CA2526899A1 - Method for the treatment of diseases linked to an accumulation of triglycerides and cholesterol - Google Patents
Method for the treatment of diseases linked to an accumulation of triglycerides and cholesterol Download PDFInfo
- Publication number
- CA2526899A1 CA2526899A1 CA002526899A CA2526899A CA2526899A1 CA 2526899 A1 CA2526899 A1 CA 2526899A1 CA 002526899 A CA002526899 A CA 002526899A CA 2526899 A CA2526899 A CA 2526899A CA 2526899 A1 CA2526899 A1 CA 2526899A1
- Authority
- CA
- Canada
- Prior art keywords
- mice
- aminoisobutyric acid
- treatment
- beta
- cholesterol
- 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.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 85
- 150000003626 triacylglycerols Chemical class 0.000 title claims abstract description 67
- 238000000034 method Methods 0.000 title claims abstract description 52
- 238000009825 accumulation Methods 0.000 title claims abstract description 17
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 title claims description 114
- 235000012000 cholesterol Nutrition 0.000 title claims description 51
- 201000010099 disease Diseases 0.000 title description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 11
- JHTPBGFVWWSHDL-UHFFFAOYSA-N 1,4-dichloro-2-isothiocyanatobenzene Chemical compound ClC1=CC=C(Cl)C(N=C=S)=C1 JHTPBGFVWWSHDL-UHFFFAOYSA-N 0.000 claims abstract description 91
- 239000002207 metabolite Substances 0.000 claims abstract description 35
- 239000000651 prodrug Substances 0.000 claims abstract description 35
- 229940002612 prodrug Drugs 0.000 claims abstract description 35
- 239000013543 active substance Substances 0.000 claims abstract description 32
- 210000004369 blood Anatomy 0.000 claims abstract description 32
- 239000008280 blood Substances 0.000 claims abstract description 32
- 230000006806 disease prevention Effects 0.000 claims abstract description 13
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 66
- 210000000577 adipose tissue Anatomy 0.000 claims description 59
- 241001465754 Metazoa Species 0.000 claims description 54
- 210000004185 liver Anatomy 0.000 claims description 51
- 102000004877 Insulin Human genes 0.000 claims description 33
- 108090001061 Insulin Proteins 0.000 claims description 33
- 229940125396 insulin Drugs 0.000 claims description 33
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 33
- 108010023302 HDL Cholesterol Proteins 0.000 claims description 31
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- QCHPKSFMDHPSNR-UHFFFAOYSA-N 3-aminoisobutyric acid Chemical compound NCC(C)C(O)=O QCHPKSFMDHPSNR-UHFFFAOYSA-N 0.000 claims description 19
- 230000002265 prevention Effects 0.000 claims description 19
- 210000001519 tissue Anatomy 0.000 claims description 19
- 102000011690 Adiponectin Human genes 0.000 claims description 18
- 108010076365 Adiponectin Proteins 0.000 claims description 18
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 18
- 239000008103 glucose Substances 0.000 claims description 18
- 231100000240 steatosis hepatitis Toxicity 0.000 claims description 17
- 230000036765 blood level Effects 0.000 claims description 16
- 230000007423 decrease Effects 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- 235000016709 nutrition Nutrition 0.000 claims description 15
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 14
- 208000004930 Fatty Liver Diseases 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 206010020772 Hypertension Diseases 0.000 claims description 12
- 230000009467 reduction Effects 0.000 claims description 11
- 201000005577 familial hyperlipidemia Diseases 0.000 claims description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 6
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 208000010706 fatty liver disease Diseases 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 230000035945 sensitivity Effects 0.000 claims description 5
- 206010002383 Angina Pectoris Diseases 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 3
- 238000010171 animal model Methods 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 208000019423 liver disease Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229910017053 inorganic salt Inorganic materials 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 230
- 238000002474 experimental method Methods 0.000 description 51
- 150000002632 lipids Chemical class 0.000 description 50
- 235000021068 Western diet Nutrition 0.000 description 41
- 235000000891 standard diet Nutrition 0.000 description 36
- 238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 35
- 230000000694 effects Effects 0.000 description 21
- 208000008589 Obesity Diseases 0.000 description 20
- 230000003247 decreasing effect Effects 0.000 description 19
- 235000020824 obesity Nutrition 0.000 description 19
- 239000003651 drinking water Substances 0.000 description 18
- 235000020188 drinking water Nutrition 0.000 description 18
- 238000005259 measurement Methods 0.000 description 18
- 230000009286 beneficial effect Effects 0.000 description 15
- 238000011835 investigation Methods 0.000 description 14
- 206010022489 Insulin Resistance Diseases 0.000 description 13
- 206010016654 Fibrosis Diseases 0.000 description 12
- 230000035508 accumulation Effects 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 230000007863 steatosis Effects 0.000 description 12
- 102000016267 Leptin Human genes 0.000 description 11
- 108010092277 Leptin Proteins 0.000 description 11
- 235000021588 free fatty acids Nutrition 0.000 description 11
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 11
- 229940039781 leptin Drugs 0.000 description 11
- 150000003904 phospholipids Chemical class 0.000 description 11
- 230000037396 body weight Effects 0.000 description 10
- 230000004761 fibrosis Effects 0.000 description 10
- 230000002440 hepatic effect Effects 0.000 description 10
- 235000005911 diet Nutrition 0.000 description 9
- 230000037213 diet Effects 0.000 description 9
- 150000005830 nonesterified fatty acids Chemical class 0.000 description 9
- 108010010234 HDL Lipoproteins Proteins 0.000 description 8
- 102000015779 HDL Lipoproteins Human genes 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 8
- 108010007622 LDL Lipoproteins Proteins 0.000 description 8
- 102000007330 LDL Lipoproteins Human genes 0.000 description 8
- 206010028851 Necrosis Diseases 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 230000017074 necrotic cell death Effects 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 230000036470 plasma concentration Effects 0.000 description 7
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 6
- 108010082126 Alanine transaminase Proteins 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 208000006575 hypertriglyceridemia Diseases 0.000 description 4
- 238000013116 obese mouse model Methods 0.000 description 4
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 108010028554 LDL Cholesterol Proteins 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 238000001949 anaesthesia Methods 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 235000021233 hypercaloric diet Nutrition 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 1
- MZFOKIKEPGUZEN-AGCMQPJKSA-N (R)-methylmalonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)[C@@H](C(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MZFOKIKEPGUZEN-AGCMQPJKSA-N 0.000 description 1
- ZHTJVFJXNTXXOV-UHFFFAOYSA-N 1-(5-acetyl-2,6-dimethyl-1,2-dihydropyridin-3-yl)ethanone Chemical compound CC1NC(C)=C(C(C)=O)C=C1C(C)=O ZHTJVFJXNTXXOV-UHFFFAOYSA-N 0.000 description 1
- VOKUMXABRRXHAR-UHFFFAOYSA-N 2-methyl-3-oxopropanoic acid Chemical compound O=CC(C)C(O)=O VOKUMXABRRXHAR-UHFFFAOYSA-N 0.000 description 1
- 208000004611 Abdominal Obesity Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102000014777 Adipokines Human genes 0.000 description 1
- 108010078606 Adipokines Proteins 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000237519 Bivalvia Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010065941 Central obesity Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010014486 Elevated triglycerides Diseases 0.000 description 1
- 241000009120 Elymus fibrosus Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000276438 Gadus morhua Species 0.000 description 1
- 241000272496 Galliformes Species 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 206010061998 Hepatic lesion Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 206010028604 Myocardial rupture Diseases 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 241000237502 Ostreidae Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 241000276707 Tilapia Species 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 239000000478 adipokine Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940024545 aluminum hydroxide Drugs 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000020639 clam Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 208000012696 congenital leptin deficiency Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 238000000892 gravimetry Methods 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 210000001596 intra-abdominal fat Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 230000004322 lipid homeostasis Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 208000001022 morbid obesity Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000020636 oyster Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- QAQREVBBADEHPA-IEXPHMLFSA-N propionyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QAQREVBBADEHPA-IEXPHMLFSA-N 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004141 reverse cholesterol transport Effects 0.000 description 1
- 239000004248 saffron Substances 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- VNOYUJKHFWYWIR-ITIYDSSPSA-N succinyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 VNOYUJKHFWYWIR-ITIYDSSPSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 208000019553 vascular disease Diseases 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
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- 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
-
- 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
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- 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)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Food Science & Technology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IBPCT/IB03/01463 | 2003-04-18 | ||
| PCT/IB2003/001463 WO2004091598A1 (en) | 2003-04-18 | 2003-04-18 | Use of beta-aminoisobutyric acid for the treatment of diseases linked to the accumulation of triglycerides and cholesterol |
| PCT/IB2004/001166 WO2004091599A1 (en) | 2003-04-18 | 2004-04-15 | Method for the treatment of diseases linked to an accumulation of triglycerides and cholesterol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2526899A1 true CA2526899A1 (en) | 2004-10-28 |
Family
ID=33187198
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002526899A Abandoned CA2526899A1 (en) | 2003-04-18 | 2004-04-15 | Method for the treatment of diseases linked to an accumulation of triglycerides and cholesterol |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20060167098A1 (enExample) |
| EP (1) | EP1615630A1 (enExample) |
| JP (1) | JP2006523672A (enExample) |
| AU (1) | AU2003226582A1 (enExample) |
| BR (1) | BRPI0409456A (enExample) |
| CA (1) | CA2526899A1 (enExample) |
| WO (2) | WO2004091598A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8367072B2 (en) * | 2006-12-08 | 2013-02-05 | Polifenoles Naturales, S.L. | Composition for treating obesity and method of using the same |
| WO2012066549A1 (en) * | 2010-11-15 | 2012-05-24 | Ramot At Tel-Aviv University Ltd. | Dipeptide analogs for treating conditions associated with amyloid fibril formation |
| CN105250256A (zh) * | 2015-10-16 | 2016-01-20 | 南京医科大学 | β-氨基异丁酸在制备抗糖尿病药物中的应用 |
| JP2019510041A (ja) * | 2016-03-30 | 2019-04-11 | マイクロバイオ カンパニー， リミテッド | 免疫チェックポイントモジュレーターおよび共生微生物叢による発酵産物の併用がん療法 |
| JP2019131488A (ja) * | 2018-01-29 | 2019-08-08 | 静岡県公立大学法人 | Ｖｃａｍ−１発現抑制剤、ｍｃｐ−１発現抑制剤、炎症性疾患改善用組成物、加工食品又は飲料 |
| US20220347141A1 (en) * | 2019-09-17 | 2022-11-03 | Yale University | Methods of treating phosphate concentration disorders with l-baiba |
| AU2022258161B2 (en) * | 2021-04-14 | 2025-05-22 | Nanjing Nutrabuilding Bio-Tech Co., Ltd. | Compositions and methods for promoting glycogen synthase activity and augmenting glycogen storage capability |
| CN117561056A (zh) * | 2021-06-22 | 2024-02-13 | 南京纽邦生物科技有限公司 | 施用β-氨基异丁酸增加间歇性禁食减肥的益处 |
| CN115606809A (zh) * | 2021-10-08 | 2023-01-17 | 南京纽邦生物科技有限公司 | 通过施用β-氨基异丁酸模拟热量限制的生物学益处的方法和组合物 |
| CN116059195A (zh) * | 2022-01-28 | 2023-05-05 | 南京纽邦生物科技有限公司 | 用于提高运动表现或预防或缓解疲劳的组合物和方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4453941A (en) * | 1980-12-29 | 1984-06-12 | Board Of Overseers Of Goshen College | Composition and process for producing pigmentation in hair or skin |
| DE4115468A1 (de) * | 1991-05-11 | 1992-11-12 | Behringwerke Ag | Amidinophenylalaninderivate, verfahren zu deren herstellung, deren verwendung und diese enthaltende mittel als antikoagulantien |
| FR2701948B1 (fr) * | 1993-02-22 | 1996-07-26 | Exsymol Sa | Produit de couplage de l'histamine ou l'histamine méthyl-substituée et d'un acide aminé, procédé de préparation et applications thérapeutiques, cosmétologiques et agroalimentaires. |
| JPH07101984A (ja) * | 1993-09-30 | 1995-04-18 | Suntory Ltd | ペプチド誘導体 |
| JPH107553A (ja) * | 1996-03-21 | 1998-01-13 | Toutoushiyu Seizo Kk | 生体内ラジカル消去剤及び抗潰瘍剤 |
-
2003
- 2003-04-18 AU AU2003226582A patent/AU2003226582A1/en not_active Abandoned
- 2003-04-18 WO PCT/IB2003/001463 patent/WO2004091598A1/en not_active Ceased
-
2004
- 2004-04-15 EP EP04727612A patent/EP1615630A1/en not_active Withdrawn
- 2004-04-15 US US10/553,807 patent/US20060167098A1/en not_active Abandoned
- 2004-04-15 JP JP2006506481A patent/JP2006523672A/ja not_active Withdrawn
- 2004-04-15 WO PCT/IB2004/001166 patent/WO2004091599A1/en not_active Ceased
- 2004-04-15 BR BRPI0409456-5A patent/BRPI0409456A/pt not_active Application Discontinuation
- 2004-04-15 CA CA002526899A patent/CA2526899A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2006523672A (ja) | 2006-10-19 |
| US20060167098A1 (en) | 2006-07-27 |
| WO2004091598A1 (en) | 2004-10-28 |
| AU2003226582A1 (en) | 2004-11-04 |
| EP1615630A1 (en) | 2006-01-18 |
| WO2004091599A1 (en) | 2004-10-28 |
| BRPI0409456A (pt) | 2006-04-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2331408C (en) | Fatty analogues for the treatment of obesity, hypertension and fatty liver | |
| CA2784836A1 (en) | Improved method of administering .beta.-hydroxy-.beta.-methylbutyrate (hmb) | |
| WO1993003714A2 (en) | Method for treatment of metabolic disorders | |
| US20060167098A1 (en) | Method for the treatment of diseases linked to an accumulation of triglycerides and cholesterol | |
| RU2375055C2 (ru) | Применение альфа-кетоглутарата и родственных соединений для снижения липидов плазмы | |
| JP3858055B2 (ja) | 抗肥満剤及び脂質代謝改善剤 | |
| CN120583948A (zh) | 施用dhb增加间歇禁食的减重益处 | |
| US7388030B2 (en) | Suppressors of anemia and appetite suppressors and methods for suppressing anemia and suppressing appetite | |
| JP2007262017A (ja) | ピペコリン酸含有抗糖尿病組成物 | |
| JP3915999B2 (ja) | 抗肥満剤及び脂質代謝改善剤 | |
| WO2001028365A1 (en) | Dietary supplement | |
| AU2022332335A1 (en) | Compositions and methods for preventing or reducing the risk of metabolic syndrome | |
| HK1107018B (en) | Use of alpha-ketoglutarate and related compounds for lowering plasma lipids | |
| JPWO2001091762A1 (ja) | 経口投与による亜鉛補給組成物 | |
| HK1053265A (en) | Novel fatty acid analogues for the treatment of hypertension | |
| MXPA06002948A (en) | Enhanced method of treatment of growth disorders | |
| HK1051967A (en) | Novel fatty acid analogues for the treatment of fatty liver | |
| HK1116999A (en) | A method and composition for nutritionally improving glucose control and insulin action | |
| HK1034912B (en) | Novel fatty analogues for the treatment of obesity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |