken, Meiji Dairies Corporation filed Critical Riken
Publication of WO2002074303A1 publication Critical patent/WO2002074303A1/fr

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Classifications

    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401—Proline; Derivatives thereof, e.g. captopril
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys

Definitions

  • the present invention relates to an amino acid composition and an amino acid composition solution having a remarkable ameliorating effect on renal dysfunction, and more particularly to a patient with renal dysfunction contained in saliva secreted by a hornet (Vespa) larva.
  • the present invention relates to an amino acid composition and an amino acid composition solution that can be effectively administered to an animal.
  • the present inventors have heretofore clarified the composition of the amino acid composition contained in the saliva secreted by the larvae of the larva of Poa annua, and have been studying its use.
  • the amino acid composition designated as VAAM exhibited a motor function redaction (Patent No. 2518692). Includes sustained muscle strength, nourishment, nourishment, and recovery from fatigue.
  • the kidney a type of H storage device, has the function of filtering out urine components in blood and excreting it outside the body.
  • the kidney which plays such a role, may overload and suffer from renal insufficiency, including renal cancer, when drinking, smoking, staying up late, etc.
  • an object of the present invention is to provide an amino acid composition and an amino acid composition solution having a remarkable renal dysfunction-improving activity and having substantially no side effects.
  • the present invention is characterized in that it comprises threonine, proline, glycine, norin, isoleucine, leucine, thioxacin, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, tributofan, histidine and arginine. It is an amino acid composition for relieving renal dysfunction, and an amino acid composition obtained by removing tributophan from such a composition also has an effect of improving renal dysfunction. Further, the present invention includes an amino acid composition solution, preferably a solution, having substantially the same composition as these compositions in the liquid phase. Each amino acid has a specific preferred ratio of H bonds.
  • VAAM has a motility-enhancing effect as an apparent mechanism of action and enhances lipid metabolism.
  • the present inventors have elucidated in detail whether or not such a motility male action by VA AM effectively acts on improvement of other diseases that are not directly linked to a motility male action. investigated.
  • the kidneys have the same functions as described above, especially when performing intense exercise for a long time, and have a close relationship with the regulation of blood pressure and other circulatory functions and the discharge of waste products produced by exercise. Enhancement is integral to the function of total rise: 3 ⁇ 4t.
  • Enhancement is integral to the function of total rise: 3 ⁇ 4t.
  • alcohol is consumed excessively, there is a tendency for the accumulation of aging in the kidneys, and renal dysfunction may occur if the function is not properly enhanced.
  • renal dysfunction may be incomplete and unrecoverable.
  • the present inventors have proposed to administer a VAAM having a specific composition (having a composition different from that of a known VAAM) to such a patient having renal dysfunction or to a healthy subject before renal dysfunction appears.
  • a VAAM having a specific composition having a composition different from that of a known VAAM
  • they have found that the renal dysfunction is improved or that the occurrence of renal dysfunction can be suppressed, and the present invention has been achieved.
  • the first depleted amino acid according to the present invention contains 17 kinds of amino acids as essential components, and each amino acid is particularly contained in a specific set. desirable. So threonine 2-15 moles, proline 4-30 moles, glycine?
  • valine 4-8 mol isoleucine 3-9 mol, leucine 2-12 mol, tyrosine 1-9 mol, phenylealanine 0.5-5 mol, lysine 5-11 mol, aspartic acid 0.1 ⁇ 5 moles, serine 0.1 ⁇ 5mol, glutamic acid 0.1 ⁇ 4mol, alanine 0.1 ⁇ 12mol, methionine 0.1 ⁇ 5mol, tryptophan 0.1 ⁇ 5mol, histidine 0,1 ⁇ 5 Mol and arginine in a ratio of 0.1 to 5 mol, and may contain amino acids other than the above, water-soluble vitamins, acids such as citric acid, or other small amounts of additives. good.
  • the second amino acid composition according to the present invention contains 16 kinds of amino acids as an essential component in a specific composition ratio, and a thread obtained by removing tributophan from the amino acid composition of the first invention.
  • This tributophan-free amino acid composition also has the same or slightly inferior renal dysfunction as the first invention.
  • Each amino acid is L-amino acid.
  • the amino acid composition and the solution thereof according to the first and second inventions have a lower urea nitrogen concentration, which is an index for renal dysfunction, as compared to other amino acid exfoliated substances, and further have acute poisoning. Both mortality and knockdown rates are low, and the use of this amino acid composition makes it difficult to observe renal function and even relatively easily improves the disorder if it appears.
  • the amino acid composition or the amino acid solution from which only tryptophan has been removed Is an exception, and although not as good as the amino acid composition or solution of the first invention, it has a renal dysfunction, and can be used sufficiently depending on the degree of renal dysfunction. It is desirable that this amino acid compound also contains each amino acid in the same ratio as in the first invention except for tributophan.
  • the amino acid composition of the present invention can be used for improving renal dysfunction in general, but can be used for / for especially aryleic renal dysfunction.
  • the amino acid compositions of the first and second inventions dissolve in water even when ingested as a powder, It may be taken as a solution or the like.
  • the ingestion method can also be administered via a suitable administration route such as oral administration, rectal administration, intravenous injection, and infusion.
  • composition in addition to administration of the composition itself, it may be mixed with pharmaceutically acceptable carriers, excipients, and diluents, and used as a powder, granule, m-pouch (troche, etc.)
  • suitable excipients for example salts such as sodium chloride, pH modifiers
  • it may be dissolved in sterile distilled water after adding an appropriate slow-release or isotonic agent.
  • the timing of ingestion is not particularly limited, and it can be taken at any time before and after renal dysfunction appears. It is preferable to ingest as a drink as a drug for the purpose of). Since the amino acid composition of the present invention has low toxicity, its dosage can be set widely, and it is usually 0.5 to 5 g at a time, preferably 1 to 5 at a time, depending on the administration method and purpose of use. 2 g, 1 to 20 g, preferably 4 to 10 g per day. When administered or ingested as a solution, the solution is administered or ingested as a solution of about 0.5 to 10% by weight at a time, 10 to 1000 ml at a time, preferably 1 to 4% by weight at a time, 100 to 400 ml.
  • the amino acid compositions of the first and second inventions have a remarkable inhibitory and healing effect on renal dysfunction, and the amino acid compositions are naturally occurring amino acids. Since it is derived from acid, it has low toxicity and has an extremely effective renal dysfunction improving effect.
  • the amino acid composition of the present invention may be used as a solution, particularly as an aqueous solution.
  • the solution of the first or second invention may be dissolved in water to prepare a solution.
  • the above-mentioned composition may be realized in a solution by separately dissolving the individual amino acids in water.
  • FIG. 1 is a graph showing the concentration of urea nitrogen when each amino acid composition was administered to a group of mice in which alcoholic renal dysfunction had occurred.
  • FIG. 2 is a graph showing the acute poisoning mortality when each amino acid composition was administered to a group of mice in which alcoholic renal dysfunction occurred.
  • FIG. 3 is a graph showing the knockdown rate when each amino acid composition was administered to a group of mice in which alcoholic renal dysfunction occurred.
  • urea nitrogen the most important product of nitrogen-containing substances and is excreted mainly through the kidneys. Therefore, measurement of urea is an important index for diagnosing renal dysfunction and observing the course of initial therapy.
  • Diacetyl monooxime 59 millimoles Z lit
  • the urea nitrogen key of the measurement sample was measured using a line created using a standard sample.
  • mice 6 to 8 week old ddy male mice (SPF) are given in groups of 5 and fed with unlimited feed ⁇ !? They were raised in a clean room.
  • SPF ddy male mice
  • Example 2 and Comparative Examples 1 to 10 the same ⁇ night was administered to 10 to 12 mice, respectively.
  • a sickle night containing a composition (VAAM) of 17 kinds of amino acids having a predetermined composition shown in the column of Example 1 in Table 1 was prepared by mixing commercially available amino acids and dissolving in water. .
  • This test was orally administered to a disgusting mouse every 12 hours at a dose of 37.5 1 / g body weight. The administration was carried out under these conditions from the first to the fifth administration, and the sixth administration was forcibly induced alcoholic renal dysfunction by administering the same amount of 25% ethanol instead of the nutrient solution. The administration was stopped, and 12 hours after the ethanol administration, the abdominal vena cava was removed. The blood was allowed to stand at room temperature for 30 minutes afterwards, the supernatant was centrifuged, and the urea nitrogen concentration was measured as described above.
  • V—Trp (Example 2)
  • CAAM Comparative Example 1
  • Example 2 V-9 (Comparative Example 3), V-Tyr (Comparative Example 4) and V-Lys (Comparative Example 5) were administered to a mouse under the same conditions as in Example 1 and the strength was 25%.
  • the urea nitrogen boat was measured 12 hours after throwing ethanol.
  • DW Comparative Example 6, distilled water
  • Trp Comparative Example 7, 2% tributophan aqueous solution
  • 0.25% Tyr Comparative Example 8, 0.25% tyrosine aqueous solution
  • 2% Lys Comparative Example 9, 2% lysine in water and control (Comparative Example 10, amino acids, eel, water and alcohol, etc.) And the concentration was measured).
  • mice treated with each amino acid composition is shown in Fig. 2 ⁇ Z
  • the symbols a to h attached to the amount of urea tt element in each amino acid composition in the graph of Fig. 1 indicate that there is no significant difference in the amount of urea nitrogen between two or more amino acid compositions having the same sign. ing. For example, there is no significant difference between VAAM and V— Since there is no common sign between M and DW, there is a significant difference in the amount of urea nitrogen between the two;
  • VAAM of Example 1 had significantly lower urea nitrogen than any of the remaining amino acid compositions except for the control and V-Trp. It has been clarified that the amino acid composition containing no tryptophan has a high effect of improving renal function.
  • the acute poisoning mortality shown in Figure 2 was zero for V-Tyr and slightly more than 5% for VAAM and CAAM. 2% Tru and V-Lys exceeded 15%, V-Trp reached 20%, and V-9 exceeded 20%. D. W. reached 25%, and V-1 reached around 30%. Thus, VAAM was less toxic than other amino acid compositions.
  • VAAM was the lowest, and the knockdown rate of other amino acid compositions reached 2.5 to 7 times that of VAAM. Especially in V-Tyr where mortality was 0 The highest downtime rate was reached, reaching nearly 70%.
  • the acute poisoning mortality and knockdown rate of the mice shown in Figures 2 and 3, respectively, were the lowest in VAAM (excluding the acute poisoning mortality in V-Tyr), with about 6% and about 11%, respectively. there were.
  • Acute poisoning mortality rate and knockdown rate are as low as 20% and 30%, respectively, for V-Trp as described above.
  • the effect of improving renal dysfunction is excellent, but the level of toxicity is satisfactory. However, it was also superior to many other amino acid compositions in this toxicity.
  • V—Trp which is a composition obtained by removing tributane from VAAM, is
  • VAAM Although not as effective as VAAM, it has an effect of improving renal dysfunction. However, it was found that when amino acids were further removed, the renal dysfunction was reduced and the use was not sufficiently improved.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des compositions ou des solutions d'acides aminés utilisées pour améliorer l'insuffisance rénale, caractérisées en ce qu'elles contiennent de la thréonine, de la proline, de la glycine, de la valine, de l'isoleucine, de la leucine, de la tyrosine, de la phénylalanine, de la lysine, de l'acide aspartique, de la sérine, de l'acide glutamique, de l'alanine, de la méthionine, du tryptophan, de l'histidine et de l'arginine ; ainsi que des compositions ou des solutions d'acides aminés supprimant le tryptophan de celles décrites ci-dessus. Ces compositions d'acides aminés présentent un faible taux d'azote d'urée, facteur constituant une indication de l'effet de ces compositions pour améliorer l'insuffisance rénale. En cas d'utilisation de ces compositions d'acides aminés, l'insuffisance rénale se manifeste rarement ou, si tel est le cas, elle peut être améliorée relativement rapidement.
PCT/JP2002/002501 2001-03-15 2002-03-15 Compositions d'acides amines pour ameliorer l'insuffisance renale WO2002074303A1 (fr)

Applications Claiming Priority (2)

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JP2001-74965 2001-03-15
JP2001074965A JP2002275059A (ja) 2001-03-15 2001-03-15 腎機能障害改善用アミノ酸組成物

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11173143B2 (en) * 2017-08-30 2021-11-16 Asahi Group Holdings, Ltd. Composition for decreasing serum uric acid level

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20080041675A (ko) * 2005-08-04 2008-05-13 아지노모토 가부시키가이샤 산화형 알부민 저하제
IT1397446B1 (it) * 2010-01-12 2013-01-10 Professional Dietetics Srl Compositions comprising amino acids for prevention and/or treatment of renal disorders.

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS568312A (en) * 1979-07-03 1981-01-28 Otsuka Pharmaceut Factory Inc Amino acid pharmaceutical preparation
JPH03128318A (ja) * 1989-06-14 1991-05-31 Rikagaku Kenkyusho 筋力持続剤，滋養強壮剤，輸液用剤，栄養補給剤，疲労回復剤及び乳酸生成調節剤
JPH03204814A (ja) * 1989-10-09 1991-09-06 Otsuka Pharmaceut Factory Inc 腎不全用経口アミノ酸製剤
JPH04159219A (ja) * 1990-10-23 1992-06-02 Otsuka Pharmaceut Factory Inc 腎不全用経口アミノ酸製剤
WO1994014430A1 (fr) * 1992-12-22 1994-07-07 Baxter International Inc. Solutions d'aminoacides ameliorees destinees au traitement de patients soumis a la dialyse peritoneale
JPH11302164A (ja) * 1998-04-20 1999-11-02 Shimizu Pharmaceutical Co Ltd アミノ酸組成物

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0624977A (ja) * 1992-07-10 1994-02-01 Rikagaku Kenkyusho 抗肥満剤及び抗高脂血症剤
WO2001005383A2 (fr) * 1999-07-16 2001-01-25 Mallinckrodt, Inc. Inhibition de l'absorption renale de molecules pouvant potentiellement endommager les reins

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS568312A (en) * 1979-07-03 1981-01-28 Otsuka Pharmaceut Factory Inc Amino acid pharmaceutical preparation
JPH03128318A (ja) * 1989-06-14 1991-05-31 Rikagaku Kenkyusho 筋力持続剤，滋養強壮剤，輸液用剤，栄養補給剤，疲労回復剤及び乳酸生成調節剤
JPH03204814A (ja) * 1989-10-09 1991-09-06 Otsuka Pharmaceut Factory Inc 腎不全用経口アミノ酸製剤
JPH04159219A (ja) * 1990-10-23 1992-06-02 Otsuka Pharmaceut Factory Inc 腎不全用経口アミノ酸製剤
WO1994014430A1 (fr) * 1992-12-22 1994-07-07 Baxter International Inc. Solutions d'aminoacides ameliorees destinees au traitement de patients soumis a la dialyse peritoneale
JPH11302164A (ja) * 1998-04-20 1999-11-02 Shimizu Pharmaceutical Co Ltd アミノ酸組成物

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11173143B2 (en) * 2017-08-30 2021-11-16 Asahi Group Holdings, Ltd. Composition for decreasing serum uric acid level

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