JP7102347B2 - 胃内容排出を増進させるインスリンの使用 - Google Patents
胃内容排出を増進させるインスリンの使用 Download PDFInfo
- Publication number
- JP7102347B2 JP7102347B2 JP2018549878A JP2018549878A JP7102347B2 JP 7102347 B2 JP7102347 B2 JP 7102347B2 JP 2018549878 A JP2018549878 A JP 2018549878A JP 2018549878 A JP2018549878 A JP 2018549878A JP 7102347 B2 JP7102347 B2 JP 7102347B2
- Authority
- JP
- Japan
- Prior art keywords
- insulin
- gastric
- gastric emptying
- day
- subject
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 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 title claims description 488
- 108090001061 Insulin Proteins 0.000 title claims description 245
- 102000004877 Insulin Human genes 0.000 title claims description 244
- 229940125396 insulin Drugs 0.000 title claims description 244
- 230000030136 gastric emptying Effects 0.000 title claims description 64
- 239000000203 mixture Substances 0.000 claims description 77
- 230000002496 gastric effect Effects 0.000 claims description 45
- 206010021518 Impaired gastric emptying Diseases 0.000 claims description 42
- 230000037396 body weight Effects 0.000 claims description 26
- 208000012895 Gastric disease Diseases 0.000 claims description 21
- 235000016709 nutrition Nutrition 0.000 claims description 21
- 208000018773 low birth weight Diseases 0.000 claims description 14
- 231100000533 low birth weight Toxicity 0.000 claims description 14
- 230000001737 promoting effect Effects 0.000 claims description 13
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 6
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 5
- 101001011741 Bos taurus Insulin Proteins 0.000 claims description 2
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 claims description 2
- 208000018556 stomach disease Diseases 0.000 claims description 2
- 238000000034 method Methods 0.000 description 38
- 238000011282 treatment Methods 0.000 description 30
- 239000008194 pharmaceutical composition Substances 0.000 description 26
- 230000001225 therapeutic effect Effects 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 235000013350 formula milk Nutrition 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 210000002784 stomach Anatomy 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 17
- 229940079593 drug Drugs 0.000 description 16
- 210000004080 milk Anatomy 0.000 description 16
- 208000001288 gastroparesis Diseases 0.000 description 15
- 239000008267 milk Substances 0.000 description 15
- 235000013336 milk Nutrition 0.000 description 14
- 239000000546 pharmaceutical excipient Substances 0.000 description 13
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 12
- 201000006549 dyspepsia Diseases 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 239000000902 placebo Substances 0.000 description 9
- 239000005913 Maltodextrin Substances 0.000 description 8
- 229920002774 Maltodextrin Polymers 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000003085 diluting agent Substances 0.000 description 8
- 235000013305 food Nutrition 0.000 description 8
- 229940035034 maltodextrin Drugs 0.000 description 8
- 235000015097 nutrients Nutrition 0.000 description 8
- 229940068196 placebo Drugs 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 239000002775 capsule Substances 0.000 description 7
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 230000002708 enhancing effect Effects 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 208000025865 Ulcer Diseases 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- -1 5-chloro-2-oxo-1-benzimidazolinyl Chemical group 0.000 description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 229930003268 Vitamin C Natural products 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000003111 delayed effect Effects 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 210000003238 esophagus Anatomy 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000002604 ultrasonography Methods 0.000 description 4
- 235000019154 vitamin C Nutrition 0.000 description 4
- 239000011718 vitamin C Substances 0.000 description 4
- 208000004998 Abdominal Pain Diseases 0.000 description 3
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 3
- 206010051153 Diabetic gastroparesis Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010067508 Low birth weight baby Diseases 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000004596 appetite loss Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 208000019017 loss of appetite Diseases 0.000 description 3
- 235000021266 loss of appetite Nutrition 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 210000000813 small intestine Anatomy 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 101800001982 Cholecystokinin Proteins 0.000 description 2
- 102100025841 Cholecystokinin Human genes 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 206010020710 Hyperphagia Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 206010030216 Oesophagitis Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 229940107137 cholecystokinin Drugs 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 208000006881 esophagitis Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 230000030135 gastric motility Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 229940125395 oral insulin Drugs 0.000 description 2
- 229940000673 orphan drug Drugs 0.000 description 2
- 239000002859 orphan drug Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000813 peptide hormone Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 210000001187 pylorus Anatomy 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000036186 satiety Effects 0.000 description 2
- 235000019627 satiety Nutrition 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 235000021195 test diet Nutrition 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- NWWGENWLVIEAAQ-UHFFFAOYSA-N 1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidine Chemical compound C1C(OC)CCCN1CCCOC1=CC=C(F)C=C1 NWWGENWLVIEAAQ-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 240000002900 Arthrospira platensis Species 0.000 description 1
- 235000016425 Arthrospira platensis Nutrition 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-IGMARMGPSA-N Carbon-12 Chemical compound [12C] OKTJSMMVPCPJKN-IGMARMGPSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 208000033293 Jejunal fistula Diseases 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229940127470 Lipase Inhibitors Drugs 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 206010051606 Necrotising colitis Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010029957 Obstruction gastric Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 201000000660 Pyloric Stenosis Diseases 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- 241000657513 Senna surattensis Species 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 229930006000 Sucrose 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
- 241000282887 Suidae Species 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 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 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical group C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 1
- 229960005132 cisapride Drugs 0.000 description 1
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960001253 domperidone Drugs 0.000 description 1
- FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 208000008386 gastric outlet obstruction Diseases 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000004083 gastrointestinal agent Substances 0.000 description 1
- 229940127227 gastrointestinal drug Drugs 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 235000021125 infant nutrition Nutrition 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229960004503 metoclopramide Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 208000024335 physical disease Diseases 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 235000013406 prebiotics Nutrition 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229940082787 spirulina Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229930003231 vitamin Natural products 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
- 230000003442 weekly effect Effects 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Physiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Inorganic Chemistry (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
Description
本出願は、2016年3月24日に出願された米国仮特許出願第62/312,473号の優先権を主張し、その全体が参照により本明細書に組み込まれる。
(i)インスリン、または、その等価物、及び、医薬として許容可能な担体、賦形剤、または、希釈剤を含む医薬組成物、及び
(ii)当該医薬組成物の使用に関する指示書面、を含む。
(i)インスリン、または、その等価物、及び、経口用途に適した担体、賦形剤、または、希釈剤を含む栄養組成物、及び
(ii)当該組成物の使用に関する指示書面、を含む。
胃内容排出を測定するための様々な試験が開発されている。40年以上前に初めて報告がされて以来、シンチグラフィー評価は、広くに普及しており、胃不全麻痺の診断のための「ゴールデンスタンダード」となっている(Abell TL.,The American Journal of Gastroenterology,vol.103,no.3,pp.753-763,2008)。初期の段階より、研究者たちは、胃内容排出速度の決定に関して、体積、カロリー含量、栄養組成、及び、粘稠度の重要性を認識していた。ばらつきを最小限に抑えて、比較を可能にするために、当該試験は、予め定められた容量とカロリー負荷を使用すべきであり、また、4時間以上かけて実施すべきである。このような手法を用いて、繰り返し試験を行うと、対象者の間で著しい変化があっても、許容可能な個体内再現性を示すようになる。
本開示は、インスリンを必要とする対象に対してインスリンを投与することを含む、胃内容排出を増進する方法を提供する。
新生児集中治療室において、胃内残留物(GR)の評価を用いて、授乳後の異なる時点での胃内に残存している乳量を測定し、そして、胃内容排出(GE)の指標として使用する。
インフォームドコンセント文書(ICF)への署名後に、下記の調査基準を満たす適格早産児の両親に対し、研究への参加を促した。両親が研究への不参加を選択した早産児と同じようにして、乳児を新生児病棟に入院させた。これらの乳児は、2つの処置群、試験群としてインスリンを含有する調査製品、それに、コントロール群としてのプラセボ補助食品の内の一方に無作為に割り当てた。両親、乳児の治療にあたる医療チーム、及び、研究モニターには、処置群を知らせなかった。試験の1日目から、試験群の乳児には、授乳準備の整った(RTF)早産児用Materna調製乳と、そこに混ぜたインスリンを与え、コントロール群には、同じRTF早産児用Materna調製乳と、そこに混ぜたプラセボ補助食品を与えた。
この研究に含めるには、下記の基準を満たさなければならなかった。
1.在胎期間26~33週で産まれた早産児。在胎期間は、妊娠日と初期の胎児超音波検査とを照合する(±2週間)。
2.出生体重≧750グラム。
3.生後日数≦7日。
4.登録時の吸入酸素の割合が≦0.60。
5.乳児の心臓血管が安定状態にある。
6.調査1日目以降、授乳しない。
7.分娩中に、心臓及び胸部の圧迫、またはいずれかの蘇生薬が乳児に施されていない。
8.インフォームドコンセントの書類に両親または法定後見人が署名した。
下記の基準の1つ以上を満たす乳児は、この研究から除外した。
1.在胎期間が<26週または>33週である早産児。在胎期間は、妊娠日と初期の胎児超音波検査とを照合する(±2週間)。
2.出生体重<750グラム。
3.生後日数>7日。
4.登録時の吸入酸素の割外が>0.60。
5.乳児の心臓血管が不安定である。
6.調査1日目以降に授乳を行う。
7.重大な先天的形成異常。登録前に、遺伝性代謝障害または内分泌障害と診断された乳児(登録後に診断されたが、先天的であることが知られている障害を含む)。
8.登録前に、感染の疑いの指数が高かった。
9.壊死性腸炎を発現しているか、または、壊死性腸炎の疑いのある乳児。
10.妊娠糖尿病。
11.乳児がインスリンの処置を受けている。
12.本研究参加時に、いずれかの理由でNPO(絶食)していた。
13.分娩中に、心臓及び胸部の圧迫、または、いずれかの蘇生薬が乳児に施された。
14.別の臨床研究に参加している。
調査製品として、本明細書に開示した当該インスリン組成物とプラセボがある。このインスリン組成物は、90mlの授乳準備の整った(RTF)早産児用調製乳(製造者:Nestle Germany、輸入者:Materna Laboratories、イスラエル)との混合を意図している。この調製乳に当該インスリンを加えると、当該調製乳は、400μU/調製乳mlの濃度のインスリンを含む。
(a)2つのジスルフィド結合によって結合された2本のポリペプチド鎖からなる巨大タンパク質(5,800ダルトン)であるヒトインスリン。インスリンは、1ml当たりナノグラムの濃度で哺乳動物の乳に存在する天然の健康増進成分である。インスリンを、真性糖尿病と診断された個体に対して、治療用量で注射するときは、ペプチドホルモンとしても分類される。
(b)多糖の混合物であり、デンプンの部分加水分解によって生成されるマルトデキストリン。マルトデキストリンは、乳児用調製乳の成分として広く用いられており、液体に速やかに溶解する。
(c)ヒトの必須栄養素であるビタミンCまたはL-アスコルビン酸。生物において、アスコルビン酸塩は、身体を酸化ストレスから保護するとともに、幾つかの生体酵素反応における補要因であるので、抗酸化物質である。当該インスリン製剤において、ビタミンCは、インスリン酸化の指示薬として使用されている。
乳児ごとに目印をつけた研究対象の袋(0.5gのインスリン組成物/プラセボを含有しており、当該インスリン組成物は、全体で約36mUのインスリンを含有している)の中身を、新生児集中治療室(NICU)の看護師が、各授乳の直前に、RTF早産児用Materna調製乳の90mlのガラス瓶に入れた。一旦入れ終わったら、瓶を閉じて、よく振って、添加物を完全に溶解させた。授乳ごとに、乳児には、新たな90mlのガラス瓶+添加物を与えた。標準的な哺乳瓶と乳首を用いた。乳児への授乳を終えたら、残存した調製乳は、研究室での使用に限って、ガラス瓶で24時間保存した。乳児の状態が安定しており、かつ、健康であることが確認できた場合には、瓶を破棄するか、あるいは、スポンサーに通知して、検査のために瓶を回収してもらった。
上記述のようにしてインスリンで処置をした双生児について、胃内残留物の測定値が、0ml/体重kg未満(図2及び表1)、または、2ml/kg(図1及び表2)未満に達するまでの日数を調べた。インスリンで処置をした双生児は、コントロールの乳児双生児と比較して、ほとんどにおいて(それぞれ、図1(p=0.031)、及び、図2(p=0.074))、胃内残留物が、2ml/kgまたは0ml/kg未満に到達した。表1及び表2に、結果をまとめた。インスリンを経腸投与すると、胃内残留物が、0mg/体重kg、または、<2ml/体重kgに到達するまでの日数は、コントロールの処置を受けた乳児と比較して、著しく改善した。
単生児に関して、胃内残留物の測定値が、2ml/体重kg未満に達した時点(図3)と、胃内残留物が放出されなくなるまでの日数(表3)とを調べた。図3に示したように、インスリンで処置した単生児は、コントロールよりも早くに、2ml/kg未満の胃内残留物に達した(P=0.121)。
胃内容排出に関するインスリン処置の効果をさらに検証するために、胃不全麻痺の患者を、本開示に従ってインスリンで処置し、そして、Cappello G et al.(Am J Gastroenterol.2000 Nov;95(11):3097-100)に従って呼気試験を実施する。胃不全麻痺の患者を、2つの群に無作為に分け、その内の一方の群では、1週間、1U/体重kg/日のインスリンを、毎日、経口投与して処置し、そして、他方の群は、コントロールとする。実験の当日に、固形試験食(すなわち、13C-オクタン酸を含む卵黄)に溶解する非放射性安定同位体13C物質を含む食事を患者に与える。次いで、呼気に含まれる13CO2を測定する。ベースラインに加えて、240分の期間にわたって30分ごとに、呼気標本を採取する。呼気13CO2の測定は、質量分析、または、赤外分光法で行う。呼気標本に含まれる13CO2の出現の遅延は、胃と十二指腸との間の固形物の移動速度の減少に起因するものであり、すなわち、胃内容排出は、飲食物が迅速に吸収される際の律速段階になっている。
Claims (13)
- 約200μU/mL~約4000μU/mLの濃度でインスリンを含む、それを必要としている低出生体重児において胃内容排出を増進するのに使用するための組成物であって、経腸投与される組成物。
- 前記低出生体重児が、胃疾患に罹患している、請求項1に記載の組成物。
- 前記胃疾患が、胃内容排出遅延を特徴とする、請求項2に記載の組成物。
- 前記胃内容排出が、2ml/kg体重よりも少ない胃内残留物に達することと定義される、請求項1に記載の組成物。
- 前記インスリンが、ヒトインスリン及びウシインスリンからなる群から選択される哺乳動物インスリンである、請求項1~4のいずれか1項に記載の組成物。
- 前記インスリンが、組換えインスリンまたは合成インスリンである、請求項1~4のいずれか1項に記載の組成物。
- 前記インスリンが、封入材料中に封入されている、請求項1~6のいずれか1項に記載の組成物。
- 前記インスリンが、経腸投与のための組成物に製剤化されている、請求項1~7のいずれか1項に記載の組成物。
- 経口投与用に製剤化されている、請求項8に記載の組成物。
- 約0.001U/kg/日~約0.5U/kg/日というインスリンの総量を前記低出生体重児にもたらす、請求項1に記載の組成物。
- 栄養組成物である、請求項1~10のいずれか1項に記載の組成物。
- 前記低出生体重児が、早産児である、請求項1~11のいずれか1項に記載の組成物。
- 前記低出生体重児が、26~32週の在胎期間で出生している、請求項12に記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662312473P | 2016-03-24 | 2016-03-24 | |
US62/312,473 | 2016-03-24 | ||
PCT/US2017/024053 WO2017165789A1 (en) | 2016-03-24 | 2017-03-24 | Use of insulin for promoting gastric emptying |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2019509317A JP2019509317A (ja) | 2019-04-04 |
JP2019509317A5 JP2019509317A5 (ja) | 2020-05-07 |
JP7102347B2 true JP7102347B2 (ja) | 2022-07-19 |
Family
ID=59900798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018549878A Active JP7102347B2 (ja) | 2016-03-24 | 2017-03-24 | 胃内容排出を増進させるインスリンの使用 |
Country Status (19)
Country | Link |
---|---|
US (1) | US10046032B2 (ja) |
EP (1) | EP3432861B1 (ja) |
JP (1) | JP7102347B2 (ja) |
KR (1) | KR20180123114A (ja) |
CN (1) | CN109152733A (ja) |
AR (1) | AR108753A1 (ja) |
AU (1) | AU2017237164A1 (ja) |
BR (1) | BR112018069444A2 (ja) |
CA (1) | CA3018215C (ja) |
ES (1) | ES2957891T3 (ja) |
HR (1) | HRP20230972T1 (ja) |
HU (1) | HUE062950T2 (ja) |
IL (1) | IL261898A (ja) |
MX (1) | MX2018011512A (ja) |
PL (1) | PL3432861T3 (ja) |
RS (1) | RS64623B1 (ja) |
RU (1) | RU2018133604A (ja) |
SG (1) | SG11201808154XA (ja) |
WO (1) | WO2017165789A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG11201808154XA (en) | 2016-03-24 | 2018-10-30 | Nutrinia Ltd | Use of insulin for promoting gastric emptying |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000050793A (ja) | 1998-08-07 | 2000-02-22 | Meiji Milk Prod Co Ltd | 人工乳組成物 |
JP2002516880A (ja) | 1998-06-05 | 2002-06-11 | テクニオン リサーチ アンド デベロップメント ファウンデーション リミテッド | インスリンを補った乳児用調製乳 |
JP2004525857A (ja) | 2000-04-19 | 2004-08-26 | ジョンズ・ホプキンス・ユニバーシティ | 胃腸疾患の予防および治療のための方法 |
JP2007520202A (ja) | 2003-06-20 | 2007-07-26 | ニュートリニア・リミテッド | 生物活性化合物の保護方法及びそれを含む組成物 |
US20070225211A1 (en) | 2004-06-02 | 2007-09-27 | Technion Research & Developement | Methods and Formulations for Increasing Intestinal Function |
US20070248652A1 (en) | 2004-05-24 | 2007-10-25 | Nutrinia Ltd. | Nutritional Food and Feed, Compostition, Processing and Method of Use |
JP2010528651A (ja) | 2007-06-07 | 2010-08-26 | ニュートリニア リミテッド | 家禽の体重増量を向上させるための手段および方法 |
JP2015514747A (ja) | 2012-04-18 | 2015-05-21 | ニュートリニア リミテッド | 乳児の発育促進 |
US20150209412A1 (en) | 2012-05-31 | 2015-07-30 | Nutrinia Ltd. | Insulin-containing infant formula |
Family Cites Families (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988001506A1 (en) | 1986-08-28 | 1988-03-10 | Thomas Ko Sai Ying | Microgranular preparation useful in the delivery of biologically active materials to the intestinal regions of animals |
US5356625A (en) | 1986-08-28 | 1994-10-18 | Enzacor Properties Limited | Microgranular preparation useful in the delivery of biologically active materials to the intestinal regions of animals |
FR2606597B1 (fr) | 1986-11-17 | 1989-01-27 | Rhone Poulenc Sante | Nouvelle composition pour l'alimentation des ruminants contenant une substance biologiquement active et sa preparation |
US4944944A (en) | 1987-11-19 | 1990-07-31 | Oklahoma Medical Research Foundation | Dietary compositions and methods using bile salt-activated lipase |
US5013569A (en) | 1990-05-21 | 1991-05-07 | Century Laboratories, Inc. | Infant formula |
US5418010A (en) | 1990-10-05 | 1995-05-23 | Griffith Laboratories Worldwide, Inc. | Microencapsulation process |
DE4100920A1 (de) | 1991-01-15 | 1992-07-16 | Degussa | Wirkstoffzubereitung zur oralen verabreichung an wiederkaeuer |
US5160742A (en) | 1991-12-31 | 1992-11-03 | Abbott Laboratories | System for delivering an active substance for sustained release |
US5360614A (en) | 1993-04-26 | 1994-11-01 | The Estee Corporation | Method of controlling the release of carbohydrates by encapsulation and composition therefor |
US5405637A (en) | 1993-06-30 | 1995-04-11 | Bristol-Myers Squibb Company | Milk protein partial hydrolysate and infant formula containing same |
US5531989A (en) | 1994-10-28 | 1996-07-02 | Metagenics, Inc. | Immunoglobulin and fiber-containing composition for human gastrointestinal health |
EP0750854B1 (en) | 1995-06-29 | 2001-10-24 | Societe Des Produits Nestle S.A. | Process for encapsulating a core material with a polymer by high-pressure treatment |
JPH10155428A (ja) | 1996-12-04 | 1998-06-16 | Shida Kanzume Kk | 毛づや改善剤及び毛づやの改善方法、並びに健康食品 |
CN1191828C (zh) | 1997-03-27 | 2005-03-09 | 布里斯托尔-迈尔斯斯奎布公司 | 二十二碳六烯酸和花生四烯酸促进不足月婴儿生长的用途 |
JPH119196A (ja) | 1997-06-24 | 1999-01-19 | Meiji Seika Kaisha Ltd | キトサンによる家畜の損耗防止の方法 |
DE69816778T2 (de) | 1997-09-09 | 2004-04-15 | Lyotropic Therapeutics, Inc. | Beschichtete teilchen, methode zu ihrer herstellung und verwendung |
US6638621B2 (en) | 2000-08-16 | 2003-10-28 | Lyotropic Therapeutics, Inc. | Coated particles, methods of making and using |
US6399090B1 (en) | 1998-06-05 | 2002-06-04 | Insotech Ltd. | Insulin supplemented infant formula |
JP2000116320A (ja) | 1998-10-13 | 2000-04-25 | Bingu Gure:Kk | 乳酸菌カプセル入りヨーグルト及びその製造方法 |
GB2345836A (en) | 1999-01-25 | 2000-07-26 | Charleville Res | Animal milk replacer |
US7374779B2 (en) | 1999-02-26 | 2008-05-20 | Lipocine, Inc. | Pharmaceutical formulations and systems for improved absorption and multistage release of active agents |
US6548043B1 (en) | 1999-08-03 | 2003-04-15 | Metabolic Solutions, Inc. | Measurement of gastric emptying |
CA2409286C (en) | 2000-05-25 | 2012-05-15 | Societe Des Produits Nestle S.A. | Dog & cat food compositions having a probiotic lactobacillus strain |
DE60018586T2 (de) | 2000-12-15 | 2006-04-06 | Quest International B.V. | Eine Feuchtigkeit- und Sauerstoff-stabile Zusammensetzung und Verfahren zur Herstellung |
JP2002209513A (ja) | 2000-12-15 | 2002-07-30 | Bingu-Gure:Kk | 栄養成分を含有する多数のカプセル入り強化牛乳 |
AUPR272901A0 (en) | 2001-01-25 | 2001-02-22 | Gainful Plan Limited | Method of preparing biological materials and preparations produced using same |
WO2002091860A1 (fr) | 2001-05-14 | 2002-11-21 | Vasily Petrovich Andreichuk | Additif alimentaire biologiquement actif et additif fourrager biologiquement actif servant a prevenir la carence en iode et a optimiser le metabolisme de l'iode, produits alimentaires et fourragers contenant ces additifs |
CA2449202A1 (en) | 2001-05-23 | 2002-11-28 | Institut National De La Recherche Scientifique | Biocompatible compositions as carriers or excipients for pharmaceutical and nutraceutical formulations and for food protection |
US20030044458A1 (en) | 2001-08-06 | 2003-03-06 | Curtis Wright | Oral dosage form comprising a therapeutic agent and an adverse-effect agent |
US6951655B2 (en) | 2001-10-11 | 2005-10-04 | Imi Biomed, Inc. | Pro-micelle pharmaceutical compositions |
US20030175382A1 (en) | 2002-03-14 | 2003-09-18 | Dally Vernetta L. | Heat released encapsulated yeast |
US20030175403A1 (en) | 2002-03-14 | 2003-09-18 | Gurin Michael H. | Potentiated bioactive additives and method of use |
CN1656205A (zh) | 2002-07-01 | 2005-08-17 | 诺和酶股份有限公司 | 颗粒的稳定 |
US6835397B2 (en) | 2002-12-23 | 2004-12-28 | Balchem Corporation | Controlled release encapsulated bioactive substances |
GB0502795D0 (en) | 2005-02-10 | 2005-03-16 | Univ Cambridge Tech | Treatment of very low birthweight (vlbw) infants |
US9259456B2 (en) | 2005-09-06 | 2016-02-16 | Oramed Pharmaceuticals Inc. | Methods and compositions for oral administration of proteins |
US7943733B2 (en) | 2007-12-20 | 2011-05-17 | University Of Southern California | Spacers to increase the expression of recombinant fusion proteins |
ES2603328T3 (es) | 2010-10-21 | 2017-02-27 | Swedish Orphan Biovitrum Ab (Publ) | Método para incrementar la tasa de crecimiento de lactantes humanos |
EP2520298A1 (en) | 2011-05-03 | 2012-11-07 | Assistance Publique, Hopitaux De Paris | Pharmaceutical composition comprising sulfonylureas (glibenclamide) or meglitinides for use for treating hyperglycaemia or for promoting growth of a premature infant |
SG11201808154XA (en) | 2016-03-24 | 2018-10-30 | Nutrinia Ltd | Use of insulin for promoting gastric emptying |
-
2017
- 2017-03-24 SG SG11201808154XA patent/SG11201808154XA/en unknown
- 2017-03-24 KR KR1020187029772A patent/KR20180123114A/ko not_active IP Right Cessation
- 2017-03-24 CN CN201780030498.8A patent/CN109152733A/zh active Pending
- 2017-03-24 RU RU2018133604A patent/RU2018133604A/ru not_active Application Discontinuation
- 2017-03-24 AU AU2017237164A patent/AU2017237164A1/en not_active Abandoned
- 2017-03-24 US US15/468,965 patent/US10046032B2/en active Active
- 2017-03-24 MX MX2018011512A patent/MX2018011512A/es unknown
- 2017-03-24 BR BR112018069444A patent/BR112018069444A2/pt not_active Application Discontinuation
- 2017-03-24 WO PCT/US2017/024053 patent/WO2017165789A1/en active Application Filing
- 2017-03-24 CA CA3018215A patent/CA3018215C/en active Active
- 2017-03-24 PL PL17771247.8T patent/PL3432861T3/pl unknown
- 2017-03-24 ES ES17771247T patent/ES2957891T3/es active Active
- 2017-03-24 HR HRP20230972TT patent/HRP20230972T1/hr unknown
- 2017-03-24 RS RS20230856A patent/RS64623B1/sr unknown
- 2017-03-24 HU HUE17771247A patent/HUE062950T2/hu unknown
- 2017-03-24 EP EP17771247.8A patent/EP3432861B1/en active Active
- 2017-03-24 JP JP2018549878A patent/JP7102347B2/ja active Active
- 2017-03-27 AR ARP170100743A patent/AR108753A1/es unknown
-
2018
- 2018-09-20 IL IL261898A patent/IL261898A/en unknown
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002516880A (ja) | 1998-06-05 | 2002-06-11 | テクニオン リサーチ アンド デベロップメント ファウンデーション リミテッド | インスリンを補った乳児用調製乳 |
JP2000050793A (ja) | 1998-08-07 | 2000-02-22 | Meiji Milk Prod Co Ltd | 人工乳組成物 |
JP2004525857A (ja) | 2000-04-19 | 2004-08-26 | ジョンズ・ホプキンス・ユニバーシティ | 胃腸疾患の予防および治療のための方法 |
JP2007520202A (ja) | 2003-06-20 | 2007-07-26 | ニュートリニア・リミテッド | 生物活性化合物の保護方法及びそれを含む組成物 |
US20070248652A1 (en) | 2004-05-24 | 2007-10-25 | Nutrinia Ltd. | Nutritional Food and Feed, Compostition, Processing and Method of Use |
US20070225211A1 (en) | 2004-06-02 | 2007-09-27 | Technion Research & Developement | Methods and Formulations for Increasing Intestinal Function |
JP2010528651A (ja) | 2007-06-07 | 2010-08-26 | ニュートリニア リミテッド | 家禽の体重増量を向上させるための手段および方法 |
JP2015514747A (ja) | 2012-04-18 | 2015-05-21 | ニュートリニア リミテッド | 乳児の発育促進 |
US20150209412A1 (en) | 2012-05-31 | 2015-07-30 | Nutrinia Ltd. | Insulin-containing infant formula |
Non-Patent Citations (1)
Title |
---|
R Shulman,Effect of enteral administration of insulin on intestinal development and feeding tolerance in preterm infants: a pilot study,Arch Dis Child Fetal Neonatal Ed. 2002 Mar; 86(2): F131-F133.,2002年 |
Also Published As
Publication number | Publication date |
---|---|
PL3432861T3 (pl) | 2023-12-18 |
JP2019509317A (ja) | 2019-04-04 |
US10046032B2 (en) | 2018-08-14 |
HRP20230972T1 (hr) | 2023-12-08 |
BR112018069444A2 (pt) | 2019-10-08 |
WO2017165789A1 (en) | 2017-09-28 |
SG11201808154XA (en) | 2018-10-30 |
EP3432861B1 (en) | 2023-07-12 |
ES2957891T3 (es) | 2024-01-29 |
RS64623B1 (sr) | 2023-10-31 |
CA3018215A1 (en) | 2017-09-28 |
EP3432861A1 (en) | 2019-01-30 |
CA3018215C (en) | 2023-10-03 |
KR20180123114A (ko) | 2018-11-14 |
IL261898A (en) | 2018-10-31 |
EP3432861C0 (en) | 2023-07-12 |
HUE062950T2 (hu) | 2023-12-28 |
CN109152733A (zh) | 2019-01-04 |
AR108753A1 (es) | 2018-09-26 |
EP3432861A4 (en) | 2019-10-23 |
AU2017237164A1 (en) | 2018-10-11 |
MX2018011512A (es) | 2019-02-07 |
US20170319663A1 (en) | 2017-11-09 |
RU2018133604A (ru) | 2020-04-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Littlewood et al. | Diagnosis and treatment of intestinal malabsorption in cystic fibrosis | |
CN113713084A (zh) | 一种组合物在制备治疗骨关节疼痛和中老年骨质疏松的药物中的应用 | |
JP2017515881A (ja) | 新生児の微生物叢の補充 | |
JP3614427B2 (ja) | 消化管吸収を増大する方法 | |
JP7102347B2 (ja) | 胃内容排出を増進させるインスリンの使用 | |
JP6177310B2 (ja) | 乳児の発育促進 | |
EC | Neonatal mythbusters: evaluating the evidence for and against pharmacologic and nonpharmacologic management of gastroesophageal reflux | |
AU2013250712A1 (en) | Growth enhancement of infants | |
Kaur et al. | Comparison of three nursing positions for reducing gastric residuals in preterm neonates: a randomized crossover trial | |
Playford et al. | Bovine Colostrum: Its Constituents and Uses. Nutrients. 2021; 13: 265 | |
Juul | Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates | |
Signorino et al. | Worsening of Congenital Hypothyroidism After Start of Carob-bean Gum Thickened Formula: Is There a Link? A Case Report | |
Dupont | Gastroesophageal reflux (GER) in the preterm baby | |
Batchelor | Paediatric development: gastrointestinal | |
JP2001226285A (ja) | 小腸成長促進組成物 | |
AU2022391767A1 (en) | Methods and compositions for treating musculoskeletal diseases, treating inflammation, and managing symptoms of menopause | |
WO2023092150A1 (en) | Methods and compositions for treating musculoskeletal diseases, treating inflammation, and managing symptoms of menopause | |
JP2022513524A (ja) | 低fodmap食を使用してヒトを治療するための組成物および方法 | |
ZHANG et al. | Effects of physiological factors on small intestinal transit time | |
JP2023553548A (ja) | 睡眠パターンの成熟又は改善の支援に使用するためのヒト母乳オリゴ糖 | |
Symonds | Non-invasive assessment of gastrointestinal function using breath test technology: investigations in health and disease. | |
JP2010077102A (ja) | 高齢者向け機能食品および医薬組成物 | |
Sreekanth et al. | Pharmaceutical and Nano Sciences | |
Risser et al. | Enteral Nutrition | |
AbuSabha | ENTERAL NEEDS OF PRETERM INFANTS |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200323 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200323 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20201221 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210112 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210408 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20210519 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20210519 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210709 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20210709 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20211102 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220128 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220614 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220706 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7102347 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |