WO2003059338A1 - Process for producing liquid preparation containing branched amino acids - Google Patents
Process for producing liquid preparation containing branched amino acids Download PDFInfo
- Publication number
- WO2003059338A1 WO2003059338A1 PCT/JP2003/000218 JP0300218W WO03059338A1 WO 2003059338 A1 WO2003059338 A1 WO 2003059338A1 JP 0300218 W JP0300218 W JP 0300218W WO 03059338 A1 WO03059338 A1 WO 03059338A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- liquid preparation
- leucine
- branched
- isoleucine
- Prior art date
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 11
- 150000001413 amino acids Chemical class 0.000 title abstract description 12
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 28
- 229960000310 isoleucine Drugs 0.000 claims abstract description 28
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims abstract description 28
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 26
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 26
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 15
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000004474 valine Substances 0.000 claims abstract description 15
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000007524 organic acids Chemical class 0.000 claims abstract description 12
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 10
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 8
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011975 tartaric acid Substances 0.000 claims abstract description 6
- 235000002906 tartaric acid Nutrition 0.000 claims abstract description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims abstract description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims abstract description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims abstract description 4
- 235000015165 citric acid Nutrition 0.000 claims abstract description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims abstract description 3
- 239000001630 malic acid Substances 0.000 claims abstract description 3
- 235000011090 malic acid Nutrition 0.000 claims abstract description 3
- 235000011007 phosphoric acid Nutrition 0.000 claims abstract description 3
- 150000005693 branched-chain amino acids Chemical class 0.000 claims description 34
- 238000004519 manufacturing process Methods 0.000 claims description 19
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 claims description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 7
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- 239000000605 aspartame Substances 0.000 claims description 6
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 6
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- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 4
- 239000003765 sweetening agent Substances 0.000 claims description 4
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 3
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- 239000000594 mannitol Substances 0.000 claims description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 3
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- 239000000243 solution Substances 0.000 description 24
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- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
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- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000619 acesulfame-K Substances 0.000 description 2
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- 239000006166 lysate Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- WQNHWIYLCRZRLR-UHFFFAOYSA-N 2-(3-hydroxy-2,5-dioxooxolan-3-yl)acetic acid Chemical compound OC(=O)CC1(O)CC(=O)OC1=O WQNHWIYLCRZRLR-UHFFFAOYSA-N 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- ILRKKHJEINIICQ-OOFFSTKBSA-N Monoammonium glycyrrhizinate Chemical compound N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O ILRKKHJEINIICQ-OOFFSTKBSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000008370 chocolate flavor Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
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- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
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- 230000000857 drug effect Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
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- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229960003707 glutamic acid hydrochloride Drugs 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 239000001685 glycyrrhizic acid Substances 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- 229940074774 glycyrrhizinate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 229940057106 isoleucine / leucine / valine Drugs 0.000 description 1
- NFLGAXVYCFJBMK-UHFFFAOYSA-N isomenthone Natural products CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
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- 238000003860 storage Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- CCXAYLQLOLXXKE-DWJAGBRCSA-K trisodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4s,5s,6s)-2-[[(3s,4ar,6ar,6bs,8as,11s,12ar,14ar,14bs)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1h-picen-3-yl]oxy]-6-carboxylato-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-t Chemical compound [Na+].[Na+].[Na+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C([O-])=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O CCXAYLQLOLXXKE-DWJAGBRCSA-K 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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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
- A61K31/185—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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to a liquid preparation for a pharmaceutical or health drink containing only three kinds of branched chain amino acids of isoleucine, leucine and palline as an amino acid component as an active ingredient, and a method for producing the same.
- the present invention is a solution containing three types of branched chain amino acids consisting of isoleucine, leucine, and valine, which have strong bitterness, as active ingredients in a high concentration, and the dose per dose is reduced.
- the present invention relates to a solution capable of producing a liquid or syrup for a health drink or a medicine and a method for producing the same.
- Preparations containing three types of branched-chain amino acids consisting of isoleucine, leucine and palin as active ingredients are effective remedies for liver diseases, but currently marketed preparations mainly consist of granules.
- the single dose is about 5 g, which is significantly higher than that of general preparations, and is difficult to take due to the strong bitterness. is there.
- the liquid volume is small in terms of ease of taking and portability, and many liquids have a single dose of 10 OmL or less.
- the solubility in water in the neutral region is low.
- the solubility of leucine is 2.3 g at 10 ° C, 2.4 g of ZdL and 20 ° C. / dL, which is extremely low, when preparing a liquid preparation of 10 OmL or less containing 4 g of branched-chain amino acids, there were problems such as crystallization during the distribution process or during refrigerated storage.
- the present invention relates to the use of three types of branched-chain amino acids consisting of isoleucine, leucine, and valine, which are effective therapeutic agents for liver diseases, as an active ingredient in a liquid medicine or health drink for each dose.
- the aim is to reduce the volume and improve the ingestibility.
- the inventors of the present invention have conducted intensive studies and found that, in the step of dissolving the raw material in the production process of the branched chain amino acid-containing liquid preparation, the addition of an organic acid and / or an inorganic acid results in a branched chain
- a high-concentration solution can be prepared by improving the solubility of amino acids, and the prepared solution masks the bitterness peculiar to branched-chain amino acids by the added acid, making it easy to take.
- the present invention includes the following inventions.
- the total amount of the three types of branched-chain amino acids of isoleucine, leucine and palline dissolved per 10 OmL of the liquid preparation is not less than 4. Og, any one of (1) to (3).
- the liquid preparation for pharmaceuticals or health drinks of the present invention is a liquid preparation prepared as an aqueous solution in which three kinds of branched-chain amino acids consisting of isoleucine, oral isine and valine as active ingredients are dissolved at a high concentration.
- Examples of the inorganic acid used for producing the liquid preparation for medical or health drinks of the present invention include carbonic acid, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and boric acid. Acids are preferred.
- the organic acids include cunic acid, cunic anhydride, d-monomalic acid, tartaric acid, d-tartaric acid, ascorbic acid, acetic acid, lactic acid, succinic acid, Maleic acid, malonic acid, 1-glutamic acid hydrochloride and the like can be mentioned, and particularly, citric acid, citric anhydride, dl-malic acid, tartaric acid, d-tartaric acid, ascorbic acid, acetic acid and the like are preferable.
- a sweetener / flavoring agent may be added to the pharmaceutical or health drink solution of the present invention.
- sweeteners / flavors include aspartame, saccharin, sodium saccharin, glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium darityl ritinate, dipotassium glycyrrhizinate, ninatrium glycyrrhizinate, trisodium glycyrrhizinate, acesulfame K, acesulfame K Erythritol, sorbitol, xylitol and trehalose.
- Particularly preferred are aspartame, saccharin, saccharin sodium, mannitol and the like.
- Flavoring agents can be used in the liquid preparation for medicine or health drink of the present invention.
- Various flavors can be used as such a flavoring agent, and examples thereof include lemon flavor, orange flavor, grapefruit flavor, chocolate flavor, dl-menthol, and 1-menthol.
- the isoleucine raw material, leucine raw material and palin raw material as active ingredients are generally produced by a fermentation method and crushed into particles having a particle size of 1 mm or less. There are no particular restrictions on the particle size and the like as long as they can be dissolved in water according to the method of the present invention.
- the liquid preparation containing only the above three kinds of branched-chain amino acids as the amino acid component in the liquid preparation for medical use or health food of the present invention can also be produced by using equipment such as a dissolving tank having a stirring blade, a high-speed homogenizer and the like. . In addition, by heating during dissolution, the preparation time can be reduced.
- Example 1 After pouring 900 g of heated distilled water into a glass beaker (capacity: 2 liters), add 19.04 g of isine, 9.52 g of isoleucine, 1.44 g of phosphorus, and 1.44 g of citric acid monohydrate. 7 g, aspartame 30 g and d-mannitol 7.50 g were weighed, added and dissolved with stirring (equivalent to 10 doses). The solution was cooled to room temperature, and the pH was measured to be 3.4. From this solution, a liquid preparation in which 4.0 g of the branched-chain amino acid was dissolved in about 94 mL of the liquid per dose could be prepared. No precipitate was observed when the obtained solution was cooled in a refrigerator (about 418) for 24 hours.
- Example 2 After pouring 900 g of heated distilled water into a glass beaker (capacity: 2 liters), add 19.04 g of isine, 9.52 g of isoleucine, 1.44
- the liquid formulation consisting of a branched-chain amino acid solution whose pH has been acidified by an acid such as an organic acid is one in which the bitterness inherent in branched-chain amino acids is effectively reduced.
- the method of the present invention can produce a solution in which only three kinds of branched-chain amino acids consisting of isoleucine, leucine, and valine are dissolved at a high concentration as amino acid components as active ingredients. It is possible to prepare the branched-chain amino acid-containing liquid preparation in which the amount is reduced to 10 OmL or less, and the bitterness of the raw material branched-chain amino acid due to the acid added at the time of preparing the solution. With the addition of the drug effect, it has become possible to provide a liquid preparation with further improved takeability.
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Abstract
It is intended to provide a liquid preparation containing, as the active ingredients, three branched amino acids, i.e., isoleucine, leucine and valine, at high concentrations and a process for producing the same. Namely, a liquid preparation for medicinal or health drinks containing, as the active ingredients, three branched amino acids, i.e., isoleucine, leucine and valine, at high concentrations and a process for producing the same characterized in that the three branched amino acids, i.e., isoleucine, leucine and valine are dissolved in water in the presence of an organic acid and/or an inorganic acid such as citric acid, tartaric acid, malic acid, succinic acid, phosphoric acid, carbonic acid or hydrochloric acid.
Description
明 細 書 Specification
分岐鎖アミノ酸含有液剤の製造方法 技術分野 Method for producing branched chain amino acid-containing solution
本発明は、 有効成分であるアミノ酸成分としてイソロイシン、 ロイシン及びパ リンの 3種の分岐鎖アミノ酸のみを含有する医薬用又は健康飲料用の液剤とその 製造方法に関する。 The present invention relates to a liquid preparation for a pharmaceutical or health drink containing only three kinds of branched chain amino acids of isoleucine, leucine and palline as an amino acid component as an active ingredient, and a method for producing the same.
特に、 本発明は、 有効成分として苦みの強いイソロイシン、 ロイシン、 及びバ リンからなる 3種の分岐鎖アミノ酸を高濃度で溶解含有している溶液であり、 1 回当たりの服用量を少量化した健康飲料用又は医薬用の液剤やシロップ剤の製造 を可能とした溶液とその製造方法に関するものである。 背景技術 In particular, the present invention is a solution containing three types of branched chain amino acids consisting of isoleucine, leucine, and valine, which have strong bitterness, as active ingredients in a high concentration, and the dose per dose is reduced. The present invention relates to a solution capable of producing a liquid or syrup for a health drink or a medicine and a method for producing the same. Background art
イソロイシン、 ロイシン及びパリンからなる 3種の分岐鎖アミノ酸を有効成分 として含む製剤は肝疾患に有効な治療薬であるが、 現在市販されている製剤は顆 粒剤が主体である。 Preparations containing three types of branched-chain amino acids consisting of isoleucine, leucine and palin as active ingredients are effective remedies for liver diseases, but currently marketed preparations mainly consist of granules.
上記 3種の分岐鎖アミノ酸を含有する顆粒製剤の場合、 その 1回の服用量が約 5 gと一般の製剤に比較して著しく多く、 しかも苦みが強いことから服用しにく いという難点がある。 In the case of granules containing the above three types of branched-chain amino acids, the single dose is about 5 g, which is significantly higher than that of general preparations, and is difficult to take due to the strong bitterness. is there.
一方、 1回の服用量が多くて服用しにくい薬剤を、 服用時に水を必要とせず咽 喉越しもよい液剤とすることも行われている。 分岐鎖アミノ酸を有効成分とする アミノ酸液剤としては、 疲労の予防又は回復のための経口投与剤として報告があ るが（特開平 7 _ 2 5 8 3 8号公報）、その液量は分岐鎖アミノ酸であるロイシン 2 g当り約 2 0 0 m Lと非常に多量なものであった。 On the other hand, drugs that are difficult to take due to a large dose per dose are also being converted to liquids that do not require water when taken and can pass through the throat. An amino acid solution containing a branched-chain amino acid as an active ingredient has been reported as an orally administered drug for preventing or recovering from fatigue (Japanese Patent Application Laid-Open No. 7-25838). It was a very large amount of about 200 mL per 2 g of the amino acid leucine.
また、 服用しにくい薬剤を液剤とするために、 その溶解量を多くすることも知 られており、 ビタミン類等ではナトリゥム塩とすることにより溶解度向上の試み がなされているものもある （特公平 2— 1 2 5 4 9公報）。 しかし、 本発明で液剤 化しようとしているイソロイシン、 ロイシン及びバリンからなる 3種の分岐鎖ァ ミノ酸の場合は、 ナトリゥム塩とすると苦味が強くなる傾向がありさらに服用し
にくくなるのみならず、 溶液がアルカリ性となるので医薬品、 食品の用途に適さ なくなるので採用することはできない。 発明の開示 It is also known to increase the solubility of drugs that are difficult to take in liquid form. For vitamins, etc., attempts have been made to improve the solubility by using sodium salts (see Tokuhei Koho) 2-1 2 5 4 9 publication). However, in the case of the three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine to be made into a liquid preparation in the present invention, if sodium salt is used, the bitter taste tends to become stronger, and further administration is required. Not only will it be difficult to use, but the solution will be alkaline, making it unsuitable for pharmaceutical and food applications, and cannot be adopted. Disclosure of the invention
—般的に、 医療用液剤においては、 服用し易さと携帯性の点から液量は少ない ことが望ましく、 1回服用量 1 0 O m L以下である液剤が多い。 —Generally, for medical liquids, it is desirable that the liquid volume is small in terms of ease of taking and portability, and many liquids have a single dose of 10 OmL or less.
しかし、 当該分岐鎖アミノ酸を含有する液剤においては、 中性域における水に 対する溶解度が低く、 特にロイシンの溶解度は 1 0 °Cで 2 . 3 g Z d L、 2 0 °C 2 . 4 g / d Lと極めて低いため、 分岐鎖アミノ酸量 4 gを含有する 1 0 O m L 以下の液剤を調製した場合、 流通過程又は冷蔵保存時において結晶化してしまう 等の問題があった。 However, in the solution containing the branched-chain amino acid, the solubility in water in the neutral region is low. In particular, the solubility of leucine is 2.3 g at 10 ° C, 2.4 g of ZdL and 20 ° C. / dL, which is extremely low, when preparing a liquid preparation of 10 OmL or less containing 4 g of branched-chain amino acids, there were problems such as crystallization during the distribution process or during refrigerated storage.
本発明の課題は、 1回服用当たりの服用量が少なく、 服用性の良好なイソロイ シン、 ロイシン及びバリンの 3種の分岐鎖アミノ酸を有効成分とする医薬用又は 健康飲料用の液剤とその製造方法を提供することにある。 It is an object of the present invention to provide a pharmaceutical or health drink liquid preparation comprising three types of branched chain amino acids of isoleucine, leucine and valine, which have a low dose per dose and have good ingestibility, and their production. It is to provide a method.
特に、 本発明は、 肝疾患に対する有効な治療薬であるイソロイシン、 ロイシン 及びバリンからなる 3種の分岐鎖アミノ酸を有効成分とする医薬用及び健康飲料 用の液剤の 1回服用当たりの液量を小容量化して服用性を改善することを目的と するものである。 In particular, the present invention relates to the use of three types of branched-chain amino acids consisting of isoleucine, leucine, and valine, which are effective therapeutic agents for liver diseases, as an active ingredient in a liquid medicine or health drink for each dose. The aim is to reduce the volume and improve the ingestibility.
上記課題を解決するため、 本発明者らは鋭意検討を重ねた結果、 分岐鎖ァミノ 酸含有液剤の製造工程における原料の溶解工程において、 有機酸及び/又は無機 酸を添加することにより、 分岐鎖アミノ酸の溶解性を向上させて高濃度の溶液を 調製することができること、 及びそのようにして調製した溶液は、 添加されてい る酸によって分岐鎖アミノ酸特有の苦味がマスキングされていて服用し易くなつ ていることを見出し、 本発明を完成するに至った。 本発明は、 以下の各発明を包 含する。 In order to solve the above problems, the inventors of the present invention have conducted intensive studies and found that, in the step of dissolving the raw material in the production process of the branched chain amino acid-containing liquid preparation, the addition of an organic acid and / or an inorganic acid results in a branched chain A high-concentration solution can be prepared by improving the solubility of amino acids, and the prepared solution masks the bitterness peculiar to branched-chain amino acids by the added acid, making it easy to take. And completed the present invention. The present invention includes the following inventions.
( 1 ) イソロイシン、 ロイシン及びパリンからなる 3種の分岐鎖アミノ酸を有機 酸及ぴ Z又は無機酸の存在下に水に溶解させることを特徴とする、イソロイシン、 ロイシン及びバリンからなる 3種の分岐鎖アミノ酸を有効成分として髙濃度で含 有する液剤の製造方法。
(2)有機酸、無機酸を添加した分岐鎖アミノ酸溶液の pHが 6. 0以下である、 (1) 記載の液剤の製造方法。 (1) Three types of branches consisting of isoleucine, leucine and valine, characterized in that three types of branched-chain amino acids consisting of isoleucine, leucine and palin are dissolved in water in the presence of an organic acid and Z or an inorganic acid. A method for producing a liquid preparation comprising a low-concentration amino acid as an active ingredient in a low concentration. (2) The method for producing a liquid preparation according to (1), wherein the pH of the branched-chain amino acid solution to which an organic acid or an inorganic acid is added is 6.0 or less.
(3)有機酸、無機酸を添加した分岐鎖アミノ酸溶液の pHが 4. 5以下である、 (1)記載の液剤の製造方法。 (3) The method for producing a liquid preparation according to (1), wherein the pH of the branched-chain amino acid solution to which an organic acid or an inorganic acid is added is 4.5 or less.
(4) 前記液剤 10 OmL当たりに溶解しているイソロイシン、 ロイシン及びパ リンの 3種の分岐鎖アミノ酸の合計量が 4. O g以上である、 （1) 〜 （3) のい ずれか 1項に記載の液剤の製造方法。 (4) The total amount of the three types of branched-chain amino acids of isoleucine, leucine and palline dissolved per 10 OmL of the liquid preparation is not less than 4. Og, any one of (1) to (3). The method for producing a liquid preparation according to the above item.
(5)前記有機酸及び/又は無機酸が、 クェン酸、 酒石酸、 リンゴ酸、 コハク酸、 リン酸、 炭酸及び塩酸から選ばれる少なくとも 1種である、 （1) 〜 （4) のいず れか 1項に記載の液剤の製造方法。 (5) any one of (1) to (4), wherein the organic acid and / or inorganic acid is at least one selected from citric acid, tartaric acid, malic acid, succinic acid, phosphoric acid, carbonic acid and hydrochloric acid. Or the method for producing a liquid preparation according to item 1.
(6) イソロイシン、 ロイシン及びパリンの質量比が、 イソロイシン/口イシン /バリン = 1 Z 1. 9〜2. 2/ 1. 1〜 1. 3である、 （1) 〜 （5) のいずれ か 1項に記載の液剤の製造方法。 (6) Any of (1) to (5), wherein the mass ratio of isoleucine, leucine, and palin is isoleucine / mouth isin / valine = 1Z1.9 to 2.2 / 1.1 to 1.3. 2. The method for producing a liquid preparation according to item 1.
(7) 甘味剤としてアスパルテーム、 サッカリン、 サッカリンナトリゥム及びマ ンニトールのうちの 1種類以上を添加することを特徴とする （1) 〜 （6) のい ずれか 1項に記載の液剤の製造方法。 (7) The method for producing a liquid preparation according to any one of (1) to (6), wherein at least one of aspartame, saccharin, saccharin sodium and mannitol is added as a sweetener. .
(8) 前記 （1) 〜 （7) のいずれか 1項に記載の製造方法により製造されてい る、 イソロイシン、 ロイシン及びパリンの 3種の分岐鎖アミノ酸を有効成分とし て高濃度で含有する液剤。 (8) A liquid preparation containing three kinds of branched-chain amino acids of isoleucine, leucine and palin as active ingredients at a high concentration, which is produced by the production method according to any one of the above (1) to (7). .
本発明の医薬用又は健康飲料用の液剤は、 有効成分としてのイソロイシン、 口 イシン及びバリンからなる 3種の分岐鎖アミノ酸を高濃度で溶解している水溶液 として製造されている液剤である。 The liquid preparation for pharmaceuticals or health drinks of the present invention is a liquid preparation prepared as an aqueous solution in which three kinds of branched-chain amino acids consisting of isoleucine, oral isine and valine as active ingredients are dissolved at a high concentration.
本発明の医薬用又は健康飲料用の液剤におけるイソロイシン、 口イシン及びバ リンの配合割合は、 質量比で、 イソロイシン/ロイシン/バリン = 1 / 1. 9〜 2. 2/ 1. 1〜1. 3であることが好ましい。 The mixing ratio of isoleucine, mouth isine and valine in the liquid preparation for pharmaceuticals or health drinks of the present invention is isoleucine / leucine / valine = 1 / 1.9 to 2.2 / 1.1-1 to 1. It is preferably 3.
本発明の医薬用又は健康飲料用の液剤の製造のために使用される無機酸として は、 炭酸、 塩酸、 硫酸、 硝酸、 リン酸、 ホウ酸等があげられるが、 特に、 炭酸、 塩酸、 リン酸が好ましい。 また、 有機酸としては、 クェン酸、 無水クェン酸、 d 1一リンゴ酸、 酒石酸、 d—酒石酸、 ァスコルビン酸、 酢酸、 乳酸、 コハク酸、
マレイン酸、 マロン酸、 1 一グルタミン酸塩酸塩等があげられるが、 特に、 クェ ン酸、 無水クェン酸、 d l —リンゴ酸、 酒石酸、 d—酒石酸、 ァスコルビン酸、 酢酸等が好ましい。 Examples of the inorganic acid used for producing the liquid preparation for medical or health drinks of the present invention include carbonic acid, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and boric acid. Acids are preferred. The organic acids include cunic acid, cunic anhydride, d-monomalic acid, tartaric acid, d-tartaric acid, ascorbic acid, acetic acid, lactic acid, succinic acid, Maleic acid, malonic acid, 1-glutamic acid hydrochloride and the like can be mentioned, and particularly, citric acid, citric anhydride, dl-malic acid, tartaric acid, d-tartaric acid, ascorbic acid, acetic acid and the like are preferable.
本発明の医薬用又は健康飲料用の液剤には甘味剤 ·矯味剤を添加してもよい。 そのような甘味剤 ·矯味剤としては、 アスパルテーム、 サッカリン、 サッカリン ナトリウム、 グリチルリチン酸、 グリチルリチン酸モノアンモニゥム、 ダリチル リチン酸二アンモニゥム、 グリチルリチン酸二カリウム、 グリチルリチン酸ニナ トリウム、 グリチルリチン酸三ナトリウム、 アセスルファム K、 マンニトール、 エリスリ トール、 ソルビトール、 キシリ トール、 トレハロースである。 特に好ま しくはアスパルテーム、 サッカリン、 サッカリンナトリウム、 マンニトール等が あげられる。 A sweetener / flavoring agent may be added to the pharmaceutical or health drink solution of the present invention. Examples of such sweeteners / flavors include aspartame, saccharin, sodium saccharin, glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium darityl ritinate, dipotassium glycyrrhizinate, ninatrium glycyrrhizinate, trisodium glycyrrhizinate, acesulfame K, acesulfame K Erythritol, sorbitol, xylitol and trehalose. Particularly preferred are aspartame, saccharin, saccharin sodium, mannitol and the like.
本発明の医薬用又は健康飲料用の液剤には着香剤を使用することができる。 そ のような着香剤としては、 各種フレーバーを用いることができるが、 例としては レモンフレーバー、 オレンジフレーバー、 グレープフルーツフレーバー、 チョコ レー卜フレーバー、 d l —メントール、 1 ーメン卜一ル等が挙げられる。 Flavoring agents can be used in the liquid preparation for medicine or health drink of the present invention. Various flavors can be used as such a flavoring agent, and examples thereof include lemon flavor, orange flavor, grapefruit flavor, chocolate flavor, dl-menthol, and 1-menthol.
本発明の医薬用又は健康飲料用の液剤において、 有効成分であるイソロイシン 原料、 ロイシン原料及びパリン原料としては、 一般的に発酵法で製造されている ものを粉砕して粒度 l mm以下とした粒子がそれぞれ使用されるが、 本発明の方 法にしたがって水に溶解できる状態のものであれば、 その粒度等に特に制限はな い。 In the pharmaceutical or health drink liquid preparation of the present invention, the isoleucine raw material, leucine raw material and palin raw material as active ingredients are generally produced by a fermentation method and crushed into particles having a particle size of 1 mm or less. There are no particular restrictions on the particle size and the like as long as they can be dissolved in water according to the method of the present invention.
本発明の医薬用又は健康食品用の液剤におけるアミノ酸成分として前記 3種の 分岐鎖アミノ酸のみを含む液剤は、 攪拌翼を有する溶解槽、 高速ホモジナイザー などの機器を使用しても製造することができる。 また溶解時に加温することによ りその調製時間の短縮化が可能となる。 発明を実施するための最良の形態 The liquid preparation containing only the above three kinds of branched-chain amino acids as the amino acid component in the liquid preparation for medical use or health food of the present invention can also be produced by using equipment such as a dissolving tank having a stirring blade, a high-speed homogenizer and the like. . In addition, by heating during dissolution, the preparation time can be reduced. BEST MODE FOR CARRYING OUT THE INVENTION
本発明の具体例を以下の実施例にしたがって説明するが、 本発明はこれらによ つて限定されるものではない。 EXAMPLES Specific examples of the present invention will be described according to the following examples, but the present invention is not limited by these.
実施例 1
ガラスビーカ一 （容量 2リツター） に加温した蒸留水 900 gを入れた後、 口 イシン 19. 04 g、 イソロイシン 9. 52 g、 ノ リン 1 1. 44 g、 クェン酸 1水和物 6. 7 g、 アスパルテーム 30 g、 d—マンニトール 7. 50 gを 秤量し、 添加して攪拌しながら溶解させた （10回服用分相当）。 溶解液を室温ま で冷却し、 pHを測定したところ pH3. 4であった。 この溶液から、 1服用液 量約 94mL中、 分岐鎖アミノ酸 4. 0 gを溶解している液剤を調製することが できた。 得られた溶液を冷蔵庫中 （約 4一 8で） で 1昼夜冷却しても析出物は観 察されなかった。 実施例 2 Example 1 After pouring 900 g of heated distilled water into a glass beaker (capacity: 2 liters), add 19.04 g of isine, 9.52 g of isoleucine, 1.44 g of phosphorus, and 1.44 g of citric acid monohydrate. 7 g, aspartame 30 g and d-mannitol 7.50 g were weighed, added and dissolved with stirring (equivalent to 10 doses). The solution was cooled to room temperature, and the pH was measured to be 3.4. From this solution, a liquid preparation in which 4.0 g of the branched-chain amino acid was dissolved in about 94 mL of the liquid per dose could be prepared. No precipitate was observed when the obtained solution was cooled in a refrigerator (about 418) for 24 hours. Example 2
ガラスビーカー （容量 1 L) に加温した蒸留水 285 gを入れた後、 ロイシン 9. 52 g、 イソロイシン 4. 76 g、 ノ リン 5. 72 g、 クェン酸 1水和物 1. 8 g、 アスパルテーム 0. 1 5 g、 d—マンニトール 3. 5 gを秤量し、 添加し て、 加温下で攪拌しながら塩酸を滴下し、 溶解させた （5回服用分相当）。 溶解液 の pHを測定しところ pH2. 2であった。 この溶液から、 1服用液量約 6 1m L中、 分岐鎖アミノ酸 4. 0 gを溶解している液剤を調製することができた。 得 られた溶液を冷蔵庫中 （約 4— 8°C) で 1昼夜冷却しても析出物は観察されなか つた。 実施例 3 After putting 285 g of heated distilled water in a glass beaker (capacity: 1 L), 9.52 g of leucine, 4.76 g of isoleucine, 5.72 g of phosphorus, 1.8 g of citric acid monohydrate, 0.15 g of aspartame and 3.5 g of d-mannitol were weighed and added, and hydrochloric acid was added dropwise while stirring with heating to dissolve (equivalent to 5 doses). The pH of the lysate was measured and was found to be 2.2. From this solution, a liquid preparation in which 4.0 g of branched-chain amino acid was dissolved in about 61 mL of the liquid dose per dose could be prepared. No precipitate was observed when the obtained solution was cooled in a refrigerator (about 4-8 ° C) for 24 hours. Example 3
ガラスビーカ一 （容量 200mL) に加温した蒸留水 85 gを入れた後、 ロイ シン 1. 904 g、 イソロイシン 0. 952 g、 ノ リン 1. 144 g、 クェン酸 1水和物 1. 2 g、 D—マンニトール 0. 1 5 、 酒石酸0. 1 5 gを秤量し、 添加した。 蒸留水 15 gを追加して攪拌しながら溶解させた （1回服用分相当）。 溶解後に pHを測定したところ pH3. 2であった。 この溶液から、 1服用液量 約 88mL中、 分岐鎖アミノ酸 4. 0 gを溶解している液剤を調製することがで きた。 得られた溶液を冷蔵庫中 （約 4— 8で） で 1昼夜冷却しても析出物は観察 されなかった。
比較例 1 After adding 85 g of heated distilled water to a glass beaker (capacity: 200 mL), 1.904 g of leucine, 0.952 g of isoleucine, 1.144 g of phosphorus, 1.2 g of citrate monohydrate 0.1 g of D-mannitol and 0.15 g of tartaric acid were weighed and added. 15 g of distilled water was added and dissolved with stirring (corresponding to one dose). After dissolution, the pH was measured, and it was pH 3.2. From this solution, it was possible to prepare a liquid preparation in which 4.0 g of branched-chain amino acid was dissolved in about 88 mL of liquid per dose. No precipitate was observed when the resulting solution was cooled in a refrigerator (about 4-8) for 24 hours. Comparative Example 1
ガラスビーカー （容量 200mL) に加温した蒸留水 93 gを入れた後、 ロイ シン 1. 904 g、 イソロイシン 0. 952 、 ノ リン1. 144 gを秤量し、 添加して、 50でで加温下攪拌しながら溶解させた。 溶解後に pHを測定したと ころ PH6. 0であった。 この溶液から、 1服用液量約 95 mLの液剤を調製し、 得られた液剤を冷蔵庫中 4一 8 °Cで 1昼夜放置したところ、 アミノ酸の結晶析出 が観察された。 実験例 After placing 93 g of heated distilled water in a glass beaker (capacity: 200 mL), weigh 1.904 g of leucine, 0.952 of isoleucine and 1.144 g of phosphorus, add, and heat at 50 The mixture was dissolved under stirring. When the pH was measured after dissolution, the pH was 6.0. From this solution, a solution of about 95 mL per dose was prepared, and the obtained solution was allowed to stand in a refrigerator at 418 ° C for 24 hours. As a result, amino acid crystal precipitation was observed. Experimental example
上記実施例 1， 2, 3及び比較例 1で調製された溶解液について、 各 5mLを ブラインド性を確保した状態で、 成人男子 5人のパネラーを用い、 各 5mLを服 用させ、 服用し易さについての官能評価を行った。 服用直後の苦味と後味 （服用 1分後の苦味） についての評価結果を表 1に示す。 - 【表 1】 5 mL of each of the lysates prepared in Examples 1, 2, 3 and Comparative Example 1 was taken using 5 adult male panelists while ensuring blindness of 5 mL. An organoleptic evaluation was performed. Table 1 shows the evaluation results for bitterness and aftertaste immediately after taking (bitterness 1 minute after taking). - 【table 1】
◎：全く気にならない苦味である ◎: bitterness that is not bothersome at all
〇： あまり気にならない苦味である 〇: Bitterness not so noticeable
△：やや気になるにがみである △: Slightly anxious bite
X ：気になる苦味である X: Bitterness to be worried about
表 1から明らかなように、 有機酸等の酸により p Hを酸性にした分岐鎖アミノ 酸溶液からなる液剤は、 分岐鎖アミノ酸固有の苦味が効果的に低減されているも のである。
産業上の利用可能性 As is evident from Table 1, the liquid formulation consisting of a branched-chain amino acid solution whose pH has been acidified by an acid such as an organic acid is one in which the bitterness inherent in branched-chain amino acids is effectively reduced. Industrial applicability
本発明の方法は、 有効成分であるアミノ酸成分としてイソロイシン、 ロイシン 及びバリンからなる 3種の分岐鎖アミノ酸のみを高濃度で溶解している溶液を製 造することができることから、 1服用当たりの服用量を 1 0 O m L以下に少量化 した前記分岐鎖アミノ酸含有液剤を調製することを可能とするものであり、 しか も、 溶液調製時に添加されている酸による原料分岐鎖アミノ酸の苦味のマスキン グ効果が追加されていることによって、 さらに服用性が改善されている液剤を提 供することを可能としたものである。
The method of the present invention can produce a solution in which only three kinds of branched-chain amino acids consisting of isoleucine, leucine, and valine are dissolved at a high concentration as amino acid components as active ingredients. It is possible to prepare the branched-chain amino acid-containing liquid preparation in which the amount is reduced to 10 OmL or less, and the bitterness of the raw material branched-chain amino acid due to the acid added at the time of preparing the solution. With the addition of the drug effect, it has become possible to provide a liquid preparation with further improved takeability.
Claims
1. イソロイシン、 ロイシン及びパリンからなる 3種の分岐鎖アミノ酸を有機酸 及び Z又は無機酸の存在下に水に溶解させることを特徴とする、 ィソロイシン、 ロイシン及びバリンからなる 3種の分岐鎖アミノ酸を有効成分として高濃度で含 有する液剤の製造方法。 1. Three kinds of branched-chain amino acids consisting of isoloicin, leucine and valine, characterized in that three kinds of branched-chain amino acids consisting of isoleucine, leucine and palin are dissolved in water in the presence of an organic acid and Z or an inorganic acid. For producing a liquid preparation containing at a high concentration as an active ingredient.
2. 有機酸、 無機酸を添加した分岐鎖アミノ酸溶液の pHが 6. 0以下である、 請求の範囲 1記載の液剤の製造方法。 2. The method for producing a liquid preparation according to claim 1, wherein the pH of the branched-chain amino acid solution to which an organic acid or an inorganic acid is added is 6.0 or less.
3. 有機酸、 無機酸を添加した分岐鎖アミノ酸溶液の pHが 4. 5以下である、 請求の範囲 1記載の液剤の製造方法。 3. The method for producing a liquid preparation according to claim 1, wherein the pH of the branched-chain amino acid solution to which an organic acid or an inorganic acid is added is 4.5 or less.
4. 前記液剤 10 OmL当たりに溶解しているイソロイシン、 ロイシン及びバリ ンの 3種の分岐鎖アミノ酸の合計量が 4. O g以上である、 請求の範囲 1〜3の いずれか 1項に記載の液剤の製造方法。 4. The method according to any one of claims 1 to 3, wherein the total amount of the three types of branched-chain amino acids of isoleucine, leucine, and valine dissolved per 10 OmL of the solution is 4.Og or more. Method for producing liquid preparations.
5. 前記有機酸及び/又は無機酸が、 クェン酸、 酒石酸、 リンゴ酸、 コハク酸、 リン酸、 炭酸及ぴ塩酸から選ばれる少なくとも 1種である、 請求の範囲 1〜4の いずれか 1項に記載の液剤の製造方法。 5. The method according to claim 1, wherein the organic acid and / or the inorganic acid is at least one selected from citric acid, tartaric acid, malic acid, succinic acid, phosphoric acid, carbonic acid, and hydrochloric acid. The method for producing a liquid preparation according to the above.
6. イソロイシン、 ロイシン及びパリンの質量比が、 イソロイシン Zロイシン/ パリン = 1ノ 1. 9〜2. 2 / 1. 1 ~ 1. 3である、 請求の範囲 1〜 5のいず れか 1項に記載の液剤の製造方法。 6. The mass ratio of isoleucine, leucine and palin is isoleucine Z-leucine / palin = 1 to 1.9 to 2.2 / 1.1 to 1.3, any one of claims 1 to 5 1 The method for producing a liquid preparation according to the above item.
7. 甘味剤としてアスパルテーム、 サッカリン、 サッカリンナトリゥム及びマン 二トールのうちの 1種類以上を添加することを特徴とする請求の範囲 1〜 6記載 の液剤の製造方法。 7. The method according to any one of claims 1 to 6, wherein one or more of aspartame, saccharin, saccharin sodium, and mannitol are added as a sweetener.
8. 請求の範囲 1〜 7のいずれか 1項に記載の製造方法により製造されている、 有効成分としてイソロイシン、 ロイシン及びバリンの 3種の分岐鎖アミノ酸を高 濃度で含有する液剤。
8. A liquid preparation containing three types of branched-chain amino acids of isoleucine, leucine and valine as active ingredients at a high concentration, which is produced by the production method according to any one of claims 1 to 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003203159A AU2003203159A1 (en) | 2002-01-15 | 2003-01-14 | Process for producing liquid preparation containing branched amino acids |
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|---|---|---|---|
| JP2002006129A JP3368897B1 (en) | 2002-01-15 | 2002-01-15 | Process for producing branched chain amino acid-containing liquid agent |
| JP2002-006129 | 2002-01-15 |
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| WO2003059338A1 true WO2003059338A1 (en) | 2003-07-24 |
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| PCT/JP2003/000218 WO2003059338A1 (en) | 2002-01-15 | 2003-01-14 | Process for producing liquid preparation containing branched amino acids |
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| JP (1) | JP3368897B1 (en) |
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| JPWO2007023999A1 (en) * | 2005-08-24 | 2009-03-05 | 味の素株式会社 | Amino acid-containing acidic beverage and method for producing the same |
| JP5448248B2 (en) * | 2007-03-26 | 2014-03-19 | 味の素株式会社 | Food containing isoleucine in containers |
| JP5295073B2 (en) * | 2009-10-30 | 2013-09-18 | 株式会社ゼロベース | Health supplements |
| EP2984944A4 (en) * | 2013-03-07 | 2016-08-31 | Ajinomoto Kk | Aqueous liquid composition including high concentration of l-histidine |
| JP2013208128A (en) * | 2013-06-10 | 2013-10-10 | Zero Base:Kk | Dietary supplement |
| JP6802627B2 (en) * | 2014-12-19 | 2020-12-16 | ハウス食品株式会社 | Leucine bitterness reducing agent and leucine bitterness reducing method |
| WO2019009251A1 (en) * | 2017-07-03 | 2019-01-10 | 味の素株式会社 | Beverage |
| JP7000877B2 (en) * | 2018-01-25 | 2022-01-19 | 味の素株式会社 | Manufacturing method of foods containing amino acids |
| JPWO2020262455A1 (en) | 2019-06-25 | 2020-12-30 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05148149A (en) * | 1991-07-26 | 1993-06-15 | Green Cross Corp:The | Transfusion pharmaceutical |
| JPH0624971A (en) * | 1992-03-20 | 1994-02-01 | Clintec Nutrition Co | Highly concentrated amino acid solution |
| JPH0725838A (en) * | 1993-05-13 | 1995-01-27 | Yotsuba Yuka Kk | Orally administering agent for preventing or recovering fatigue |
-
2002
- 2002-01-15 JP JP2002006129A patent/JP3368897B1/en not_active Expired - Fee Related
-
2003
- 2003-01-14 AU AU2003203159A patent/AU2003203159A1/en not_active Abandoned
- 2003-01-14 WO PCT/JP2003/000218 patent/WO2003059338A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05148149A (en) * | 1991-07-26 | 1993-06-15 | Green Cross Corp:The | Transfusion pharmaceutical |
| JPH0624971A (en) * | 1992-03-20 | 1994-02-01 | Clintec Nutrition Co | Highly concentrated amino acid solution |
| JPH0725838A (en) * | 1993-05-13 | 1995-01-27 | Yotsuba Yuka Kk | Orally administering agent for preventing or recovering fatigue |
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| AU2003203159A1 (en) | 2003-07-30 |
| JP3368897B1 (en) | 2003-01-20 |
| JP2003212766A (en) | 2003-07-30 |
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