CN102935231A - 使用瓜氨酸的治疗 - Google Patents
使用瓜氨酸的治疗 Download PDFInfo
- Publication number
- CN102935231A CN102935231A CN2012103324817A CN201210332481A CN102935231A CN 102935231 A CN102935231 A CN 102935231A CN 2012103324817 A CN2012103324817 A CN 2012103324817A CN 201210332481 A CN201210332481 A CN 201210332481A CN 102935231 A CN102935231 A CN 102935231A
- Authority
- CN
- China
- Prior art keywords
- arginine
- purposes
- cit
- citrulline
- orn
- 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.)
- Pending
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 23
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 title abstract description 44
- 229960002173 citrulline Drugs 0.000 title abstract description 43
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 title abstract description 42
- 235000013477 citrulline Nutrition 0.000 title abstract description 42
- 239000004475 Arginine Substances 0.000 claims abstract description 51
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 51
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 241000124008 Mammalia Species 0.000 claims description 11
- 238000000502 dialysis Methods 0.000 claims description 11
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 210000003734 kidney Anatomy 0.000 claims description 8
- 230000004060 metabolic process Effects 0.000 claims description 8
- 239000002243 precursor Substances 0.000 claims description 8
- 235000015872 dietary supplement Nutrition 0.000 claims description 7
- 230000029663 wound healing Effects 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 206010022489 Insulin Resistance Diseases 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 239000004202 carbamide Substances 0.000 claims description 4
- 235000013877 carbamide Nutrition 0.000 claims description 4
- 150000001720 carbohydrates Chemical class 0.000 claims description 4
- 206010061481 Renal injury Diseases 0.000 claims description 3
- 235000014633 carbohydrates Nutrition 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 230000008753 endothelial function Effects 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 239000000835 fiber Substances 0.000 claims description 3
- 229940088597 hormone Drugs 0.000 claims description 3
- 239000005556 hormone Substances 0.000 claims description 3
- 230000036737 immune function Effects 0.000 claims description 3
- 208000037806 kidney injury Diseases 0.000 claims description 3
- 230000028327 secretion Effects 0.000 claims description 3
- 230000006442 vascular tone Effects 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 235000010755 mineral Nutrition 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 3
- 230000003247 decreasing effect Effects 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 26
- 235000019640 taste Nutrition 0.000 abstract description 12
- 201000006549 dyspepsia Diseases 0.000 abstract description 9
- 230000001965 increasing effect Effects 0.000 abstract description 5
- 208000017667 Chronic Disease Diseases 0.000 abstract description 4
- 230000001154 acute effect Effects 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 4
- 239000008280 blood Substances 0.000 abstract description 4
- 208000030090 Acute Disease Diseases 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000009469 supplementation Effects 0.000 abstract description 3
- 230000001771 impaired effect Effects 0.000 abstract description 2
- 238000012423 maintenance Methods 0.000 abstract 2
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 230000036186 satiety Effects 0.000 abstract 1
- 235000019627 satiety Nutrition 0.000 abstract 1
- 235000009697 arginine Nutrition 0.000 description 46
- 229960003121 arginine Drugs 0.000 description 46
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 42
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 17
- 210000002784 stomach Anatomy 0.000 description 17
- 229930064664 L-arginine Natural products 0.000 description 16
- 235000014852 L-arginine Nutrition 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 12
- 210000002460 smooth muscle Anatomy 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 230000008901 benefit Effects 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 235000013305 food Nutrition 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 229960003753 nitric oxide Drugs 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 206010040047 Sepsis Diseases 0.000 description 5
- 235000019658 bitter taste Nutrition 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- 235000016709 nutrition Nutrition 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000035764 nutrition Effects 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 3
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 3
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 235000013367 dietary fats Nutrition 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000021542 oral nutrition Nutrition 0.000 description 3
- 229960003104 ornithine Drugs 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- 102000004452 Arginase Human genes 0.000 description 2
- 108700024123 Arginases Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 210000002249 digestive system Anatomy 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001071 malnutrition Effects 0.000 description 2
- 235000000824 malnutrition Nutrition 0.000 description 2
- 210000000412 mechanoreceptor Anatomy 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 108091008709 muscle spindles Proteins 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 208000015380 nutritional deficiency disease Diseases 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004648 relaxation of smooth muscle Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 description 1
- KDZOASGQNOPSCU-WDSKDSINSA-N Argininosuccinic acid Chemical compound OC(=O)[C@@H](N)CCC\N=C(/N)N[C@H](C(O)=O)CC(O)=O KDZOASGQNOPSCU-WDSKDSINSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 206010021703 Indifference Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 206010060926 abdominal symptom Diseases 0.000 description 1
- 230000004447 accommodation reflex Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000007882 dietary composition Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
- 239000004226 guanylic acid Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 208000011316 hemodynamic instability Diseases 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000009635 nitrosylation Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000009894 physiological stress Effects 0.000 description 1
- 208000022530 polyphagia Diseases 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
- 210000001187 pylorus Anatomy 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000004514 sphincter of oddi Anatomy 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Hematology (AREA)
- Food Science & Technology (AREA)
- Mycology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Polymers & Plastics (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
Abstract
本发明提供用于治疗或维持状况的方法和制剂,所述状况将受益于在血液中增加或维持精氨酸的水平,并具有优于目前精氨酸补充(supplementation)的改善的味道特征。此外,血液中精氨酸水平的这种维持在精氨酸到瓜氨酸产生速率受损的急性和慢性疾病中将是有益的。此外本发明提供在个体中治疗饱食和消化不良至少一种的方法。在一个实施方案中,本方法包括向个体施用有效量的L-瓜氨酸。
Description
本申请是申请日为2007年4月2日、发明名称为“使用瓜氨酸的治疗”的中国专利申请200780012356.5(国际申请号PCT/US2007/008143)的分案申请。
发明背景
1.技术背景
本发明涉及病症的治疗或维持,其将受益于血液中精氨酸水平的增加或维持,并具有优于目前精氨酸补充给药(supplementation)的改善的味觉特征。此外本发明通常涉及早饱的治疗,并且更具体而言,涉及L-瓜氨酸的施用以促进胃平滑肌的松弛。此外,本发明通常在透析开始前或接受透析或在这两个过程中施用所述瓜氨酸时将使用瓜氨酸与肾损伤患者中增强的创伤愈合和改善的微循环的益处联系起来。
2.背景知识
早饱是在消耗足够卡路里和/或液体之前的发胀感。消化不良是特征为慢性或复发性上腹症状的消化系统紊乱,包括摄取食物后早饱、不舒适、胃灼热和/或恶心。急性或长时间的早饱或消化不良可能导致营养不良和/或脱水。某些个体,如癌症患者、患有慢性病如人免疫缺陷病毒(HIV)的那些个体和老年人经常经受早饱和/或消化不良。因此这些个体更可能会经受卡路里或液体摄入量不足,其可能使目前的健康问题进一步复杂化。
治疗早饱和消化不良的已知方法通常集中在刺激个体食欲或施用低量、富含营养和卡路里的膳食补充物上。两种方法均不能令人满意。增加经受早饱或营养不良的个体的食欲只增加了所述个体在感觉到饱或消化不良症状发作后将继续进食的可能性,经常引起强烈不适。富含营养和卡路里的膳食补充物通常不如个体的正常饮食可口,并因此更不可能以缓和早饱或消化不良引起的营养不良和/或脱水效应所必需的量进行消耗。
胃部肌肉通过刺激牵张和营养物感受器提供反馈给大脑。当胃因摄入食物而膨胀时,牵张感受器在胃部肌肉中被激活,触发迷走神经中的抑制信号,导致停止进食的要求。此类膨胀在胃底的调节反射中特别明显。如果胃部肌肉舒张,特别是胃底的那些肌肉,饱食感会减少,其允许个体在达到饱食前消耗更多食物。因此,胃部平滑肌的舒张预防早饱,在牵张感受器激活前增加胃中存在的食物量。
治疗早饱的其它方法因此已集中在平滑肌的舒张上。胃部平滑肌舒张的生化机制是已知的。一氧化氮(NO)通过与蛋白质中的金属离子或半胱氨酸中的硫原子相互作用结合到细胞蛋白质受体(例如鸟苷酸环化酶)上。NO的结合引起蛋白质的改变,其依次引起第二信使环鸟苷酸(cGMP)浓度的升高。cGMP引起平滑肌舒张,如食道下端括约肌、胃底、幽门、奥狄括约肌、肠和肛门的舒张。因此,NO的增加将导致平滑肌的增强舒张,包括胃部平滑肌,特别是胃底的平滑肌。
NO的原始来源是氨基酸精氨酸。通过酶一氧化氮合酶(NOS)使精氨酸代谢成为瓜氨酸和NO。因此,通过胃部肌肉舒张治疗早饱的方法可能包括精氨酸的增加消耗。然而,该方法的困难是仅部分的个体消耗的精氨酸保留可用于代谢成为NO。高达60%的摄入精氨酸进入循环前在肝脏中通过精氨酸酶代被谢掉,在所述循环中任何剩余的精氨酸可以代谢成为瓜氨酸和NO。因此,此方法将需要摄取大量富含精氨酸的膳食补充物来诱导胃部肌肉的舒张。如此大量的膳食补充物自身将引起饱食效应,抵消由后续NO产生所造成的任何舒张效应。精氨酸的备选来源是从氨基酸瓜氨酸内源产生精氨酸。该途径贡献了约20%的整体精氨酸产量。瓜氨酸在肠中产生且不经肝脏代谢进入循环,在肾中几乎完全转化成精氨酸。
在此程度上,存在对于治疗早饱方法的需要,其不用遭受以上缺陷。
此外,在口服营养组合物中使用某些食用氨基酸,包括L-精氨酸,在碱性pH值时具有令人不快的味道。在L-精氨酸的情况下这是其碱性侧链的直接结果。美国专利申请20020193342Hamman&Calton(2002)“Modifying undesirable tastes”描述了使用三氯蔗糖来掩盖游离氨基酸味道。美国专利5780039Greenberg等人(1998)描述了口服营养组合物精氨酸的改善味道和脂肪酸的胶囊化。美国专利申请20020068365 Kuhrts(2002)使用具有80%L-精氨酸和20%包衣的小包被颗粒剂。包衣提供了对苦味L-精氨酸的味道掩盖并产生了缓释的粉状饮料混合物。前述方法,虽然在掩盖味道上有些效果,但是仍然存在L-精氨酸味道的潜在问题。
发明概述
本发明提供在个体中治疗至少一种饱食和消化不良的方法。在一个实施方案中,所述方法包括向个体施用有效量的L-瓜氨酸。
本发明的第一个方面提供在个体中治疗至少一种饱食和消化不良的方法,所述方法包括:增加个体细胞中的一氧化氮(NO)的浓度,其中NO浓度增加导致胃部平滑肌的舒张。
本发明的第二个方面提供经口施用的营养补充物,其包含:有效引起个体细胞中一氧化氮(NO)浓度增加的L-瓜氨酸的量。
本发明的第三方面是改善含有碱性氨基酸L-精氨酸苦味的组合物的味道。通常通过加入酸如磷酸来平衡溶液的pH,但是该额外的酸可能增加饮料稳定性的问题。然而,用L-瓜氨酸完全或部分替换L-精氨酸导致更中性pH的饮料,其不需要补充酸(例如,磷酸)来平衡pH。
本发明的第四方面是使用L-瓜氨酸或L-鸟氨酸的口服补充来增加或维持血液中精氨酸水平的有效机制。精氨酸在体内具有许多功效,其包括免疫功能、创伤愈合、激素分泌、血管紧张度、胰岛素敏感性和内皮功能的调节。使用瓜氨酸维持精氨酸水平将导致类似的益处涵盖于本发明的范围内。
本发明的第五个方面是在哺乳动物,尤其是在人类中治疗或预防急性或慢性疾病的有效机制,所述疾病的特征在于比正常瓜氨酸到精氨酸的转化率低,所述有效机制包含至少一种瓜氨酸或瓜氨酸的前体,其用于所述哺乳动物的每日剂量至少是瓜氨酸到精氨酸转化率降低的量。
本发明的第六个方面是瓜氨酸对于在透析开始前或接受透析时或在两个过程中施用时在肾脏损伤患者中增加的创伤愈合和改善的微循环的益处的用途。这至少部分通过哺乳动物减少的尿素和/或氨产生来实现。
设计本发明的说明性方面来解决此处描述的问题和未讨论的其它问题,其为技术人员可发现的。
详细描述
如上指出,本发明提供在个体中治疗早饱和/或消化不良的方法。本发明还提供用于此类治疗的产品。
如此处所用,术语“治疗”的各种词性形式(“treatment”、“treating”和“treat”)指预防性或防止性治疗和治愈或疾病缓和治疗,包括治疗处于正在感染有疾病或疑似已感染有疾病风险中的患者,及生病或已诊断为患有疾病或医学状况(medical condition)的患者。术语“治疗”的各种词性形式也指维持和/或促进未患病但可能对不健康状态如早饱或消化不良的发展敏感的个体健康。因此,“有效量”是这样的量,其在个体中治疗疾病或医学状况,或更普遍地向个体提供营养、生理学或医学益处。
如此处所用,哺乳动物包括但不局限于啮齿类动物、水生哺乳动物、家畜如犬和猫、农场动物如绵羊、猪、牛和马,以及人类。其中使用术语哺乳动物,考虑它也应用于其它动物,所述动物能够产生哺乳动物展现出的或旨在展现出的效应。
如上描述,精氨酸像大多数氨基酸一样在进入循环系统前主要在肝脏中进行代谢。这限制了精氨酸作为一氧化氮(NO)的来源用于平滑肌舒张的用途。
然而,少数氨基酸经过肝脏时很少或没有代谢。一种此类氨基酸是L-瓜氨酸,精氨酸的前体。正如精氨酸可以转化为瓜氨酸和NO,L-瓜氨酸在线粒体中可以转化为精氨酸。大多数循环的L-瓜氨酸在包含高度代谢活性组织的肾脏中进行转化。如此,血流中循环的L-瓜氨酸首先转化为精氨酸,然后在细胞中转化为瓜氨酸和NO。
值得注意的是,L-瓜氨酸到精氨酸的转化持续发生,只要L-瓜氨酸在血流中循环。因此,循环的L-瓜氨酸使在一段时间内维持精氨酸的升高浓度成为可能,其依次使得维持细胞中NO的稳定释放成为可能,这引起胃部肌肉的舒张和早饱的减缓或避免。至少某些情况的消化不良与消化系统平滑肌,尤其是胃部平滑肌的收缩相关。因此,L-瓜氨酸的施用也可用于治疗消化不良。
根据本发明,可以通过本领域具有普通技能的技术人员了解的任何方法向个体施用有效量的L-瓜氨酸。在一个实施方案中,在经口施用的营养补充物中向个体施用有效量的L-瓜氨酸。根据本发明的补充物可以进一步包含对个体提供营养、生理学或医学益处的任何数量的成分。此类成分包括,例如蛋白质、可溶和/或不可溶的纤维、脂肪酸、维生素、矿物质、糖类和/或其它碳水化合物、调味剂,以及药物或其它治疗剂。
在口服营养组合物中使用某些膳食氨基酸,包括L-精氨酸在碱性pH时具有令人不快的味道。在L-精氨酸的情况下是其碱性侧链的直接结果。为了改善口服组合物的味道,通过加入酸(低pH)中和组合物的高/碱性pH。较高的酸度通过减少与碱性氨基酸(例如,L-精氨酸)相关的苦味也改善这些组合物的味道。
当在营养组合物中使用酸时会产生额外的问题。例如,经常使用磷酸,但导致组合物的磷含量升高。氨基酸L-瓜氨酸是L-精氨酸的前体。结果,我们提出在营养组合物中L-瓜氨酸可以代替L-精氨酸。不像精氨酸,瓜氨酸通过从饮食中吸收或从头在肠中产生进入血流后不经肝脏进行代谢。瓜氨酸经尿素循环的部分通过线粒体酶促转化为精氨酸。
因为瓜氨酸的使用消除了对使用酸中和pH并且抵消由碱性氨基酸L-精氨酸引起的苦味的需要,因此将膳食脂肪包括进营养组合物中变得更容易。将膳食脂肪加入到具有非常高或低pH的组合物中是个重大挑战。结果,提出瓜氨酸是膳食组合物中对精氨酸的可行的备选,因为它增加了制剂中的选择。结果,使用瓜氨酸的益处包括酸的减少和将膳食脂类掺进组合物中改善组合物营养价值的能力。
向具有非常高或低pH的组合物中加入膳食脂肪是个重大挑战。含L-精氨酸的液体营养组合物需要包含酸来抵消由L-精氨酸的碱性pH产生的苦味。用L-瓜氨酸完全或部分地代替L-精氨酸分别消除或减少了组合物中对大量酸的需要。
本发明的另一方面是适合于在哺乳动物,尤其是在人类中治疗或预防急性或慢性疾病的组合物,所述疾病的特征在于比正常瓜氨酸到精氨酸的转化率低,所述组合物其包含至少一种瓜氨酸或瓜氨酸的前体,其用于所述哺乳动物的每日剂量至少是瓜氨酸向精氨酸转化率降低的量。
精氨酸缺乏可以在外科手术或其它创伤的数小时内发生,作为对施加在身体上的创伤的生理改变的结果。缺乏也可以在脓毒症过程中发生。精氨酸缺乏至少部分是由精氨酸酶酶活性增加从而精氨酸活性增加引起。
瓜氨酸可以以口服和肠内产品经胃肠道给出。瓜氨酸内源是肠内谷氨酰胺的代谢产物,作为尿素循环的部分从鸟氨酸产生,并通过体内分布的一氧化氮合酶形成。精氨酸主要在肾脏中经由通过精氨琥珀酸合酶(EC6.3.4.5)和精氨琥珀酸裂合酶(EC4.3.2.1)的瓜氨酸代谢,从瓜氨酸产生。
已认为脓毒症患者精氨酸缺乏(从瓜氨酸产生精氨酸减少的结果)并且还饮食摄取也不足。这已经导致使用富含精氨酸的肠配方。精氨酸是已知血管舒张剂一氧化氮的前体。因为预期的血流动力学不稳定性及蛋白质的亚硝基化,已经认为由于输注精氨酸而增强的一氧化氮产生是有害的。因此,在严重脓毒症患者中长时间持续静脉精氨酸的补充(作为单一组分)过程中研究这些效应。
实施例1:
方法:按照安慰剂对照的双盲研究设计,将严重脓毒症/脓毒性休克(<48小时;APACHEⅡ分值介于18-41)的ICU患者随机分至经静脉72小时L-精氨酸-HCl(1.2μmol/kg.min,n=9)或等能的L-丙氨酸(安慰剂;n=9)处理组中。研究起始在0.08-0.9g/kg.min范围内用去甲肾上腺素处理所有患者。整个方案中以2小时间隔记录血液动力学。在基线并以24小时间隔对血液取样并分析血浆硝化酪氨酸水平。使用重复测量ANOVA;数据为平均值±SEM。
结果:用精氨酸或安慰剂处理的患者之间血浆硝化酪氨酸无差别(对于比较,正常值为约1nM)。两组间未观测到全身血压和去甲肾上腺素剂量的显著差异。
PLAC,安慰剂;ARG,精氨酸处理。重复测量ANOVA:T,时间效应。
结论:输注精氨酸不增强对血浆蛋白质的氧化效应且不影响全身血压。因此在严重脓毒症患者中不存在精氨酸对氧化应激或血液动力学状态的有害效应。因此,瓜氨酸施用导致对精氨酸缺乏的矫正,在某些情况下可能升高精氨酸水平至高于确定的正常水平,理论认为这种升高是机体在某些生理应激情况下实现过度需求的方式。由于不认为机体将瓜氨酸过度地转化为精氨酸,所以认为这些水平是安全的。
近期研究已显示在血液透析患者中精氨酸水平在透析进行前和进行后均升高(Chuang等人,Clinica Chimica Acta364;216,2006)。瓜氨酸也在透析进行前和进行后升高。然而,在相同透析处理过程中精氨酸水平降低36%而瓜氨酸水平降低258%。瓜氨酸这一更大程度的降低提出对透析患者使用瓜氨酸作为精氨酸替代物的可能性,所述患者由于糖尿病和缺乏流动性而需要改善创伤愈合。
已显示过量的精氨酸导致肾脏受损患者额外的肾脏问题(Efron和Barbul,J.Renal Nutr.9(3)142,1999)。瓜氨酸可经体内转化用于提供精氨酸。此外,瓜氨酸比精氨酸少一个氨基。这降低了所产生氨和尿素的量并减少对已受损肾脏的压力。
因此,使用瓜氨酸替代精氨酸可在透析开始前及接受透析过程中对肾脏损伤患者中的创伤愈合和微循环有增加的益处。
在本发明的另一方面,精氨酸在体内具有很多功效,包括免疫功能、创伤愈合、激素分泌、血管紧张度、胰岛素敏感性、和内皮功能的调节。使用瓜氨酸维持精氨酸水平将产生类似的益处涵盖于本发明的范围内。
以上对本发明多种方面的描述已展示用于说明和描述目的。不旨在彻底描述或限制本发明至公开的准确形式,且显然,许多修改和变化是可能的。可能对本领域技术人员明显的此类修改和变化意图包含于所附权利要求定义的本发明范围中。
Claims (11)
1.包含L-瓜氨酸或L-鸟氨酸、L-瓜氨酸或L-鸟氨酸的前体或盐,或其组合的组合物用于制备药物的用途,所述药物用于治疗或调节哺乳动物中的免疫功能、创伤愈合、激素分泌、血管紧张度、胰岛素敏感性和内皮功能。
2.根据权利要求1的用途,其中所述哺乳动物是人。
3.根据权利要求1的用途,其中所述L-瓜氨酸或L-鸟氨酸、L-瓜氨酸或L-鸟氨酸的前体或盐,或其组合调节胰岛素敏感性。
4.权利要求1的用途,其中至少部分量的L-瓜氨酸或L-鸟氨酸、L-瓜氨酸或L-鸟氨酸的前体或盐,或其组合被代谢形成精氨酸。
5.根据权利要求1的用途,其中所述哺乳动物是肾脏损伤的。
6.根据权利要求5的用途,其中在透析开始前或接受透析时,或透析开始前和接受透析时向哺乳动物施用所述药物。
7.根据权利要求6的用途,其中由所述哺乳动物产生的氨或尿素或者氨和尿素的量减少。
8.根据权利要求6的用途,其中对肾脏的压力降低。
9.根据权利要求1的用途,其中所述药物为经口施用的营养补充物的形式。
10.根据权利要求9的用途,其中所述组合物还包括以下中的至少一种:蛋白质、可溶纤维、不可溶纤维、脂肪酸、维生素、矿物质、碳水化合物、调味剂、药物和治疗剂。
11.根据权利要求10的用途,其中所述碳水化合物包含至少一种糖。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US78933006P | 2006-04-04 | 2006-04-04 | |
US60/789,330 | 2006-04-04 | ||
US74749306P | 2006-05-17 | 2006-05-17 | |
US60/747,493 | 2006-05-17 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200780012356.5A Division CN101415414B (zh) | 2006-04-04 | 2007-04-02 | 瓜氨酸在制备治疗矫正脓毒症患者中精氨酸缺乏的药物中的用途 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN102935231A true CN102935231A (zh) | 2013-02-20 |
Family
ID=38461725
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2012103324817A Pending CN102935231A (zh) | 2006-04-04 | 2007-04-02 | 使用瓜氨酸的治疗 |
Country Status (13)
Country | Link |
---|---|
US (1) | US20090291877A1 (zh) |
EP (3) | EP2679223A1 (zh) |
JP (2) | JP2009533342A (zh) |
CN (1) | CN102935231A (zh) |
AU (1) | AU2007233371B2 (zh) |
BR (1) | BRPI0710044A2 (zh) |
CA (2) | CA2778823A1 (zh) |
HK (1) | HK1126390A1 (zh) |
IL (1) | IL194202A0 (zh) |
MX (1) | MX2008012723A (zh) |
RU (1) | RU2444355C2 (zh) |
WO (1) | WO2007114903A2 (zh) |
ZA (1) | ZA200809393B (zh) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2913885B1 (fr) * | 2007-03-22 | 2012-07-20 | Univ Paris Descartes | Utilisation de la citrulline pour le traitement des pathologies liees a une augmentation de la carbonylation des proteines |
EP3320895B1 (en) | 2007-10-10 | 2021-03-10 | Kyowa Hakko Bio Co., Ltd. | Rapid-acting, blood-arginine-level-increasable oral preparation comprising citrulline and arginine |
ITMI20080567A1 (it) * | 2008-04-02 | 2009-10-03 | Androsystems Srl | L-citrullina per il trattamento della disfunzione endoteliale e della disfunzione erettile. |
MX2011002982A (es) | 2008-09-19 | 2011-04-11 | Nestec Sa | Soporte nutricional del sistema inmunologico durante el tratamiento anti-cancer. |
CA2736774C (en) * | 2008-09-19 | 2017-08-22 | Institut Curie | Nutritional support to prevent and/or mitigate bone marrow toxicity from a cancerous tumor |
US20100179089A1 (en) * | 2009-01-13 | 2010-07-15 | Deutz Nicolaas E P | Compositions and Methods to Manage the Inflammatory Basis of Chronic Disease Conditions and Maintain an Optimal Immune Response in Elderly |
EP2464246A2 (en) * | 2009-08-13 | 2012-06-20 | Nestec S.A. | Nutritional compositions including exogenous nucleotides |
FR2970414B1 (fr) * | 2011-01-14 | 2013-03-22 | Univ Paris Descartes | Action preventive de la citrulline sur le developpement spontane des tumeurs |
CN103491804A (zh) * | 2011-04-18 | 2014-01-01 | 雀巢产品技术援助有限公司 | 具有α-HICA 和二十碳五烯酸的营养组合物 |
JP2013060406A (ja) * | 2011-09-15 | 2013-04-04 | Kyowa Hakko Bio Co Ltd | 脳疲労改善用経口剤 |
US8691295B2 (en) * | 2011-10-26 | 2014-04-08 | John Michael Richards | Dietary supplement for vascular health |
US20150025147A1 (en) * | 2012-03-02 | 2015-01-22 | Kyowa Hakko Bio Co., Ltd | Enhancer for eating activity and/or gastrointestinal activity |
MX2017015664A (es) * | 2015-06-29 | 2018-04-18 | Univ Vanderbilt | Administracion intravenosa de citrulina durante cirugia. |
JP6357625B2 (ja) * | 2015-07-23 | 2018-07-18 | テクノサイエンス株式会社 | 栄養補助食品用の組成物 |
KR102396603B1 (ko) | 2015-09-16 | 2022-05-11 | 원광대학교산학협력단 | 시트룰린을 유효성분으로 함유하는 간 기능 개선용 조성물 |
JP2016121194A (ja) * | 2016-04-05 | 2016-07-07 | 協和発酵バイオ株式会社 | 脳疲労改善用経口剤 |
JP2018119017A (ja) * | 2018-05-16 | 2018-08-02 | テクノサイエンス株式会社 | 栄養補助食品用の組成物 |
EP4142520A1 (en) * | 2020-04-29 | 2023-03-08 | Société des Produits Nestlé S.A. | A nutritional product containing a buffer composition and an amino acid and methods of using such a nutritional product |
CN112868919B (zh) * | 2021-02-25 | 2023-01-17 | 新疆农业大学 | 一种提升公羊精液品质的饲料及其应用 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4096254A (en) * | 1976-05-10 | 1978-06-20 | Richardson-Merrell Inc. | Method of treating the symptoms of menopause and osteoporosis |
US5411757A (en) * | 1989-11-09 | 1995-05-02 | Buist; Neil R. M. | Palatable balanced amino acid-modified diet |
DE69228006T2 (de) * | 1991-09-27 | 1999-08-12 | Board of Regents, the University of Texas System, Austin, Tex. | Parenteral anzuwendende Aminosäuren enthaltende Zubereitungen zur Bekämpfung von Hypotension und verwandten Pathologien |
US5780039A (en) | 1992-04-23 | 1998-07-14 | Novartis Nutrition Ag | Orally-ingestible nutrition compositions having improved palatability |
US5356873A (en) * | 1992-11-05 | 1994-10-18 | Clintec Nutrition Co. | Method for providing nutritional requirements to patients having a chronic inflammation reaction |
US5874471A (en) * | 1997-02-27 | 1999-02-23 | Waugh; William Howard | Orthomolecular medical use of L-citrulline for vasoprotection, relaxative smooth muscle tone and cell protection |
US20010056068A1 (en) * | 1998-03-04 | 2001-12-27 | Kristof Chwalisz | Method of treatment and prevention of nitric oxide deficiency-related disorders with citrulline and citrulline derivatives |
US20020068365A1 (en) | 1998-07-28 | 2002-06-06 | Eric H. Kuhrts | Controlled release nitric oxide producing agents |
WO2000025776A1 (en) * | 1998-10-30 | 2000-05-11 | Nitromed, Inc. | Nitrosated and nitrosylated nonsteroidal antiinflammatory compounds, compositions and methods of use |
DK1010374T3 (da) * | 1998-12-15 | 2005-11-21 | Nestle Sa | Fiberblanding til enterale sammensætninger |
US20020193342A1 (en) | 2001-05-09 | 2002-12-19 | Hamman John P. | Modifying undesirable tastes |
AU2003254282A1 (en) * | 2002-08-01 | 2004-02-23 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
ATE354295T1 (de) * | 2002-12-06 | 2007-03-15 | Kyowa Hakko Kogyo Kk | Verfahren zur verringerung der bitterkeit von aminosäure |
FR2857262B1 (fr) * | 2003-07-08 | 2007-10-05 | Biocodex Lab | Utilisation de la citrulline dans le cadre de l'insuffisance intestinale |
WO2005107735A2 (en) * | 2004-04-30 | 2005-11-17 | Pump Formulations, Ltd. | Nutritional composition for enhancing lean muscle stimulus, growth, strength and recovery, creating and prolonging intense muscle pumps, supporting endurance, strength, performance, size and stamina, providing a transducer effect for nitric oxide, incresing nutrient delivery and/or promoting increased vascular response in a |
WO2006002096A2 (en) * | 2004-06-18 | 2006-01-05 | Vivo Therapeutics, Inc. | Low doses of l-citrulline for treating diseases |
US20060046982A1 (en) * | 2004-08-26 | 2006-03-02 | Waugh William H | Orthomolecular medical use of L-citrulline for capillary endothelial protection and adjacent cell protection in neurodegenerative disease |
-
2007
- 2007-04-02 AU AU2007233371A patent/AU2007233371B2/en not_active Ceased
- 2007-04-02 CA CA2778823A patent/CA2778823A1/en not_active Abandoned
- 2007-04-02 EP EP13175960.7A patent/EP2679223A1/en not_active Withdrawn
- 2007-04-02 CA CA2648126A patent/CA2648126C/en not_active Expired - Fee Related
- 2007-04-02 MX MX2008012723A patent/MX2008012723A/es not_active Application Discontinuation
- 2007-04-02 CN CN2012103324817A patent/CN102935231A/zh active Pending
- 2007-04-02 WO PCT/US2007/008143 patent/WO2007114903A2/en active Application Filing
- 2007-04-02 US US12/293,283 patent/US20090291877A1/en not_active Abandoned
- 2007-04-02 JP JP2009504245A patent/JP2009533342A/ja active Pending
- 2007-04-02 EP EP07754640A patent/EP2004171A2/en not_active Withdrawn
- 2007-04-02 RU RU2008143310/14A patent/RU2444355C2/ru not_active IP Right Cessation
- 2007-04-02 BR BRPI0710044-2A patent/BRPI0710044A2/pt not_active IP Right Cessation
- 2007-04-02 EP EP13150724.6A patent/EP2612666A3/en not_active Withdrawn
-
2008
- 2008-09-18 IL IL194202A patent/IL194202A0/en unknown
- 2008-11-03 ZA ZA2008/09393A patent/ZA200809393B/en unknown
-
2009
- 2009-05-26 HK HK09104767.4A patent/HK1126390A1/xx not_active IP Right Cessation
-
2012
- 2012-05-21 JP JP2012115906A patent/JP2012197283A/ja active Pending
Non-Patent Citations (2)
Title |
---|
M. M. HALLEMEESCH ET AL: "Reduced arginine availability and nitric oxide production", 《CLINICAL NUTRITION》 * |
TONE BC ET AL: "Cellular and physiological effects of arginine", 《MINI REV MED CHEM》 * |
Also Published As
Publication number | Publication date |
---|---|
MX2008012723A (es) | 2008-10-14 |
RU2008143310A (ru) | 2010-05-10 |
CA2648126A1 (en) | 2007-10-11 |
EP2679223A1 (en) | 2014-01-01 |
JP2009533342A (ja) | 2009-09-17 |
BRPI0710044A2 (pt) | 2011-08-02 |
AU2007233371A1 (en) | 2007-10-11 |
AU2007233371B2 (en) | 2012-11-29 |
EP2612666A2 (en) | 2013-07-10 |
RU2444355C2 (ru) | 2012-03-10 |
ZA200809393B (en) | 2009-12-30 |
WO2007114903A3 (en) | 2008-02-14 |
CA2648126C (en) | 2012-12-18 |
EP2612666A3 (en) | 2013-10-02 |
CA2778823A1 (en) | 2007-10-11 |
EP2004171A2 (en) | 2008-12-24 |
US20090291877A1 (en) | 2009-11-26 |
IL194202A0 (en) | 2009-09-22 |
HK1126390A1 (en) | 2009-09-04 |
WO2007114903A2 (en) | 2007-10-11 |
JP2012197283A (ja) | 2012-10-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102935231A (zh) | 使用瓜氨酸的治疗 | |
CN100355420C (zh) | 富含亮氨酸的营养组合物 | |
US6368617B1 (en) | Dietary supplement | |
ES2286238T3 (es) | Composicion para rehidratacion. | |
US20050287204A1 (en) | Nutritional or pharmaceutical compositions for increasing the creatine response of organisms | |
US20220240558A1 (en) | High-energy food supplement based on inverted sugars and ergogenic products for use in physical activity and method for producing same | |
US20210353671A1 (en) | Compositions comprising cinnamaldehyde and zinc and methods of using such compositions | |
JPS63287462A (ja) | ペプチド栄養剤 | |
CN101415414B (zh) | 瓜氨酸在制备治疗矫正脓毒症患者中精氨酸缺乏的药物中的用途 | |
US20140127323A1 (en) | Dietetic multi-component system | |
RU2335927C2 (ru) | Обогащенные лейцином питательные композиции | |
RU2720134C1 (ru) | Фармацевтическая композиция для парентерального капельного введения | |
US20240268433A1 (en) | Nutritional Compositions for Preserving Muscle Mass | |
EP3389666A1 (en) | Compositions comprising 3'-o-glucuronide epicatechin and methods of making and using such compositions | |
JP2000302677A (ja) | カルニチン自己産生能改善作用を有する医薬および食品・飼料組成物 | |
JP2001226285A (ja) | 小腸成長促進組成物 | |
Levin | Chronic Fatigue Syndrome: The Yeast Concept |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130220 |