JP2022545299A - β-ヒドロキシ-β-メチルブチレート(HMB)中のビタミンDの安定性 - Google Patents
β-ヒドロキシ-β-メチルブチレート(HMB)中のビタミンDの安定性 Download PDFInfo
- Publication number
- JP2022545299A JP2022545299A JP2020572417A JP2020572417A JP2022545299A JP 2022545299 A JP2022545299 A JP 2022545299A JP 2020572417 A JP2020572417 A JP 2020572417A JP 2020572417 A JP2020572417 A JP 2020572417A JP 2022545299 A JP2022545299 A JP 2022545299A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- hmb
- formulation
- hmbfa
- acid
- 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
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 title claims abstract description 80
- 229930003316 Vitamin D Natural products 0.000 title claims abstract description 57
- 235000019166 vitamin D Nutrition 0.000 title claims abstract description 57
- 239000011710 vitamin D Substances 0.000 title claims abstract description 57
- 150000003710 vitamin D derivatives Chemical class 0.000 title claims abstract description 57
- 229940046008 vitamin d Drugs 0.000 title claims abstract description 57
- AXFYFNCPONWUHW-UHFFFAOYSA-N 3-hydroxyisovaleric acid Chemical compound CC(C)(O)CC(O)=O AXFYFNCPONWUHW-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 74
- 238000009472 formulation Methods 0.000 claims abstract description 40
- 230000000087 stabilizing effect Effects 0.000 claims abstract description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 12
- 230000002378 acidificating effect Effects 0.000 claims abstract description 9
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 21
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 20
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 20
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 20
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 18
- 235000013305 food Nutrition 0.000 claims description 14
- 229960004203 carnitine Drugs 0.000 claims description 6
- QRYRORQUOLYVBU-VBKZILBWSA-N carnosic acid Chemical compound CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 claims description 6
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 6
- 229940092258 rosemary extract Drugs 0.000 claims description 6
- 235000020748 rosemary extract Nutrition 0.000 claims description 6
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 claims description 6
- 235000010199 sorbic acid Nutrition 0.000 claims description 6
- 229940075582 sorbic acid Drugs 0.000 claims description 6
- 239000004334 sorbic acid Substances 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 5
- 230000015556 catabolic process Effects 0.000 claims description 4
- 238000006731 degradation reaction Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 claims 3
- -1 softgels Substances 0.000 claims 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 31
- 239000011647 vitamin D3 Substances 0.000 description 27
- 229940021056 vitamin d3 Drugs 0.000 description 24
- 235000005282 vitamin D3 Nutrition 0.000 description 23
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 8
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 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 description 6
- 235000015872 dietary supplement Nutrition 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000002738 chelating agent Substances 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 239000002417 nutraceutical Substances 0.000 description 4
- 235000021436 nutraceutical agent Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 3
- QUKRTJQSGPLQKQ-UHFFFAOYSA-N 5-methylsulfonyl-3h-1,3-benzoxazol-2-one Chemical compound CS(=O)(=O)C1=CC=C2OC(=O)NC2=C1 QUKRTJQSGPLQKQ-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 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 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 230000009469 supplementation Effects 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 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 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004420 Creatine Kinase Human genes 0.000 description 2
- 108010042126 Creatine kinase Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- WHIQZYTVWTZJNO-GMPZOFGBSA-N (1s)-3-[(e)-2-[(1r,7ar)-1-[(e,2r,5r)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-1,2,3,5,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-3-en-1-ol Chemical compound C([C@@H]([C@]1(CCC2)C)[C@H](C)/C=C/[C@H](C)C(C)C)CC1=C2\C=C\C1=C(C)CC[C@H](O)C1 WHIQZYTVWTZJNO-GMPZOFGBSA-N 0.000 description 1
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-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[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- UCTLRSWJYQTBFZ-UHFFFAOYSA-N Dehydrocholesterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCCC(C)C)CCC33)C)C3=CC=C21 UCTLRSWJYQTBFZ-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241001529742 Rosmarinus Species 0.000 description 1
- 244000178231 Rosmarinus officinalis Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000037118 bone strength Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 239000000470 constituent Substances 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
- 229960002433 cysteine Drugs 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002270 ergogenic effect Effects 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 235000020988 fatty fish Nutrition 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 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 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000019692 hotdogs Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 150000002614 leucines Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 150000003338 secosteroids Chemical group 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000036561 sun exposure Effects 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000020799 vitamin D status Nutrition 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- A23L33/15—Vitamins
- A23L33/155—Vitamins A or D
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
1. 分野
本発明は、β-ヒドロキシ-β-メチルブチレート(HMB)およびビタミンDを含む組成物に関する。特に、本発明は、HMBおよびビタミンDを含有する組成物、ならびにビタミンDを酸性組成物と組み合わせた際に、ビタミンDを安定化させる方法に関する。
ビタミンDは、古典的に、カルシウムおよびリン代謝、ならびに骨強度と関連付けられてきている。最近まで、ビタミンD欠乏疾患であるクル病を用いて、適切なビタミンDレベルが定義されてきた。近年、ビタミンDは、カルシウムおよび骨構造以外の代謝に、より広い影響を有することが見出されてきている。低ビタミンD状態は、以下:骨粗鬆症、転倒(falls)、I型糖尿病、癌、自己免疫疾患、高血圧、歯周病、多発性硬化症、感染に対する感受性/劣った反応に関連付けられてきている1。
アルファ-ケトイソカプロン酸(KIC)は、ロイシンの最初の主な、そして活性である代謝産物である。KIC代謝の少量の産物は、β-ヒドロキシ-β-メチルブチレート(HMB)である。HMBは、多様な適用の背景内で有用であることが見出されてきている。特に、米国特許第5,360,613号(Nissen)において、HMBは総コレステロールおよび低密度リポタンパク質コレステロールの血中レベルを減少させるために有用であると記載される。米国特許第5,348,979号(Nissenら)において、HMBはヒトにおいて窒素保持を促進するために有用であると記載される。米国特許第5,028,440号(Nissen)は、動物における除脂肪組織発展を増加させるためのHMBの有用性を論じる。また、米国特許第4,992,470号(Nissen)には、HMBは哺乳動物の免疫反応を増進させる際に有効であると記載される。米国特許第6,031,000号(Nissenら)は、疾患関連消耗を治療するためのHMBおよび少なくとも1つのアミノ酸の使用を記載する。
本発明の1つの目的は、HMBFAおよび安定であるビタミンDを含有する組成物を提供することである。
本発明のこれらのおよび他の目的は、以下の明細書、図、および請求項を参照すると、当業者には明らかとなるであろう。
本発明に含まれる安定化賦形剤には、EDTA、あるいはBHT、BHA、パルミチン酸アスコルビル、没食子酸プロピル、ビタミンE、アスコルビン酸、システイン、メチオニン、モノチオグリセロール、チオ硫酸ナトリウム、または亜硫酸塩を含む、酸化防止剤が含まれる。
本発明の背景内で、任意の適切な用量のHMBを用いてもよい。適切な用量を計算する方法が、当該技術分野に周知である。
用語、投与することまたは投与には、組成物およびその組み合わせを消費する哺乳動物に組成物を提供する工程が含まれる。
方法:11の異なるHMBFA/ビタミンD3配合物を試験した。これらの配合物を、経時的なビタミンD3の安定性に関して試験した。配合物は以下の通りであった:
1. HMBFA+ビタミンD3(100HP、BASF、デンマーク)
2. 塩化コリン(Acros Organics)を加えたHMB FA中のビタミンD3(100HP、BASF、デンマーク)
3. ベタイン(Sigma-Aldrich)を加えたHMB FA中のビタミンD3(100HP、BASF、デンマーク)
4. 緩衝HMBFA+ビタミンD3(100HP、BASF、デンマーク)
5. 緩衝HMBFA+BASF保護ビタミンD3(100GFP/HP、BASF、デンマーク)
6. HMBFA+NovaSol D(登録商標)保護ビタミンD3(AquaNova(登録商標)、ドイツ)
7. 60ppm EDTA二ナトリウム(VerseneTM NAキレート剤、Dow Chemical、ミシガン州ミッドランド)で安定化された、緩衝HMB遊離酸+NovaSol D(登録商標)保護ビタミンD3(AquaNova、ドイツ)
8. 60ppm EDTA二ナトリウム(VerseneTM NAキレート剤、Dow Chemical、ミシガン州ミッドランド)で安定化された、HMBFA+NovaSol D(登録商標)保護ビタミンD3(AquaNova、ドイツ)
9. 60ppm EDTA二ナトリウム(VerseneTM NAキレート剤、Dow Chemical、ミシガン州ミッドランド)で安定化された、緩衝HMBFA+ビタミンD3(Sigma-Aldrich)
10. BHT(ブチル化ヒドロキシトルエン、Sigma-Aldrich)で安定化された、緩衝HMBFA+NovaSol D(登録商標)ビタミンD3(AquaNova、ドイツ)+L-カルニチン
11. NovaSolローズマリー(登録商標)、NovaSol DS/4(登録商標)、およびBHT(ブチル化ヒドロキシトルエン、Sigma-Aldrich)で安定化された、緩衝HMBFA+NovaSol D(登録商標)ビタミンD3(AquaNova、ドイツ)+L-カルニチン
ビタミンD3を、HeartlandアッセイによりHPLCによって測定した。
簡潔には、400g HMBFA(TSIロット12111036)を1リットルビーカー内に測り入れ、そして次いで、37.8gの炭酸カリウム(K2CO3)をHMBFAに添加した。攪拌バーを加え、そして混合物を60時間攪拌した。生じたpHはおよそ4.5であった。あるいは、水(35g)を炭酸カリウム(37g)と混合し、そして次いで、HMBFA(400g)を添加することによって、反応を加速してもよい。
Claims (10)
- 遊離酸型のβ-ヒドロキシ-β-メチルブチレート(HMB)、ビタミンDおよび少なくとも1つの安定化賦形剤を含む、安定配合物。
- 安定化賦形剤が、EDTA、ブチル化ヒドロキシトルエン(BHT)、カルニチン、ローズマリー抽出物、カルノソル酸、およびソルビン酸からなるリストより選択される、請求項1の配合物。
- 安定化賦形剤が、EDTAおよびブチル化ヒドロキシトルエン(BHT)からなるリストより選択される、請求項1の配合物。
- 配合物が、カプセル、ソフトゲル、液体、および食品からなるリストより選択される送達型内に含有される、請求項1の配合物。
- ビタミンDおよびβ-ヒドロキシ-β-メチルブチレート(HMB)を含有する配合物中に、少なくとも1つの安定化賦形剤を含める工程を含む、酸性組成物中のビタミンDを安定化させる方法。
- HMBが遊離酸型である、請求項5の方法。
- 安定化賦形剤が、EDTA、ブチル化ヒドロキシトルエン(BHT)、カルニチン、ローズマリー抽出物、カルノソル酸、およびソルビン酸からなるリストより選択される、請求項5の方法。
- β-ヒドロキシ-β-メチルブチレート(HMB)およびビタミンDを含有する酸性配合物中のビタミンDの分解を最小限にする方法であって、前記配合物中に少なくとも1つの安定化賦形剤を含める工程を含む、前記方法。
- HMBが遊離酸型である、請求項8の方法。
- 安定化賦形剤が、EDTA、ブチル化ヒドロキシトルエン(BHT)、カルニチン、ローズマリー抽出物、カルノソル酸、およびソルビン酸からなるリストより選択される、請求項8の方法。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/US2019/038948 WO2020263229A1 (en) | 2019-06-25 | 2019-06-25 | STABILITY OF VITAMIN D IN β-HYDROXY- β-METHYLBUTYRATE (HMB) |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2022545299A true JP2022545299A (ja) | 2022-10-27 |
Family
ID=74060572
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020572417A Pending JP2022545299A (ja) | 2019-06-25 | 2019-06-25 | β-ヒドロキシ-β-メチルブチレート(HMB)中のビタミンDの安定性 |
Country Status (7)
Country | Link |
---|---|
JP (1) | JP2022545299A (ja) |
KR (1) | KR20220050082A (ja) |
CN (1) | CN113056206A (ja) |
AU (1) | AU2019453386A1 (ja) |
CA (1) | CA3105039A1 (ja) |
SG (1) | SG11202012984YA (ja) |
WO (1) | WO2020263229A1 (ja) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060019933A1 (en) * | 2004-07-22 | 2006-01-26 | David Boardman | Process for preparing stabilized vitamin D |
JP2014509842A (ja) * | 2011-02-07 | 2014-04-24 | アボット・ラボラトリーズ | β−ヒドロキシ−β−メチルブチラートを含む栄養製品 |
JP2017510629A (ja) * | 2014-03-14 | 2017-04-13 | メタボリック・テクノロジーズ,インコーポレーテッド | 遊離酸形のβ−ヒドロキシ−β−メチル酪酸(HMB)を含有する液体及び食品ならびにその製造法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6849613B2 (en) * | 2001-08-29 | 2005-02-01 | Kedar N. Prasad | Multiple antioxidant micronutrients |
US20100178369A1 (en) * | 2009-01-15 | 2010-07-15 | Nicole Lee Arledge | Antioxidant-stabilized concentrated fish oil |
CN102512655B (zh) * | 2011-11-30 | 2013-10-30 | 北京康比特体育科技股份有限公司 | 左旋肉碱组合物和制剂,及其制备方法和应用 |
CN109862875A (zh) * | 2016-03-30 | 2019-06-07 | 西姆莱斯股份公司 | 一种活性混合物 |
-
2019
- 2019-06-25 WO PCT/US2019/038948 patent/WO2020263229A1/en unknown
- 2019-06-25 CN CN201980057166.8A patent/CN113056206A/zh active Pending
- 2019-06-25 AU AU2019453386A patent/AU2019453386A1/en active Pending
- 2019-06-25 CA CA3105039A patent/CA3105039A1/en active Pending
- 2019-06-25 SG SG11202012984YA patent/SG11202012984YA/en unknown
- 2019-06-25 KR KR1020217010076A patent/KR20220050082A/ko active Search and Examination
- 2019-06-25 JP JP2020572417A patent/JP2022545299A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060019933A1 (en) * | 2004-07-22 | 2006-01-26 | David Boardman | Process for preparing stabilized vitamin D |
JP2014509842A (ja) * | 2011-02-07 | 2014-04-24 | アボット・ラボラトリーズ | β−ヒドロキシ−β−メチルブチラートを含む栄養製品 |
JP2017510629A (ja) * | 2014-03-14 | 2017-04-13 | メタボリック・テクノロジーズ,インコーポレーテッド | 遊離酸形のβ−ヒドロキシ−β−メチル酪酸(HMB)を含有する液体及び食品ならびにその製造法 |
Also Published As
Publication number | Publication date |
---|---|
AU2019453386A1 (en) | 2021-02-18 |
KR20220050082A (ko) | 2022-04-22 |
WO2020263229A1 (en) | 2020-12-30 |
SG11202012984YA (en) | 2021-01-28 |
CA3105039A1 (en) | 2020-12-30 |
CN113056206A (zh) | 2021-06-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7210459B2 (ja) | 老化防止剤及び老化防止方法 | |
US6368617B1 (en) | Dietary supplement | |
JP5545424B2 (ja) | 高齢者の骨格筋量減少を防止又は改善するためのアミノ酸含有組成物 | |
ES2622116T3 (es) | Composición nutricional para la estimulación de la síntesis de proteínas musculares | |
JP5574561B2 (ja) | 総合経腸栄養組成物 | |
US20080317886A1 (en) | Compositions for Preventing and Reducing Delayed Onset Muscle Soreness | |
US20210023096A1 (en) | Nutritional Intervention for Improving Muscular Function and Strength | |
JP2009242413A (ja) | アミノ酸をベースとする医薬 | |
WO2018147385A1 (ja) | 皮膚色素沈着抑制剤 | |
US20220031596A1 (en) | Anti-aging agent and anti-aging method | |
WO2007145239A1 (ja) | アミノ酸組成物を含有する疲労防止剤 | |
JP2007254440A (ja) | 脂質代謝調節剤及び脂質代謝調節食品 | |
US10925845B2 (en) | Stability of vitamin D in β-hydroxy-β-methylbutyrate (HMB) | |
US20040043442A1 (en) | Use of betaine in functional products having blood pressure lowering effects | |
US11490644B2 (en) | Co-Q10, krill oil and vitamin D | |
WO2009136587A1 (ja) | 抗疲労組成物 | |
MXPA06001706A (es) | Jarabe multivitaminico para ninos o adultos jovenes. | |
KR20190058346A (ko) | Chp(시클로-히스프로)를 포함하는 골 손실 질환의 예방, 개선 또는 치료용 조성물 | |
JP2022545299A (ja) | β-ヒドロキシ-β-メチルブチレート(HMB)中のビタミンDの安定性 | |
US20220040205A1 (en) | Stability of vitamin d in beta-hydroxy- beta-methylbutyrate (hmb) | |
EP0354848B1 (fr) | Compositions pharmaceutiques et/ou diététiques contenant de la L-carnitine et de la L-lysine | |
US11173167B2 (en) | Nutritional intervention for improving muscular function and strength | |
EP3836803A1 (en) | Stability of vitamin d in beta-hydroxy- beta-methylbutyrate (hmb) | |
JP3096052B2 (ja) | 脂質代謝調節剤 | |
EP3744323A1 (en) | Composition for preventing or improving nociceptive pain |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220621 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230627 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230927 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20231124 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231221 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20240202 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240527 |