JP5764281B2 - 血液流動性改善剤 - Google Patents
血液流動性改善剤 Download PDFInfo
- Publication number
- JP5764281B2 JP5764281B2 JP2008520586A JP2008520586A JP5764281B2 JP 5764281 B2 JP5764281 B2 JP 5764281B2 JP 2008520586 A JP2008520586 A JP 2008520586A JP 2008520586 A JP2008520586 A JP 2008520586A JP 5764281 B2 JP5764281 B2 JP 5764281B2
- Authority
- JP
- Japan
- Prior art keywords
- blood
- mol
- amino acid
- fluidity
- blood flow
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 210000004369 blood Anatomy 0.000 title claims description 93
- 239000008280 blood Substances 0.000 title claims description 93
- 229940024606 amino acid Drugs 0.000 claims description 48
- 235000001014 amino acid Nutrition 0.000 claims description 48
- 150000001413 amino acids Chemical class 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 41
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 24
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 16
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 16
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 15
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 14
- 229960000310 isoleucine Drugs 0.000 claims description 14
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 13
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 13
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 13
- 239000003638 chemical reducing agent Substances 0.000 claims description 13
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 12
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 12
- 239000004472 Lysine Substances 0.000 claims description 12
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 12
- 229930182817 methionine Natural products 0.000 claims description 12
- 239000004474 valine Substances 0.000 claims description 12
- 239000004475 Arginine Substances 0.000 claims description 11
- 239000004471 Glycine Substances 0.000 claims description 11
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 11
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 11
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 11
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 11
- 235000009697 arginine Nutrition 0.000 claims description 11
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 11
- 235000014304 histidine Nutrition 0.000 claims description 11
- 235000018977 lysine Nutrition 0.000 claims description 11
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 11
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 11
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 10
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 8
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
- 235000004279 alanine Nutrition 0.000 claims description 6
- 235000003704 aspartic acid Nutrition 0.000 claims description 6
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 6
- 235000013922 glutamic acid Nutrition 0.000 claims description 6
- 239000004220 glutamic acid Substances 0.000 claims description 6
- 235000004400 serine Nutrition 0.000 claims description 6
- 230000017531 blood circulation Effects 0.000 description 40
- 230000000694 effects Effects 0.000 description 21
- 230000035622 drinking Effects 0.000 description 19
- 230000037406 food intake Effects 0.000 description 14
- 229960003136 leucine Drugs 0.000 description 13
- 229960004295 valine Drugs 0.000 description 13
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 12
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 11
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 11
- 229960002885 histidine Drugs 0.000 description 11
- 229960003646 lysine Drugs 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 229960005190 phenylalanine Drugs 0.000 description 11
- 229960002429 proline Drugs 0.000 description 11
- 229960004799 tryptophan Drugs 0.000 description 11
- 229960003121 arginine Drugs 0.000 description 10
- 229960004441 tyrosine Drugs 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 9
- 229960004452 methionine Drugs 0.000 description 9
- 239000004473 Threonine Substances 0.000 description 8
- 229960002898 threonine Drugs 0.000 description 8
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 7
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 7
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 7
- 235000013361 beverage Nutrition 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 229960002449 glycine Drugs 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 102100030840 AT-rich interactive domain-containing protein 4B Human genes 0.000 description 5
- 101000792935 Homo sapiens AT-rich interactive domain-containing protein 4B Proteins 0.000 description 5
- 229960003767 alanine Drugs 0.000 description 5
- 229960005261 aspartic acid Drugs 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 229960001153 serine Drugs 0.000 description 5
- 235000021419 vinegar Nutrition 0.000 description 5
- 239000000052 vinegar Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000013365 dairy product Nutrition 0.000 description 3
- 229960002897 heparin Drugs 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 208000019838 Blood disease Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 229930064664 L-arginine Natural products 0.000 description 2
- 235000014852 L-arginine Nutrition 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 229930182844 L-isoleucine Natural products 0.000 description 2
- 239000004395 L-leucine Substances 0.000 description 2
- 235000019454 L-leucine Nutrition 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 208000014951 hematologic disease Diseases 0.000 description 2
- 208000018706 hematopoietic system disease Diseases 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000008234 soft water Substances 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 206010016326 Feeling cold Diseases 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010051151 Hyperviscosity syndrome Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000002788 crimping Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000002554 disease preventive effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960005337 lysine hydrochloride Drugs 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- -1 troche Substances 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
Images
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
- 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
- A61K31/33—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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
血管内の血液の流れやすさは、もちろん血管の収縮にも影響されるが、血液自体の流体としての特性に大きく影響される。血液は赤血球、白血球、血小板といった血球成分と、さまざまなタンパク質や脂質、無機質などが含まれている血しょう成分とに分けることができる。血液の流動性、言い換えれば血液の粘度は、特に赤血球の容積や変形能(しなやかに変形して狭いところを通過する能力)、血しょうフィブリノーゲン、白血球、血小板などの影響が大きいと考えられている。現在は採取した血液の流動性を測定する装置(MC-FAN:Micro Channel array Flow Analyzer)が開発されており、これにより、血液の流動性を測定することができる(非特許文献1〜3)。
血液流動性に影響を与える化合物及び/又は組成物について研究開発されている。例えば、果実酸サプリメントを長距離走行途中で摂取すると、更に走行し続けたときの血液粘性の上昇が抑制されたことが報告されている(非特許文献4)。
血液粘度は心臓血管系疾患に対する危険因子であるとされている。動脈系では、血液粘度が増すと、組織への血流量を維持するために血圧が上昇する。静脈系では、血液粘度の増大に伴い、血流量が減れば、ズリ速度が低下するので血液粘度が増して一層血流量が減る。このように血液粘度の上昇によって引き起こされる循環障害を過粘性症候群(hyperviscosity syndrome)といい、さまざまな疾患の底辺に横たわっていることが多いといわれている(日本生理学雑誌、第66巻、pp.234-244)。
上記のように、血液粘度は心臓血管系疾患など種々の疾患に対する危険因子であるから、近年増大する傾向にある心臓血管系疾患をはじめとする、これら疾患の治療及び/又は予防のためには、血液粘度を低下させる組成物又は血液流動性を改善させる組成物の開発は有用である。血液粘度が増大する要因としては、赤血球の形態変形能を低下、赤血球集合のなどが挙げられる。例えば、赤血球内のCaの蓄積とこれに起因する膜タンパク質間相互作用の変化は、本態性高血圧症の一因であるといわれている。他方、血液粘度を低下させる要因として例えば、NO生成物質が赤血球変形能を増大させるといわれている(日本生理学雑誌、第66巻、No.9、pp.287-297)。また、前記のように、果実酸や黒酢を摂取することにより、スポーツ選手のスポーツ中での血液粘性が低下することが報告されている。
本願発明には、スレオニン、プロリン、グリシン、バリン、イソロイシン、ロイシン、チロシン、フェニルアラニン、リジン、メチオニン、トリプトファン、ヒスチジン及びアルギニンを含むアミノ酸組成物を有効成分として含有する血液流動性改善剤又は血液粘度低下剤を包含する。
本願発明のアミノ酸組成物の使用形態は特に限定されないが、医療用としても、飲食用、栄養補助飲食用としても用いることができる。
試料としてアミノ酸飲料(VAAM、190g、明治乳業(株))を用い、プラセボとして水(190 g)を用いた。アミノ酸飲料1には、アミノ酸として、AspNa・H2Oが7mg、Thrが207mg、Serが63mg、Gluが114mg、Glyが347mg、Alaが132mg、Valが166mg、Metが19mg、Ileが143mg、Leuが196mg、Tyrが208mg、Pheが153mg、Trpが109mg、LysHClが382mg、Hisが97mg、Argが149mg、及びProが503mgで含有されている。
10名の被験者についてアミノ酸飲料(VAAM)の血流改善効果を評価した。その結果、8名において血流時間は短縮し、残りの2名では変化が見られなかった(図2)。プラセボ群の3名において血流時間の変化は認められなかったが、1名において大幅な延長が認められた。この1名については明らかにイレギュラーな測定値だと考えるのが妥当である。飲料摂取前の100μlの血流時間は45.4±4.4秒(mean±S.D.)であったのに対して、摂取1時間後では41.6±3.2秒であり、有意に短縮された(student’s t-検定)(図3)。他方、水飲用では血液流動性に影響を及ぼさなかった。つまり、アミノ酸飲料(VAAM)の単回摂取により認められた血流改善効果は、VAAMの有効成分となるアミノ酸混合物によるものだと推察できる。
試料としてアミノ酸混合物(VAAM Mix.)(3.0 g、明治乳業(株))を用いた。VAAM Mix.には、アミノ酸としてAspが7mg、Thrが207mg、Serが63mg、Gluが114mg、Glyが347mg、Alaが132mg、Valが166mg、Metが19mg、Ileが143mg、Leuが196mg、Tyrが208mg、Pheが153mg、Trpが109mg、LysHClが382mg、Hisが97mg、Argが149mg、及びProが503mgで含有されている。これを、オブラート(ピップトウキョウ(株)製)に包んで、50gの軟水で6名の被験者に飲用させた。VAAM Mix.の組成(重量%)は表1のとおりである。
BCAAを飲用した場合、4名の被験者において血流時間は短縮し、2名において延長した(図6)。試料摂取前の100μlの血流時間は41.1±2.7秒であったのに対して、摂取1時間後では39.8±2.4秒であり、血流時間に有意差は認められなかった(図7)。
Claims (2)
- アミノ酸組成物であって、スレニオンを2〜15モル、プロリンを4〜30モル、グリシンを7〜20モル、バリンを4〜8モル、イソロイシンを3〜9モル、ロイシンを2〜12モル、チロシンを1〜9モル、フェニルアラニンを0.5〜5モル、リジンを5〜11モルの割合で含有し、かつそれぞれ5モル以下の割合で、メチオニン、トリプトファン、ヒスチジン、アルギニンを含有し、更に1モル以下の割合のアスパラギン酸、5モル以下の割合のセリン、4モル以下の割合のグルタミン酸、12モル以下の割合のアラニンを含むことを特徴とする血液流動性改善剤又は血液粘度低下剤。
- 請求項1記載のアミノ酸組成物を1回に0.5〜5g投与することを特徴とする血液流動性改善剤又は血液粘度低下剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008520586A JP5764281B2 (ja) | 2006-06-08 | 2007-06-05 | 血液流動性改善剤 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006159901 | 2006-06-08 | ||
JP2006159901 | 2006-06-08 | ||
JP2008520586A JP5764281B2 (ja) | 2006-06-08 | 2007-06-05 | 血液流動性改善剤 |
PCT/JP2007/061364 WO2007142231A1 (ja) | 2006-06-08 | 2007-06-05 | 血液流動性改善剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2007142231A1 JPWO2007142231A1 (ja) | 2009-10-29 |
JP5764281B2 true JP5764281B2 (ja) | 2015-08-19 |
Family
ID=38801482
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008520586A Active JP5764281B2 (ja) | 2006-06-08 | 2007-06-05 | 血液流動性改善剤 |
Country Status (2)
Country | Link |
---|---|
JP (1) | JP5764281B2 (ja) |
WO (1) | WO2007142231A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010041647A1 (ja) * | 2008-10-06 | 2010-04-15 | 明治乳業株式会社 | アミノ酸組成物を有効成分として含む持久力向上剤、疲労防止剤、又は疲労回復剤 |
JP6774065B2 (ja) * | 2019-04-19 | 2020-10-21 | 株式会社東洋新薬 | 血流改善剤 |
Citations (5)
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 |
JP2518692B2 (ja) * | 1989-06-14 | 1996-07-24 | 理化学研究所 | 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 |
JP2003128560A (ja) * | 2001-10-23 | 2003-05-08 | Kikkoman Corp | 血液流動性改善剤 |
JP2004123707A (ja) * | 2002-07-29 | 2004-04-22 | Toyo Shinyaku:Kk | 血流改善組成物 |
JP2005272410A (ja) * | 2004-03-26 | 2005-10-06 | Ajinomoto Co Inc | 抗動脈硬化用及び/又は血液レオロジー改善用経口アミノ酸組成物 |
-
2007
- 2007-06-05 WO PCT/JP2007/061364 patent/WO2007142231A1/ja active Application Filing
- 2007-06-05 JP JP2008520586A patent/JP5764281B2/ja active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2518692B2 (ja) * | 1989-06-14 | 1996-07-24 | 理化学研究所 | 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 |
JPH0624977A (ja) * | 1992-07-10 | 1994-02-01 | Rikagaku Kenkyusho | 抗肥満剤及び抗高脂血症剤 |
JP2003128560A (ja) * | 2001-10-23 | 2003-05-08 | Kikkoman Corp | 血液流動性改善剤 |
JP2004123707A (ja) * | 2002-07-29 | 2004-04-22 | Toyo Shinyaku:Kk | 血流改善組成物 |
JP2005272410A (ja) * | 2004-03-26 | 2005-10-06 | Ajinomoto Co Inc | 抗動脈硬化用及び/又は血液レオロジー改善用経口アミノ酸組成物 |
Non-Patent Citations (1)
Title |
---|
JPN6012047947; Walter R, et al.: 'Pharmacological Concentrations of Arginine Influence Human Whole Blood Viscosity Independent of Nitr' Biochemical and Biophysical Research Communications Vol. 269, No. 3, 20000324, p. 687-691 * |
Also Published As
Publication number | Publication date |
---|---|
WO2007142231A1 (ja) | 2007-12-13 |
JPWO2007142231A1 (ja) | 2009-10-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Morlion et al. | Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study | |
TWI780096B (zh) | 胺基酸組合物及肌肉疾病與病症之治療方法 | |
US10660870B2 (en) | Compositions and methods for the treatment of liver diseases and disorders associated with one or both of hyperammonemia or muscle wasting | |
Ishida et al. | Effect of an excess intake of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro in subjects with normal blood pressure, high-normal blood pressure, or mild hypertension | |
Rasmussen et al. | Oral and intravenously administered amino acids produce similar effects on muscle protein synthesis in the elderly | |
JPH0624977A (ja) | 抗肥満剤及び抗高脂血症剤 | |
JPH04112825A (ja) | 脂質代謝調節剤 | |
JP5939550B2 (ja) | 酸化型アルブミン低下剤 | |
JP5764281B2 (ja) | 血液流動性改善剤 | |
KR20050072096A (ko) | 중추신경 기능 개선용 아미노산 조성물 | |
Nakasaki et al. | Complication of parenteral nutrition composed of essential amino acids and histidine in adults with renal failure | |
JP2002003372A (ja) | 造血および栄養状態改善用アミノ酸組成物 | |
ES2546619T3 (es) | Composición útil para la prevención de la diabetes tipo 2 y sus complicaciones en pacientes pre-diabéticos con resistencia a la insulina | |
JPH06336432A (ja) | アドレナリン及びノルアドレナリン分泌促進組成物 | |
US20150202181A1 (en) | Method of and compounds for the reduction of alcoholic hangover | |
US10426813B2 (en) | Method to enhance endurance | |
JP2002275059A (ja) | 腎機能障害改善用アミノ酸組成物 | |
TW202315605A (zh) | 用於治療covid—19急性後期後遺症的胺基酸組合物及方法 | |
KR20040071350A (ko) | 지구성 운동시 피로억제 및 운동 수행 후 면역기능 향상을위한 약학적 조성물 또는 기능성 식품 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100427 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120911 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121112 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130205 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130507 |
|
A911 | Transfer of reconsideration by examiner before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20130701 |
|
A912 | Removal of reconsideration by examiner before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20130719 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150615 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5764281 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |