CN104286456A - 控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法 - Google Patents
控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法 Download PDFInfo
- Publication number
- CN104286456A CN104286456A CN201410479815.2A CN201410479815A CN104286456A CN 104286456 A CN104286456 A CN 104286456A CN 201410479815 A CN201410479815 A CN 201410479815A CN 104286456 A CN104286456 A CN 104286456A
- Authority
- CN
- China
- Prior art keywords
- interleukin
- purposes
- lipoic acid
- dog
- inflammation
- 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
- 230000004054 inflammatory process Effects 0.000 title claims abstract description 17
- 206010061218 Inflammation Diseases 0.000 title claims abstract description 16
- 241001465754 Metazoa Species 0.000 title abstract description 15
- 238000000034 method Methods 0.000 title abstract description 11
- 230000004968 inflammatory condition Effects 0.000 title abstract 2
- 230000000116 mitigating effect Effects 0.000 title abstract 2
- 235000019136 lipoic acid Nutrition 0.000 claims abstract description 26
- 229960002663 thioctic acid Drugs 0.000 claims abstract description 22
- 235000005911 diet Nutrition 0.000 claims abstract description 16
- 230000037213 diet Effects 0.000 claims abstract description 15
- 206010003246 arthritis Diseases 0.000 claims abstract description 5
- 235000013305 food Nutrition 0.000 claims description 30
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 16
- 230000002757 inflammatory effect Effects 0.000 claims description 15
- 239000000090 biomarker Substances 0.000 claims description 14
- 230000014509 gene expression Effects 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 6
- AGBQKNBQESQNJD-ZETCQYMHSA-N (S)-lipoic acid Chemical compound OC(=O)CCCC[C@H]1CCSS1 AGBQKNBQESQNJD-ZETCQYMHSA-N 0.000 claims description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- 108010074328 Interferon-gamma Proteins 0.000 claims description 4
- 102000008070 Interferon-gamma Human genes 0.000 claims description 4
- 102000003814 Interleukin-10 Human genes 0.000 claims description 4
- 108090000174 Interleukin-10 Proteins 0.000 claims description 4
- 102000004388 Interleukin-4 Human genes 0.000 claims description 4
- 108090000978 Interleukin-4 Proteins 0.000 claims description 4
- 102000004889 Interleukin-6 Human genes 0.000 claims description 4
- 108090001005 Interleukin-6 Proteins 0.000 claims description 4
- 239000005482 chemotactic factor Substances 0.000 claims description 4
- 229960003130 interferon gamma Drugs 0.000 claims description 4
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 3
- 230000035764 nutrition Effects 0.000 claims description 3
- 235000016709 nutrition Nutrition 0.000 claims description 3
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims description 2
- 102000000018 Chemokine CCL2 Human genes 0.000 claims description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 2
- 102000003812 Interleukin-15 Human genes 0.000 claims description 2
- 108090000172 Interleukin-15 Proteins 0.000 claims description 2
- 108090000171 Interleukin-18 Proteins 0.000 claims description 2
- 102000003810 Interleukin-18 Human genes 0.000 claims description 2
- 102000000588 Interleukin-2 Human genes 0.000 claims description 2
- 108010002350 Interleukin-2 Proteins 0.000 claims description 2
- 102000000704 Interleukin-7 Human genes 0.000 claims description 2
- 108010002586 Interleukin-7 Proteins 0.000 claims description 2
- 102000004890 Interleukin-8 Human genes 0.000 claims description 2
- 108090001007 Interleukin-8 Proteins 0.000 claims description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 2
- 229930003268 Vitamin C Natural products 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 230000006698 induction Effects 0.000 claims description 2
- 229940076144 interleukin-10 Drugs 0.000 claims description 2
- 229940028885 interleukin-4 Drugs 0.000 claims description 2
- 229940100601 interleukin-6 Drugs 0.000 claims description 2
- 229940100994 interleukin-7 Drugs 0.000 claims description 2
- 229940096397 interleukin-8 Drugs 0.000 claims description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 239000011718 vitamin C Substances 0.000 claims description 2
- 235000019154 vitamin C Nutrition 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims 1
- 229960004203 carnitine Drugs 0.000 claims 1
- 235000015097 nutrients Nutrition 0.000 claims 1
- 235000013311 vegetables Nutrition 0.000 claims 1
- 229940046009 vitamin E Drugs 0.000 claims 1
- 241000282472 Canis lupus familiaris Species 0.000 abstract description 33
- 241000282326 Felis catus Species 0.000 abstract description 7
- 208000006820 Arthralgia Diseases 0.000 abstract 1
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 13
- 238000011160 research Methods 0.000 description 7
- 230000008859 change Effects 0.000 description 6
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000005556 hormone Substances 0.000 description 5
- 229940088597 hormone Drugs 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000004068 intracellular signaling Effects 0.000 description 3
- 239000002858 neurotransmitter agent Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 206010060820 Joint injury Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000036995 brain health Effects 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- RZGZRGXCPXHJFW-XVMARJQXSA-N (1s,2s,6s)-2-hydroxy-3-(hydroxymethyl)-7-oxabicyclo[4.1.0]hept-3-en-5-one Chemical compound O[C@H]1C(CO)=CC(=O)[C@H]2O[C@H]21 RZGZRGXCPXHJFW-XVMARJQXSA-N 0.000 description 1
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- 102000007368 Ataxin-7 Human genes 0.000 description 1
- 108010032953 Ataxin-7 Proteins 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 208000018152 Cerebral disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 108010087195 Contactin 1 Proteins 0.000 description 1
- 102100024326 Contactin-1 Human genes 0.000 description 1
- 102100040500 Contactin-6 Human genes 0.000 description 1
- 101710107702 Contactin-6 Proteins 0.000 description 1
- 208000000655 Distemper Diseases 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 102100022197 Glutamate receptor ionotropic, kainate 1 Human genes 0.000 description 1
- 101710112359 Glutamate receptor ionotropic, kainate 1 Proteins 0.000 description 1
- 102100022758 Glutamate receptor ionotropic, kainate 2 Human genes 0.000 description 1
- 101710112360 Glutamate receptor ionotropic, kainate 2 Proteins 0.000 description 1
- 101000577555 Homo sapiens Neuritin Proteins 0.000 description 1
- 101000740126 Homo sapiens Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 102000011830 Neural cell adhesion Human genes 0.000 description 1
- 108050002172 Neural cell adhesion Proteins 0.000 description 1
- 102100028749 Neuritin Human genes 0.000 description 1
- 102100037193 Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 Human genes 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 102000005031 SLC6A15 Human genes 0.000 description 1
- 108060007754 SLC6A15 Proteins 0.000 description 1
- 102000005034 SLC6A16 Human genes 0.000 description 1
- 108060007755 SLC6A16 Proteins 0.000 description 1
- 102000005026 SLC6A18 Human genes 0.000 description 1
- 108060007757 SLC6A18 Proteins 0.000 description 1
- MNCUCCJMXIWMJJ-OWOJBTEDSA-N [(e)-2-thiocyanatoethenyl] thiocyanate Chemical compound N#CS\C=C\SC#N MNCUCCJMXIWMJJ-OWOJBTEDSA-N 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 208000014058 canine distemper Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000005067 joint tissue Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 235000008935 nutritious Nutrition 0.000 description 1
- 150000002898 organic sulfur compounds Chemical class 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical group 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
- A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
- A23K20/147—Polymeric derivatives, e.g. peptides or proteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/174—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Birds (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Fodder In General (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Feed For Specific Animals (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明涉及控制和预防陪伴动物(例如狗或猫)的炎症及减轻陪伴动物(例如狗或猫)的炎性病况，特别是关节炎和关节痛的方法，其包括给予包含硫辛酸的饮食。
Description
本申请为分案申请，原申请的申请日为2011年05月09日，申请号为201180023575.X
(PCT/US2011/035736)，发明名称为“控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法”。
发明领域
本发明涉及控制和预防陪伴动物(例如狗和猫)的炎症以及减轻陪伴动物(例如狗和猫)的炎性病况，特别是关节炎和关节痛的方法，其包括给予包含硫辛酸的饮食(diet)。
发明背景
硫辛酸(LA)为衍生自辛酸的有机硫化合物。LA包含两个通过二硫键连接的邻位硫原子(位于C6和C8)，因此认为其是氧化的(尽管任一硫原子均可存在于更高的氧化态下)。C6位的碳原子是手性的，该分子作为两种对映体R-(+)-硫辛酸(RLA)和S-(-)-硫辛酸(SLA)以及作为外消旋混合物R/S-硫辛酸(R/S-LA)存在。只有R-(+)-对映体天然存在，并且其为四个线粒体酶复合物的必需辅因子。RLA和R/S-LA两者均可作为非处方营养补充剂获得，自20世纪50年代以来已在营养和临床上用于多种疾病和病况。LA已经用于动物食物，例如Hill处方饮食犬b/d® (Hill’s Prescription Diet canine b/d®)，认为其提高警觉性和认知，特别是在年龄较大的狗中。
骨关节炎是由一个或多个关节的软骨、骨和软组织的进行性炎症和退化引起的慢性退行性关节病。类风湿性关节炎为引起炎症和关节损伤的自身免疫病况。二者均为慢性炎性病况，且普遍存在于年龄较大的狗和猫中。由于关节损伤为进行性的且在很大程度上不可逆，主动确定和处理炎性过程是合乎需要的。
发明概述
本发明提供控制和预防陪伴动物(例如狗和猫)的炎症以及减轻陪伴动物(例如狗和猫)的炎性病况，特别是关节炎和关节痛的方法，其包括给予包含硫辛酸的饮食例如至少两周的时间，例如，其中所述饮食包括含有10-10,000
ppm硫辛酸的食物，例如包含50-200 ppm硫辛酸的干燥食物。
在进一步的实施方案中，本发明提供控制和预防陪伴动物(例如狗和猫)的炎症以及减轻陪伴动物(例如狗和猫)的炎性病况，特别是关节炎和关节痛的方法，其包括测量炎症生物标志物的表达，和给予包含硫辛酸的饮食例如至少两周的时间，例如，其中所述饮食包括含有10-10,000
ppm硫辛酸的食物，例如包含50-200 ppm硫辛酸的干燥食物，以减少一个或多个炎症生物标志物的表达。
发明详述
本发明方法使用的饮食包括例如，包含至少500 IU/kg维生素E(例如500-2000 IU/kg)、至少约40 ppm维生素C(例如40-200 ppm)、至少50 ppm肉碱(例如50-300 ppm)和至少50 ppm硫辛酸(例如50-250 ppm)的犬科动物饮食，例如包含以下的犬科动物饮食：
所述硫辛酸为，例如，呈游离或营养上可接受的盐或酯形式，优选游离形式或钠盐形式的R-(+)-硫辛酸(RLA)和S-(-)-硫辛酸(SLA)或外消旋混合物R/S-硫辛酸(R/S-LA)，优选RLA或R/S-LA。
炎症生物标志物包括，例如，下列中的任何一种或多种：肿瘤坏死因子α、GM-集落刺激因子、单核细胞趋化蛋白-1、干扰素γ、白细胞介素-10、白细胞介素-15、白细胞介素-18、白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-7、白细胞介素-8、干扰素γ诱导的蛋白-10、KC趋化因子。
实施例
1
：硫辛酸饮食对老年狗中炎性生物标志物的影响
进行研究以评估食物组合物对健康老年狗中炎性生物标志物和基因表达的影响。本研究包括29只老年比格犬(beagle dog)(初始体重为13.51
± 1.66 kg，年龄10.7 ± 2.33岁)。所有的狗用对照维持食物喂养28天，随后用试验食物喂养。试验食物包含升高水平的Ω3脂肪酸、硫辛酸、来自水果的抗氧化剂和蔬菜混合物、维生素C和E、以及L-肉碱。在控制食物的最后一天(第0天)和试验食物14天后收集血清和全血样品。测量炎性和激素生物标志物以及基因表达变化。根据PAXgene血液RNA试剂盒手册(Qiagen, Valencia, CA)提供的程序提取RNA。将RNA与Affymetrix基因芯片犬-2基因组阵列(Affymetrix GeneChip Canine-2
Genome Array)杂交，并使用稳健多阵列平均(Robust Multi-Array Average)标准化。认为P < 0.05 (在0.1的错误发现率调整值后)且倍数变化范围为至少1.3的转录物具有差异。消耗试验食物后，喂养试验食物的老年狗具有较低的IL-4、IL-6、IL-10、KC和总细胞因子。未检测到激素生物标志物的差异。喂养试验食物的老年狗还具有与第0天相比上调或下调的1123个基因。其中，β淀粉状蛋白斑形成相关基因下调，而β淀粉状蛋白斑清除相关基因上调。此外，当用试验食物喂养老年狗时，与对照的第0天相比，神经递质信号传导和细胞粘附相关基因显著上调。该研究提供基因表达证据，这支持先前所示在老年狗中观察到的试验食物对记忆和行为相关响应的益处。
通过工作和辨别测试(task and discrimination testing)测量，已表明试验食物将老年狗的记忆和认知改善至与年轻狗相似的水平。然而，尚未确定这些所观测到的改善的潜在机制。炎症在许多疾病过程包括一般性老化中起重要作用。此外，认知改善相关的生物化学量度例如基因表达仅在狗中有限使用。
本研究的目的是为了测定试验食物对老年狗中的炎性和激素生物标志物以及基因表达变化的影响。
确定29只阉割/切除卵巢的比格犬用于本研究，用试验食物喂养28天。通过身体检查和血清化学，认为狗是健康的。研究方案由公共机构动物护理和使用委员会(Institutional
Animal Care and Use Committee)审查和批准。所有的狗均针对犬瘟热、腺病毒、细小病毒、博德特氏菌和狂犬病进行免疫，且基于身体检查、全血计数测定、血清生化分析、尿分析和排泄物寄生虫检测的结果无一具有慢性全身性疾病。通过彼此间的互动、与看守人的日常互动和玩耍时间、每日户外奔跑和运动及获得玩具的机会，狗经历行为充实(behavioral enrichment)。在第0天收集样品前，用基础维持对照食物喂养所有的狗达28天。然后将狗的食物改为试验食物，14天后收集样品。抽血并收集入PAXgene管中，-80ºC保存直至进行评估。使用犬-2 Affymetrix基因芯片微列阵确定与第0天相比第14天的基因差异。
血浆生物标志物–采用SAS版本9.0，使用配对t检验分析测定炎性和激素生物标志物响应食物的变化。用所有的细胞因子计算总细胞因子。
基因–使用稳健多阵列平均，将基因表达标准化，并使用Partek分析工具测定差异。认为两组间P < 0.05 (在Q =
0.1的错误发现率调整值后)且倍数变化为至少1.25的基因具有差异。上调基因显示为正的倍数变化。下调基因显示为负的倍数变化。
表
1
：饮食内含物
表
2
：响应于试验食物的血浆中测量的炎性和激素生物标志物
(SE=
平均标准误差
):
表
3
：脑健康和功能相关基因：
| 基因名称 | 倍数变化 |
| 脑健康相关 | |
| 淀粉状蛋白β A4 | -1.3 |
| 共济失调蛋白7 | -1.3 |
| α2巨球蛋白 | 1.3 |
| 脑源性神经营养因子 | 1.3 |
| 其它脑疾病相关 | |
| 蜡样脂褐质沉积症神经元5 | -1.5 |
| 神经细胞粘附相关 | |
| 接触蛋白1 | 1.5 |
| 接触蛋白6 | 1.7 |
| 神经细胞粘附分子 | 1.4 |
| 神经细胞粘附分子2 | 1.5 |
| 神经细胞粘附分子短同工型 | 1.4 |
| 神经递质信号传导和转运蛋白相关 | |
| GABA受体A | 1.3 |
| GABA受体B | 1.3 |
| 谷氨酸受体5 | 1.3 |
| 谷氨酸受体6 | 1.3 |
| 谷氨酸受体8 | 1.3 |
| NMDA 2B | 1.4 |
| Neuritin 1 | 1.3 |
| 乙酰胆碱受体α 6 | 1.3 |
| SLC6A15 | 1.3 |
| SLC6A16 | 1.3 |
| SLC6A18 | 1.3 |
| 钙粘蛋白2 | 1.3 |
| 钠和氯依赖性神经递质转运蛋白NTT5 | 1.3 |
临床研究已表明用试验食物喂养老年狗可帮助恢复青年样能量，并将记忆/工作能力改善至与年轻成年狗相似的水平。在当前研究中，喂养维持对照食物后，将健康老年狗的食物改为试验食物，表现出炎性标志物IL-4、IL-10、IL-6、KC和总细胞因子的降低。另外，β淀粉状蛋白斑形成相关基因降低，而β-淀粉状蛋白清除或神经递质信号传导相关的其它基因增加。
本研究提示，喂养试验食物(通过降低炎性生物标志物和潜在地通过改变脑健康相关基因的表达)对老年狗的生活质量产生正面影响。
Claims (8)
1.包含50-250 ppm硫辛酸、500-2000 IU/kg维生素E、40-200 ppm维生素C、50-300 ppm肉碱和基于干重1-10%的蔬菜混合物的饮食在制备用于控制或预防狗的炎症和/或减轻狗的炎性病况的宠物食物中的用途。
2.权利要求1的用途，其中给予所述宠物食物至少两周的时间。
3.权利要求1或权利要求2的用途，其中待控制、预防或减轻的病况为关节炎。
4.权利要求1或前述权利要求中任一项的用途，其中待治疗、控制、预防或减轻的病况为骨关节炎。
5.权利要求1或前述权利要求中任一项的用途，其中所述硫辛酸为呈游离或营养上可接受的盐或酯形式的R-(+)-硫辛酸(RLA)或外消旋混合物R/S-硫辛酸(R/S-LA)。
6.权利要求1或前述权利要求中任一项的用途，还包括测量炎症生物标志物的表达。
7.权利要求6的用途，其中炎症生物标志物包括选自以下的一种或多种生物标志物：肿瘤坏死因子α、GM-集落刺激因子、单核细胞趋化蛋白-1、干扰素γ、白细胞介素-10、白细胞介素-15、白细胞介素-18、白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-7、白细胞介素-8、干扰素γ诱导的蛋白-10和KC趋化因子。
8.组合物，其以100％干重计包含下列营养物：
。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33403710P | 2010-05-12 | 2010-05-12 | |
| US61/334,037 | 2010-05-12 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201180023575XA Division CN102933092A (zh) | 2010-05-12 | 2011-05-09 | 控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104286456A true CN104286456A (zh) | 2015-01-21 |
Family
ID=44146887
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410479815.2A Pending CN104286456A (zh) | 2010-05-12 | 2011-05-09 | 控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法 |
| CN201180023575XA Pending CN102933092A (zh) | 2010-05-12 | 2011-05-09 | 控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201180023575XA Pending CN102933092A (zh) | 2010-05-12 | 2011-05-09 | 控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20130041020A1 (zh) |
| EP (1) | EP2568824A1 (zh) |
| JP (2) | JP2013532128A (zh) |
| CN (2) | CN104286456A (zh) |
| AU (1) | AU2011253202B2 (zh) |
| BR (1) | BR112012025772A2 (zh) |
| CA (1) | CA2799168C (zh) |
| RU (1) | RU2525579C2 (zh) |
| WO (1) | WO2011143104A1 (zh) |
| ZA (1) | ZA201208036B (zh) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112013028678B1 (pt) * | 2011-05-10 | 2021-07-13 | Société des Produits Nestlé S.A. | Métodos para diagnosticar doença degenerativa das articulações |
| WO2017104277A1 (ja) * | 2015-12-17 | 2017-06-22 | 昭和電工株式会社 | 抗炎症剤及び抗炎症組成物 |
| EP3554256B1 (en) | 2016-12-15 | 2023-07-19 | Société des Produits Nestlé S.A. | Compositions and methods that modulate vitamin d and bone mineral content in a companion animal |
| JP7174151B2 (ja) | 2018-11-02 | 2022-11-17 | ヒルズ・ペット・ニュートリシャン・インコーポレーテッド | ペットフード組成物、炎症状態を治療する方法および循環炎症促進性サイトカインを減少させる方法 |
| CA3164206A1 (en) * | 2019-12-16 | 2021-06-24 | Hill's Pet Nutrition, Inc. | Pet food compositions |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1578627A (zh) * | 2000-10-31 | 2005-02-09 | 高露洁-棕榄公司 | 组合物和方法 |
| EP1635810A2 (en) * | 2003-06-23 | 2006-03-22 | Advanced Bionutrition (Europe) Limited | Inflammatory disease treatment |
| CN1809344A (zh) * | 2001-10-03 | 2006-07-26 | 艾蒂尔药物有限公司 | 抗氧化组合物及其用途 |
| CN101098623A (zh) * | 2004-11-09 | 2008-01-02 | 希尔氏宠物营养品公司 | 抗氧化剂用于基因调节的用途 |
| US20090182032A1 (en) * | 2000-10-31 | 2009-07-16 | Hill's Pet Nutrition, Inc. | Companion animal compositions including lipoic acid and methods of use thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5569670A (en) | 1992-06-05 | 1996-10-29 | Asta Medica Aktiengesellschaft | Combination medications containing alpha-lipoic acid and related |
| ATE290400T1 (de) | 2000-01-20 | 2005-03-15 | Innovet Italia Srl | Zusammensetzung zur behandlung von degenerativen gelenkerkrankungen |
| CA2571742C (en) * | 2004-07-01 | 2013-01-15 | Nestec S.A. | Canine osteoarthritis diet formulation |
| JP5138380B2 (ja) * | 2004-11-24 | 2013-02-06 | ヒルズ・ペット・ニュートリシャン・インコーポレーテッド | 動物における免疫応答を増大させる方法 |
| EP1830629A4 (en) * | 2004-12-30 | 2008-08-27 | Hills Pet Nutrition Inc | METHODS FOR ENHANCING THE QUALITY OF LIFE OF AN ANIMAL AGE |
| EP2320752A1 (en) * | 2008-07-18 | 2011-05-18 | Hill's Pet Nutrition, Inc. | Method for enhancing the quality of life of a senior animal |
| BRPI0915986A2 (pt) * | 2008-07-18 | 2015-11-03 | Hills Pet Nutrition Inc | composição, métodos para tratar uma condição, para retardar o início de uma condição, para reduzir o risco em um indivíduo de adquirir uma condição e para alterar a expressão de um ou mais genes em um indivíduo |
| WO2010078322A1 (en) * | 2008-12-30 | 2010-07-08 | Hill's Pet Nutrition, Inc. | Use of lipoic acid for treating or preventing degenerative joint conditions, osteoarthritis, cartilage damage, and related disorders in companion animals |
-
2011
- 2011-05-09 AU AU2011253202A patent/AU2011253202B2/en active Active
- 2011-05-09 WO PCT/US2011/035736 patent/WO2011143104A1/en not_active Ceased
- 2011-05-09 CN CN201410479815.2A patent/CN104286456A/zh active Pending
- 2011-05-09 BR BR112012025772A patent/BR112012025772A2/pt not_active Application Discontinuation
- 2011-05-09 CA CA2799168A patent/CA2799168C/en active Active
- 2011-05-09 US US13/642,561 patent/US20130041020A1/en not_active Abandoned
- 2011-05-09 JP JP2013510203A patent/JP2013532128A/ja active Pending
- 2011-05-09 RU RU2012153558/13A patent/RU2525579C2/ru not_active IP Right Cessation
- 2011-05-09 CN CN201180023575XA patent/CN102933092A/zh active Pending
- 2011-05-09 EP EP11720683A patent/EP2568824A1/en not_active Ceased
-
2012
- 2012-10-24 ZA ZA2012/08036A patent/ZA201208036B/en unknown
-
2014
- 2014-12-05 JP JP2014246783A patent/JP6334379B2/ja active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1578627A (zh) * | 2000-10-31 | 2005-02-09 | 高露洁-棕榄公司 | 组合物和方法 |
| US20090182032A1 (en) * | 2000-10-31 | 2009-07-16 | Hill's Pet Nutrition, Inc. | Companion animal compositions including lipoic acid and methods of use thereof |
| CN1809344A (zh) * | 2001-10-03 | 2006-07-26 | 艾蒂尔药物有限公司 | 抗氧化组合物及其用途 |
| EP1635810A2 (en) * | 2003-06-23 | 2006-03-22 | Advanced Bionutrition (Europe) Limited | Inflammatory disease treatment |
| CN101098623A (zh) * | 2004-11-09 | 2008-01-02 | 希尔氏宠物营养品公司 | 抗氧化剂用于基因调节的用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102933092A (zh) | 2013-02-13 |
| AU2011253202B2 (en) | 2014-04-24 |
| RU2525579C2 (ru) | 2014-08-20 |
| CA2799168A1 (en) | 2011-11-17 |
| BR112012025772A2 (pt) | 2015-09-22 |
| JP2015071633A (ja) | 2015-04-16 |
| CA2799168C (en) | 2015-07-07 |
| JP2013532128A (ja) | 2013-08-15 |
| RU2012153558A (ru) | 2014-06-20 |
| JP6334379B2 (ja) | 2018-05-30 |
| US20130041020A1 (en) | 2013-02-14 |
| EP2568824A1 (en) | 2013-03-20 |
| ZA201208036B (en) | 2017-08-30 |
| WO2011143104A1 (en) | 2011-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tan et al. | Molecular genetic studies of gene identification for sarcopenia | |
| EP2315532B1 (en) | Compositions and methods for treating disorders associated with overweight animals | |
| RU2619553C2 (ru) | Композиции и способы для лечения остеоартрита | |
| CN104286456A (zh) | 控制和预防陪伴动物炎症及减轻陪伴动物炎性病况的方法 | |
| EP3547845B1 (en) | Pet food compositions | |
| CA2731088C (en) | Methods for enhancing the quality of life of a senior animal | |
| CN102884434B (zh) | 用于诊断、控制和预防犬科动物炎症及减轻犬科动物炎性病况的方法 | |
| Ranard et al. | Synthetic α-tocopherol, compared with natural α-tocopherol, downregulates myelin genes in cerebella of adolescent Ttpa-null mice | |
| AU2011253202A1 (en) | Methods of control and prophylaxis of inflammation and mitigation of inflammatory conditions in companion animals | |
| Shcherbitskaya et al. | The effects of prenatal hyperhomocysteinemia on the formation of memory and the contents of biogenic amines in the rat hippocampus | |
| EP3899045B1 (en) | Methods for identifying a companion animal susceptible to treatment that reduces the risk of stone formation and use of compositions for reducing such risk | |
| Brown Jr et al. | Effects of heat shock protein-70 gene and forage system on milk yield and composition of beef cattle | |
| KR102600368B1 (ko) | 이노토디올을 포함하는 근육 질환의 예방 또는 치료용 조성물 | |
| Dang et al. | Ultra-early weaning alters growth performance, hematology parameters, and fecal microbiota in piglets with same genetic background | |
| Claude et al. | Feeding Strategies for Slow-Growing Broilers in the Tropics: Production Efficiency and Welfare Behavior | |
| Hammers et al. | Piglet birth weight but not the timing of zinc supplementation in gestation diets affects tissue mineral concentrations and gene expression | |
| WO2024259200A1 (en) | Bacterial associations with gingivitis and periodontitis in animal, for example yorkshire terriers | |
| Žymantienė et al. | Assessment of gut microbiota and serum biochemistry parameters in rats fed commercial pellet diet containing different protein content. | |
| Gohel et al. | Chi-Fai Ng (2018): Cytokine and inflammatory-related gene expression of melamine cyanurate on human renal proximal tubular cells | |
| Gotoh | Metabolic imprinting effect in beef production: Effects of nutritional manipulation during an early stage on the beef quality and quantity in wagyu (Japanese Black) and holstein cattle | |
| Martínez-Aranzales et al. | Fecal Microbiome of Horses with and Without Crib-Biting Behavior: A Comparative Study | |
| CN102883624A (zh) | 诊断、控制和预防猫科动物炎症和缓解炎性病况的方法 | |
| CA2862200A1 (en) | Methods for enhancing the quality of life of a senior animal |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150121 |