TW202028330A - 水溶性含矽顆粒 - Google Patents
水溶性含矽顆粒 Download PDFInfo
- Publication number
- TW202028330A TW202028330A TW108140859A TW108140859A TW202028330A TW 202028330 A TW202028330 A TW 202028330A TW 108140859 A TW108140859 A TW 108140859A TW 108140859 A TW108140859 A TW 108140859A TW 202028330 A TW202028330 A TW 202028330A
- Authority
- TW
- Taiwan
- Prior art keywords
- water
- soluble
- particles
- silicon
- starch
- Prior art date
Links
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229910052710 silicon Inorganic materials 0.000 title claims abstract description 46
- 239000010703 silicon Substances 0.000 title claims abstract description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 239000008187 granular material Substances 0.000 title claims abstract description 14
- 229920002472 Starch Polymers 0.000 claims abstract description 42
- 235000019698 starch Nutrition 0.000 claims abstract description 41
- 239000008107 starch Substances 0.000 claims abstract description 39
- 150000003377 silicon compounds Chemical class 0.000 claims abstract description 31
- 239000000463 material Substances 0.000 claims abstract description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 5
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims abstract description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 2
- 239000002245 particle Substances 0.000 claims description 96
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 33
- 229960001231 choline Drugs 0.000 claims description 13
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 13
- 238000005469 granulation Methods 0.000 claims description 13
- 230000003179 granulation Effects 0.000 claims description 13
- 239000003381 stabilizer Substances 0.000 claims description 13
- 239000012669 liquid formulation Substances 0.000 claims description 12
- 235000013361 beverage Nutrition 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 229920001353 Dextrin Polymers 0.000 claims description 7
- 239000004375 Dextrin Substances 0.000 claims description 7
- 235000019425 dextrin Nutrition 0.000 claims description 7
- 201000004384 Alopecia Diseases 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- -1 polyphenol compounds Chemical class 0.000 claims description 6
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 6
- 229920002774 Maltodextrin Polymers 0.000 claims description 5
- 239000005913 Maltodextrin Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 5
- 229940035034 maltodextrin Drugs 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 230000003676 hair loss Effects 0.000 claims description 4
- 235000016709 nutrition Nutrition 0.000 claims description 4
- 206010065687 Bone loss Diseases 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 239000006052 feed supplement Substances 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 238000006116 polymerization reaction Methods 0.000 claims description 3
- 235000013824 polyphenols Nutrition 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 230000009759 skin aging Effects 0.000 claims description 3
- CKNYEUXAXWTAPK-UHFFFAOYSA-N 4-octoxy-4-oxobutanoic acid Chemical compound CCCCCCCCOC(=O)CCC(O)=O CKNYEUXAXWTAPK-UHFFFAOYSA-N 0.000 claims description 2
- 231100000360 alopecia Toxicity 0.000 claims description 2
- 230000008355 cartilage degradation Effects 0.000 claims description 2
- 235000015872 dietary supplement Nutrition 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004549 water soluble granule Substances 0.000 claims 3
- 150000001299 aldehydes Chemical class 0.000 claims 2
- 150000002989 phenols Chemical class 0.000 claims 2
- 229920005862 polyol Polymers 0.000 claims 2
- 150000003077 polyols Chemical class 0.000 claims 2
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000006185 dispersion Substances 0.000 claims 1
- 238000005538 encapsulation Methods 0.000 claims 1
- 235000012239 silicon dioxide Nutrition 0.000 description 31
- 229940032147 starch Drugs 0.000 description 26
- 238000009472 formulation Methods 0.000 description 23
- 229920000881 Modified starch Polymers 0.000 description 17
- 235000019426 modified starch Nutrition 0.000 description 16
- 239000004368 Modified starch Substances 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 239000007788 liquid Substances 0.000 description 13
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 11
- 238000000673 graphite furnace atomic absorption spectrometry Methods 0.000 description 11
- 239000011733 molybdenum Substances 0.000 description 11
- 229910052750 molybdenum Inorganic materials 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 238000009826 distribution Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 8
- 235000019743 Choline chloride Nutrition 0.000 description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 8
- 229910052782 aluminium Inorganic materials 0.000 description 8
- 229960003178 choline chloride Drugs 0.000 description 8
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 8
- 238000005029 sieve analysis Methods 0.000 description 8
- 239000000178 monomer Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000007921 spray Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 239000007937 lozenge Substances 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 239000012159 carrier gas Substances 0.000 description 4
- 239000012876 carrier material Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 238000011020 pilot scale process Methods 0.000 description 4
- 238000006068 polycondensation reaction Methods 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000005563 spheronization Methods 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- GUOCOOQWZHQBJI-UHFFFAOYSA-N 4-oct-7-enoxy-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)OCCCCCCC=C GUOCOOQWZHQBJI-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- SHEYKHMHFCPWCL-UHFFFAOYSA-N disilanyl-hydroxy-methylsilane Chemical compound C[SiH](O)[SiH2][SiH3] SHEYKHMHFCPWCL-UHFFFAOYSA-N 0.000 description 3
- 239000001245 distarch phosphate Substances 0.000 description 3
- 235000013804 distarch phosphate Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 229950004354 phosphorylcholine Drugs 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 150000003248 quinolines Chemical class 0.000 description 3
- 229940080313 sodium starch Drugs 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 240000003183 Manihot esculenta Species 0.000 description 2
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 2
- 229910003902 SiCl 4 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004376 Sucralose Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 238000001479 atomic absorption spectroscopy Methods 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 229960004874 choline bitartrate Drugs 0.000 description 2
- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 239000010439 graphite Substances 0.000 description 2
- 229910002804 graphite Inorganic materials 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000021056 liquid food Nutrition 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
- 239000011859 microparticle Substances 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- FDNAPBUWERUEDA-UHFFFAOYSA-N silicon tetrachloride Chemical compound Cl[Si](Cl)(Cl)Cl FDNAPBUWERUEDA-UHFFFAOYSA-N 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 2
- 235000019408 sucralose Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 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 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- GLCIENYSYGDNIL-UHFFFAOYSA-N (2,3-dichlorophenyl) ethaneperoxoate Chemical compound CC(=O)OOC1=CC=CC(Cl)=C1Cl GLCIENYSYGDNIL-UHFFFAOYSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 description 1
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 description 1
- OXJISOJFVQITNG-UHFFFAOYSA-M 2,4-D choline Chemical compound C[N+](C)(C)CCO.[O-]C(=O)COC1=CC=C(Cl)C=C1Cl OXJISOJFVQITNG-UHFFFAOYSA-M 0.000 description 1
- ZZJFIXMCLZTHQV-UHFFFAOYSA-O 2-carboxyoxyethyl(trimethyl)azanium Chemical compound C[N+](C)(C)CCOC(O)=O ZZJFIXMCLZTHQV-UHFFFAOYSA-O 0.000 description 1
- RPERJPYDELTDMR-UHFFFAOYSA-K 2-hydroxyethyl(trimethyl)azanium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound C[N+](C)(C)CCO.C[N+](C)(C)CCO.C[N+](C)(C)CCO.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O RPERJPYDELTDMR-UHFFFAOYSA-K 0.000 description 1
- MIFGTXFTLQVWJW-UHFFFAOYSA-M 2-hydroxyethyl(trimethyl)azanium;2-hydroxypropanoate Chemical compound CC(O)C([O-])=O.C[N+](C)(C)CCO MIFGTXFTLQVWJW-UHFFFAOYSA-M 0.000 description 1
- BODTUEMDCNOIBJ-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzaldehyde phenol Chemical compound C1(=CC=CC=C1)O.OC1=C(C=C(C=O)C=C1)OC BODTUEMDCNOIBJ-UHFFFAOYSA-N 0.000 description 1
- KZSXRDLXTFEHJM-UHFFFAOYSA-N 5-(trifluoromethyl)benzene-1,3-diamine Chemical compound NC1=CC(N)=CC(C(F)(F)F)=C1 KZSXRDLXTFEHJM-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 229920000107 Acetylated distarch adipate Polymers 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 239000004370 Bleached starch Substances 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920003012 Hydroxypropyl distarch phosphate Polymers 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 235000018290 Musa x paradisiaca Nutrition 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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- MKRNVBXERAPZOP-UHFFFAOYSA-N Starch acetate Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OC(C)=O)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 MKRNVBXERAPZOP-UHFFFAOYSA-N 0.000 description 1
- 239000004355 Starch acetate esterified with vinyl acetate Substances 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 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 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 235000019428 bleached starch Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 229960003257 choline citrate Drugs 0.000 description 1
- 229940075419 choline hydroxide Drugs 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- LERGNLHMQHBKIS-UHFFFAOYSA-N dibutyl-(2-hydroxyethyl)-methylazanium Chemical compound CCCC[N+](C)(CCO)CCCC LERGNLHMQHBKIS-UHFFFAOYSA-N 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000007757 hot melt coating Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000001310 hydroxy propyl distarch phosphate Substances 0.000 description 1
- 235000013825 hydroxy propyl distarch phosphate Nutrition 0.000 description 1
- DVROLKBAWTYHHD-UHFFFAOYSA-N hydroxy propyl distarch phosphate Chemical compound OC1C(O)C(OC)OC(CO)C1OC(O)CCOC1C(OC2C(C(O)C(OC3C(C(OP(O)(=O)OC4C(C(O)C(OC)OC4CO)O)C(C)OC3CO)O)OC2COC2C(C(O)C(OC)C(CO)O2)O)O)OC(CO)C(OC)C1O DVROLKBAWTYHHD-UHFFFAOYSA-N 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000000282 nail Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001254 oxidized starch Substances 0.000 description 1
- 235000013808 oxidized starch Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 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
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000021568 protein beverage Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 125000005624 silicic acid group Chemical group 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- UGTZMIPZNRIWHX-UHFFFAOYSA-K sodium trimetaphosphate Chemical compound [Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 UGTZMIPZNRIWHX-UHFFFAOYSA-K 0.000 description 1
- XDLYMKFUPYZCMA-UHFFFAOYSA-M sodium;4-oct-1-enoxy-4-oxobutanoate Chemical compound [Na+].CCCCCCC=COC(=O)CCC([O-])=O XDLYMKFUPYZCMA-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 235000021055 solid food Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 229940100515 sorbitan Drugs 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 235000019430 starch acetate esterified with vinyl acetate Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/163—Sugars; Polysaccharides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/20—Inorganic substances, e.g. oligoelements
- A23K20/28—Silicates, e.g. perlites, zeolites or bentonites
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K40/00—Shaping or working-up of animal feeding-stuffs
- A23K40/10—Shaping or working-up of animal feeding-stuffs by agglomeration; by granulation, e.g. making powders
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- A23L33/16—Inorganic salts, minerals or trace elements
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/20—Agglomerating; Granulating; Tabletting
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0216—Solid or semisolid forms
- A61K8/022—Powders; Compacted Powders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0216—Solid or semisolid forms
- A61K8/022—Powders; Compacted Powders
- A61K8/0225—Granulated powders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/25—Silicon; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
- A61K8/416—Quaternary ammonium compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/732—Starch; Amylose; Amylopectin; Derivatives thereof
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q3/00—Manicure or pedicure preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/92—Oral administration
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Birds (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physical Education & Sports Medicine (AREA)
- Animal Husbandry (AREA)
- Mycology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
- Fodder In General (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
- Cosmetics (AREA)
Abstract
本發明係關於一種水溶性含矽顆粒，其包含式Yx
Si(OH)4 - x
之矽化合物或其寡聚物，其中Y為視情況經取代之(C1
-C4
)烷基、(C2
-C5
)烯基、(C1
-C4
)烷氧基、胺基且其中x為0-2；及冷水溶性澱粉材料。
Description
本發明係關於一種包含呈生物可用形式之矽化合物之調配物、其製備方法及其用途。
礦物矽之生物可用形式為正矽酸(OSA)，其在稀釋濃度(亦即＜10- 3
M)下化學穩定(Iler 1979)。在較高濃度下，OSA之聚縮合發生，導致寡聚物及聚合物之形成。此等單體之聚縮合形式不為人所吸收(Jugdaohsingh等人2000)然而應由胃酸轉化成OSA以實現在胃-腸道中之吸收。為了抑制該聚縮合，可使用穩定劑。結果為呈生物可用形式之矽酸，亦稱為生物可用矽化合物。亦已提出諸如單甲基三矽醇之單烷基三矽醇化合物作為生物可用矽化合物。
本發明申請人已發明經穩定矽酸之液體與固體調配物兩者，且研發成可商購之產品。液體調配物揭示於EP0743922中，且藉助於擠塑-滾圓技術製備的固體調配物揭示於EP1551763中。固體調配物呈具有在800-1200 µm之間之粒度的微粒形式，其用於填充硬膠囊。此等產物已在各種臨床試驗中經測試，在該等試驗中發現對骨骼、軟骨、毛髮、指甲及皮膚之有益結果。亦已發現，在經口攝入經穩定矽酸之後，所攝取之矽化合物主要發現為血液及尿液中之正矽酸。
將需要提供一種適合於食品、飼料及醫藥應用之生物可用矽酸之固體調配物，其中該劑量為預定義的，該劑量可容易地經液體或飲料溶解成具有低黏度之易於飲用製劑。當患者在旅行時，此類調配物將促成患者順應性及促進其使用。在無分離風險之情況下，亦可將固體調配物與其他營養物、調味劑及/或甜味劑摻合，且亦可置換用擠塑-滾圓技術製成之珠粒。
第一目的為提供此類包含生物可用矽化合物之經改良之固體調配物。
因此，本發明之第一目的為提供一種用於生物可用矽化合物之經改良之固體調配物的製造方法。
本發明之另一目的為提供可溶解於液體中之劑型，且其中有效劑量為預定義的。
本發明之再另一目的為提供作為食品或飼料補充物之用途。
本發明之另一目的為提供適用作藥劑之調配物。
在水溶性含矽顆粒中實現第一目的，該水溶性含矽顆粒包含(1)式Yx
Si(OH)4 - x
之矽化合物或其寡聚物，其中Y為視情況經取代之(C1
-C4
)烷基、(C2
-C5
)烯基、(C1
-C4
)烷氧基、胺基，且其中x為0-2，及(2)冷水溶性澱粉材料。
在用於提供本發明之水溶性含矽顆粒之方法中實現第二目的，該方法包含以下步驟：
- 提供式Yx
Si(OH)4 - x
之矽化合物或其寡聚物之液體調配物，其中Y為視情況經取代之(C1
-C4
)烷基、(C2
-C5
)烯基、(C1
-C4
)烷氧基、胺基，且其中x為0-2，且較佳地x=0；
- 提供冷水溶性澱粉材料，及
- 混合該液體調配物及該冷水溶性澱粉材料，使得該矽化合物吸附於該澱粉材料上且形成含矽顆粒。
亦可在藉由本發明方法獲得之顆粒中實現第一目的。
在包含本發明之顆粒的草本或營養組合物，諸如劑型或封裝中，在其作為食品補充物或飼料補充物之用途中，及在用於預防、抑制及/或治療骨質流失及軟骨退化相關疾病、毛髮指甲品質喪失、禿髮及皮膚老化疾病中之顆粒中實現其他目的。
此外，在預防、抑制及/或治療骨質流失及軟骨退化相關疾病、毛髮指甲品質喪失、禿髮及皮膚老化疾病之方法中實現另一目的，該方法包含使用本發明之水溶性含矽顆粒，及/或包含該顆粒之任何劑型或封裝。在一較佳實施例中，將顆粒或其固體劑型在經口投與消費者或患者之前，溶解或分散於飲料中。
本發明之發明人已發現可藉由混合矽化合物之液體調配物與冷水溶性澱粉材料來製備諸如正矽酸或其寡聚物之含有矽化合物之水溶性顆粒。此為一種切實可行的方法，其避免將單獨的黏合劑溶液用於進入造粒製程中之固體部分。除此之外，顆粒為用於與其他營養物質及/或固體食物產品整合之適合形式。此外，所得顆粒結果為高度有利的，因為消費者或患者可在使用之前將顆粒溶解於飲料。在本文中，矽化合物之味道藉由飲料味道抑制。且令本發明人出乎意料的是，顆粒中之矽酸不進一步聚合成不能再在胃-腸道中吸收之形式。
術語『冷水溶性澱粉』在澱粉領域中本身為已知，且關於澱粉材料，當在環境溫度下將該等澱粉材料添加至水中時，其表現顆粒結構之完全破壞及膠態分散液或甚至溶液或表觀溶液之形成。改質處理之非限制性實例為酯化，可能與以下各者組合：鹽形成；醇-鹼處理，諸如M.J. Jivan等人,J . Food Science Technology
(2014年3月), 51(3), 601-605中所揭示；在高溫高壓下在含水醇中混合澱粉；使用氫氧化鈉與尿素之混合物作為水解劑之澱粉水解；糊精化。
適合地，改質澱粉材料在室溫(25℃)下之溶解度百分比至少為50 wt%，更佳地至少為60 wt%或甚至至少為70 wt%。基於藉由在1,000 rpm下在室溫下使用旋轉振盪器混合45分鐘所產生之改質澱粉之1 wt%水性懸浮液量測溶解度百分比。使用離心處理(1,200 g速度持續15分鐘)自懸浮液分離出上清液，且隨後乾燥上清液(6小時，105℃)。溶解度百分比按上清液中之固體質量與樣本質量之比率乘以100%計算。
較佳載體材料包括一或多種經化學改質之澱粉材料，諸如糊精、經酸處理之澱粉、經鹼改質之澱粉、漂白澱粉、氧化澱粉、經酶處理之澱粉。較佳類別之改質澱粉材料為酯化澱粉，諸如磷酸單澱粉、雙澱粉甘油；經三偏磷酸鈉酯化之磷酸雙澱粉；磷酸化磷酸雙澱粉、乙醯化磷酸雙澱粉、經乙酸酐酯化之乙酸澱粉、經乙酸乙烯酯酯化之乙酸澱粉、乙醯化己二酸雙澱粉、乙醯化雙澱粉甘油、辛烯基丁二酸澱粉鈉及/或其組合。羥丙基澱粉、羥丙基磷酸雙澱粉、羥丙基雙澱粉甘油亦可為適合的。經改質之酯化澱粉可進一步以鹽形式使用，諸如鈉鹽。
更佳地，使用第一及第二改質澱粉材料之組合，其中例如第一改質澱粉材料之分子量高於第二澱粉材料。已在此獲得良好實驗結果。最適合地，兩種改質澱粉材料均為所謂的冷水溶性澱粉。以實驗方式發現第二澱粉材料可在顆粒形成中添加，至少80 wt%、較佳地至少90 wt%該顆粒之尺寸在100-600 µm範圍內，且尤其減小小於100 µm之顆粒之量。較佳組合為酯化澱粉與糊精或麥芽糊精之組合。酯化澱粉更佳為鹽。最佳組合為辛烯基丁二酸澱粉鈉與糊精之組合。較佳認為第一改質澱粉之質量比以50 wt%至75 wt%之量存在且第二改質澱粉以25 wt%至50 wt%之量存在。更佳地，第一及第二改質澱粉之相互重量比介於1.5與2.5之間，諸如為1.8-2.2。
澱粉材料可具有任何所需來源，包括例如小麥澱粉、玉蜀黍澱粉、玉米澱粉、馬鈴薯澱粉、木薯澱粉、樹薯澱粉。當使用第一及第二改質澱粉時，不需要兩者皆來源於相同澱粉源。
較佳地，矽化合物與穩定劑組合使用來抑制矽化合物之聚合。該抑制更詳言之為使得防止形成不可溶於水且不再可水解之矽聚合物。此類矽聚合物為生物不可用的，亦即其消耗並不允許身體吸收呈準備吸收之形式的矽，該形式的矽尤其為矽酸單體正矽酸、其寡聚物及其可能的某些變體，諸如矽烷醇及矽酸鹽。可藉由使用以下各者獲得穩定化：胺基酸、諸如水楊酸、山梨糖醇酸、抗壞血酸、乳酸及己酸之其他有機酸、肽、肉鹼、諸如香草醛(4-羥基-3-甲氧基苯甲醛)之酚或多酚化合物、諸如甜菜鹼及膽鹼及其衍生物之四級銨化合物。膽鹼化合物為較佳的，且係選自例如氯化膽鹼、酒石酸氫膽鹼、氫氧化膽鹼、檸檬酸二氫膽鹼、2-4-二氯苯氧基乙酸膽鹼(2,4 D膽鹼鹽)、乙酸膽鹼、碳酸膽鹼、檸檬酸膽鹼、酒石酸膽鹼、乳酸膽鹼、磷酸二丁膽鹼；O,O'-二乙基二硫代磷酸膽鹼、二氫磷酸膽鹼；磷酸膽鹼。
已發現用氯化膽鹼之良好結果。當穩定劑為諸如氯化膽鹼之四級銨化合物時，液體製劑之特徵在於不良味道及不合意的氣味，可將其描述為魚腥味及苦味且其對產品順應性具有負面影響。使用諸如微晶纖維素之載體以獲得固體粒化製劑或液體填充之多醣膠囊克服此問題。然而，此等固體劑量製劑均不可溶於水。使用本發明之固體調配物克服此缺點。
在一最佳實施例中，矽酸化合物為稱為正矽酸之矽酸單體及/或其寡聚物。此對應於式(I)中之值x=0。正矽酸之生物可用性正好已在複數個科學研究中經證實，該等研究亦已經European Food Safety Authority(EFSA)承認。此外，與不存在於自然界中而係人造合成化合物之單甲基三矽醇相比，其為天然成分。
較佳地，在本發明中，矽酸實質上包含矽酸之寡聚物及/或單體。寡聚物為例如每分子包含小於1000個單體、較佳小於100個單體之寡聚物。更佳地，寡聚物為：至少80%及較佳至少90%之矽原子在本文中經矽-氧-矽橋鍵結合至至多3個其他矽原子。術語「實質上」在本文中適合地係指至少95wt%、較佳至少98wt%、更佳至少99wt%。僅聚合至在胃-腸道中可水解成單體、二聚體及三聚體之程度的矽酸製劑稱為生物可用矽。此類製劑之矽酸可由人體吸收。
在一替代實施例中，使用三矽醇化合物作為矽化合物，諸如單甲基三矽醇。此對應於式I中之x=1之選項。三矽醇化合物可進一步用於根據式(I)的矽化合物之摻合物中，其中x=0-2且較佳x=0、1。一個較佳側基Y為C1
-C4
烷基，諸如甲基。
作為另一偏好，固體調配物為微粒，其中藉助於篩析所量測，至少80 wt%之粒子之尺寸在100-800 µm範圍內。較佳實施例之篩析指示達到90%之顆粒小於600 µm之分佈的可行性。視情況，可應用篩分去選擇一部分具有特定、較窄粒度分佈之顆粒或去移除尺寸＞600 µm之粒子。更佳地，粒度分佈為小於100 µm之粒子部分占粒子之至多15 wt%、更佳地占粒子之至多10 wt%或甚至占粒子之至多5 wt%。
在另一實施例中，乾燥顆粒之矽濃度在0.002 wt%至2.0 wt%之範圍內。較佳地，矽濃度為至少0.01 wt%及更佳為至少0.1 wt%，以便限制顆粒體積達到自臨床研究已知之日劑量。最佳地，矽濃度高於0.5% w/w。後者可藉由組合矽化合物與諸如膽鹼化合物之穩定劑來達成。在一有利實施例中，顆粒中至少0.5% w/w之高矽濃度藉由使用正矽酸及/或其寡聚物作為矽化合物來達成。
在一較佳實施例中，將所產生之顆粒在其形成至預定義濕度之後乾燥。例如，此類濕度至多為5 wt%，儘管可替代地選擇至多4 wt%或至多3 wt%之水分含量。
根據一重要實施例，顆粒為流化顆粒。更詳言之，其可藉由包含以下步驟之方法獲得(1)提供該矽化合物之液體調配物；(2)將包含澱粉材料之微粒載體引入流化床造粒機中，及(3)在其操作期間將該液體調配物噴霧至流化床造粒機中，其中載體粒子經充當黏合劑之液體調配物聚結為顆粒。流化床造粒製程確保液體矽調配物貫穿載體材料之均勻分佈。此外，已發現良好的尺寸分佈，且流化製程產生具有相對較低密度及孔隙度之顆粒，其經認為對於溶解為有利的(包括膠態溶液之產生，其形式上為稀-懸浮液)。此實施例在以下組合中尤其重要：使用正矽酸及/或寡聚物作為矽化合物及存在用於矽化合物之穩定劑，及更詳言之膽鹼化合物作為穩定劑。已證明對於此特定矽化合物及其穩定劑，更難以用其他濕式造粒方法產生具有均勻顆粒尺寸之顆粒。
在一較佳實施例中，本發明之顆粒之密度在0.25-0.60 g/cm3
、更佳地0.30-0.55 g/mol，諸如0.33-0.36 g/cm3
或0.40-0.53 g/mol範圍內。此密度明顯地低於經擠塑-滾圓獲得的密度，因為此擠塑-滾圓典型地產生高於0.75 g/cm3
的密度。
在一較佳實施方案中，乾燥步驟發生在流化床造粒機中，顆粒在其中產生。噴霧、造粒及乾燥之3個不同步驟可藉由流化床造粒法進行，且在一個實施方案中在單個造粒機單元中進行。此類流化床造粒單元本身已知，例如來自Glatt，其具有用於不同製程步驟之多種附件。流化床造粒單元通常包含可關於位置及噴霧速率進行調節之噴霧嘴。較佳地，使用所謂的頂部噴嘴。適合噴霧速率在500-2000 g/min範圍內。
在另一實施例中，所獲得之顆粒可具備塗層，其較佳藉由流化床造粒法塗覆。若有此需要，則可將此類塗層在單個單元中在相同流化床造粒製程中塗覆。可進行塗層以改變風味或香味從而保護免受氧化、改變視覺外觀或用於腸溶塗層。塗層之實例為薄膜塗層、腸溶塗層、延遲釋放塗層、熱熔塗層。
在又另一實施例中，流化床造粒法用運載氣體，較佳空氣進行，將該運載氣體加熱至超過室溫。運載氣體之較佳溫度為至少50℃至多120℃，且較佳在70℃至100℃範圍內。經加熱之運載氣體進一步導致材料之乾燥。在一較佳實施例中，將25-40 wt%穩定矽酸噴霧至60-75 wt%載體材料，諸如改質澱粉，例如酯化澱粉。可將數種類型之改質澱粉組合以改變所得顆粒之粒度分佈。液態穩定矽酸調配物與載體材料之間的較佳比率為1:2。
在另一實施例中，將顆粒給藥且混合於飲料及液體食品中。因此，在一實施例中，將本發明之顆粒與營養物、基於植物之提取物、蛋白質及多種生物活性分子中之至少一者摻合且隨後封裝。此類摻合物亦已知在「Superfood」之名下。較佳地，使用具有粒度分佈如下之顆粒：至少90 wt%及較佳至少95 wt%或甚至100%之粒子之直徑為至多600 µm。此類特定粒度分佈使得有可能獲得完美摻合。不存在大粒子(＞600 µm)使得將摻合物組分之分離風險減到最小。
在食用之前，消費者可藉由將摻合物及/或顆粒與水、乳製品(諸如牛奶之液體及諸如酸酪乳之半液體)、果汁、蛋白飲料或其他飲料混合來製備營養組合物。或者，顆粒可封裝於小袋或棒狀包裝(stick pack)或另一類型之單次劑量封裝中，將內容物與飲料及/或(半)液體食品混合且立即食用。單次劑量封裝促進消費者在其旅行時食用產品。在另一應用中，顆粒用作用於製造其他固體劑量草本形式之原材料，例如錠劑、咀嚼錠、發泡錠劑及硬明膠或植物膠囊。
在另一實施方案中，此類劑型或封裝中之任一者可包括其他習知添加劑及營養物，諸如甜味劑；調味劑；賦形劑，諸如防結塊劑；微量元素，諸如鎂、硼、鈣、硒、鋅中之至少一者；維生素，諸如維生素C、維生素D、維生素K中之至少一者。
出於完整性起見觀測到，以上提及之實施例中之任一者均被視為與根據本發明之態樣中之任一者相關。
實例
在所有實例中，除非另外表述，否則百分比係指重量百分比。實例 1
氯化膽鹼經無水鹽酸處理。向所形成之膽鹼溶液(SiCl4
比膽鹼之比率：1 mol/1比5 mol)中添加四氯化矽(IV)。在約-10℃至-30℃之溫度範圍內冷卻的同時，所得溶液藉由添加水(冰/冰水)水解。藉由添加氫氧化鈉來中和溶液且將溫度維持在0℃以下。最終pH在1-1.5之間。pH值可經pH分析儀量測，該pH分析儀可商購自Stratos，MS A405型，Knick，配備有具有Ag/AgCl2
參考系統及液態KCl電解質之Memosens pH電極。在藉由活性碳純化之後，沈澱物係藉由過濾連同活性碳一起移除。藉由在真空下蒸餾降低水濃度直至獲得含有2.0-4體積%矽及60至80重量%氯化膽鹼及15至30重量%水的製劑為止。在蒸餾期間形成之沈澱藉由過濾移除。
將65,67%辛烯基丁二酸澱粉鈉(Emarusta A1, Matsutani Chemical Industry Co. Ltd., Japan)與1%磷酸三鈣之混合物添加至Flow塗佈機FLO-120(Freund Bldg, Japan)流化床系統中。藉由將入口空氣之溫度設為85℃且在產物已達到50℃之溫度時在改質澱粉上噴霧33,33%液體經膽鹼穩定之矽酸來開始流化床造粒製程。在噴霧之後，在50℃之產物溫度下在FLO-120單元中自動地開始乾燥流化顆粒，直至在顆粒中獲得小於3%之含水量。藉由篩析量測之粒度分佈之實例提供於表1中，說明96%之粒子具有小於595 µm(30網目)之尺寸。密度在0.408與0.525 g/ml之間。藉由石墨鍋爐原子吸收光譜法(GFAAS)量測，經乾燥之顆粒之元素矽濃度在0.75%與1.5%(w/w)之間。
表1：僅含有辛烯基丁二酸澱粉鈉作為載體之膽鹼穩定之矽酸顆粒的篩析。
| 網目 ( 微米 ) | 保留於篩上之粒子 % |
| 16 (1190) | 0 |
| 22 (761) | 1 |
| 30 (595) | 3 |
| 42 (380) | 10 |
| 60 (250) | 16 |
| 83 (187) | 25 |
| 100 (145) | 16 |
| 140 (105) | 24 |
| 200 (74) | 5 |
藉由石墨鍋爐原子吸收光譜法量測，經乾燥之顆粒之元素矽濃度在0.75%與1.5% (w/w)之間。出乎意料地，對含有500 mg顆粒於500 ml溶解介質中之溶解介質的分析顯示當使用GFAAS或鉬藍比色方法分析時之一致概況(參見圖1)。後者僅對單體矽酸具反應性。此表明造粒製程不會引起穩定矽酸之聚縮合，且其在水性環境中自澱粉載體快速釋放。
顆粒展示極佳穩定性，因為當在40℃及75%相對濕度下在密封容器中培育6個月時，藉由比色鉬藍方法量測之矽濃度不顯著變化(參見表2)。
表2：在40℃及75 RH下在密封容器中培育之經膽鹼穩定之矽酸顆粒的穩定性。實例 2
| 在 40 ℃ / 75 % 相對濕度下之培育時間 | 用比色鉬藍方法量測之矽濃度 %( w / w ) |
| 0個月 | 1.03 |
| 1個月 | 1.07 |
| 2個月 | 1.07 |
| 3個月 | 1.04 |
| 4個月 | 1.09 |
| 5個月 | 1.09 |
| 6個月 | 1.05 |
使用以下配方將根據實例1製備之矽酸顆粒與甜味劑、鹽及調味劑混合：
| 成分 | 量 |
| 麥芽糖醇 | 64% |
| 穩定矽酸顆粒 | 25% |
| 氯化鈉 | 0.50% |
| 檸檬酸 | 5.25% |
| 葡萄柚調味劑 | 3.5% |
| 檸檬調味劑 | 1% |
| 以下之混合物：24%蔗糖素、18%乙醯磺胺酸K | 0.75% |
摻合物具有極佳流動特性且可容易地封裝於單劑量棒封裝中(每個棒封裝4 g)。在6個月期間在40℃下培育經填充之棒封裝以測試調味顆粒之穩定性。如表3中所示，發現極佳穩定性且在穩定矽酸與所添加之化合物之間不發生相互作用。
表3：在40℃及75 RH下在棒封裝中培育之經膽鹼穩定之矽酸顆粒與甜味劑及調味劑之摻合物的穩定性。實例 3
| 在 40 ℃ / 75 % 相對濕度下之培育時間 | 根據 GFAAS 之 矽濃度 % ( w / w ) | 根據鉬藍方法之矽濃度 % ( w / w ) |
| 0個月 | 0.27 | 0.27 |
| 1個月 | 0.25 | 0.24 |
| 3個月 | 0.26 | 0.26 |
| 6個月 | 0.26 | 0.25 |
氯化膽鹼經無水鹽酸處理。向所形成之膽鹼溶液(SiCl4
與膽鹼之比率：1 mol/1比5 mol)中添加四氯化矽(IV)。在約-10℃至-30℃之溫度範圍內冷卻的同時，所得溶液藉由添加水(冰/冰水)水解。藉由添加氫氧化鈉來中和溶液且將溫度維持在0℃以下。最終pH在1-1.5之間。pH值可經pH分析儀量測，該pH分析儀可商購自Stratos，MS A405型，Knick，配備有具有Ag/AgCl2
參考系統及液體KCl電解質之Memosens pH電極。在藉由活性碳純化之後，藉由過濾連同活性碳一起移除沈澱物。藉由在真空下蒸餾降低水濃度直至獲得含有2.0-4體積%矽及60至80重量%氯化膽鹼及15至30重量%水的製劑為止。在蒸餾期間形成之沈澱藉由過濾移除。
改質澱粉，亦即可商購自Capsul HS(Ingredion)之辛基丁二酸澱粉及糊精(Crystal Tex 626, Ingredion)，及其組合，可用作實驗室規模流化床裝置類型GPCG 1.1(Glatt)中之液體經膽鹼穩定之矽酸(ch-OSA)的載體。配方在表4中給出。乾燥澱粉及糊精用80℃至100℃之熱入口空氣流流化，產生在60℃-70℃範圍內之最大產物溫度。將經膽鹼穩定之矽酸經頂部噴嘴噴霧於載體上，導致顆粒之形成，該等顆粒在相同裝置中乾燥直至獲得小於3.5%之乾燥失重為止。視配方而定，乾燥顆粒之密度在330與360 g/l之間。篩析展示超過90%之粒子小於600 µm(參見表5)。糊精之使用產生較少灰塵(亦即低於100 µm之粒子)，其改良所得顆粒之可加工性及流動性。
表4：在流化床裝置類型GPCG 1.1(Glatt)中製造之製劑的配方。
表5：在流化床裝置類型GPCG 1.1(Glatt)中製造之製劑的篩析。實例 4
| 製劑 | ch-OSA (g) | Capsul HS (g) | Crystal tex 626 (g) |
| A47-01 | 500 | 1000 | - |
| A47-03 | 750 | 1500 | - |
| A47-04 | 750 | 1000 | 500 |
| 粒度 | A47-01 | A47-03 | A47-04 |
| % ＞ 800 µm | 0 | 0 | 2 |
| % 600-800 µm | 0 | 0 | 2 |
| % 400-600 µm | 4 | 0 | 6 |
| % 200-400 µm | 14 | 18 | 56 |
| % 100-200 µm | 48 | 70 | 34 |
| ＜ 100 µm | 34 | 12 | 0 |
使用8 kg Capsul HS及4 kg Crystal Tex 626之混合物，但使用僅65℃之入口空氣流重複實例3，該混合物用作較大中試規模GPCG15系統(Glatt)中6 kg經膽鹼穩定之矽酸的載體，該入口空氣流產生53℃之最大產物溫度。同樣，在此等條件下，中試規模之流化床製程產生具有超過90%之粒子之尺寸小於600 µm的顆粒(參見表6)。由於在500-2000 g/mol範圍內在實驗A47-06中使用比在實驗A47-05中更高之噴霧速率，顆粒變得更粗糙，且消除極細粒子(粉塵，＜100 µm)。
表6：在中試規模流化床裝置類型GPCG 15(Glatt)中製造之製劑的篩析。
| 粒度 | A47-05 | A47-06 |
| % ＞ 800 µm | 1 | 3 |
| % 600-800 µm | 1 | 4 |
| % 400-600 µm | 5 | 16 |
| % 200-400 µm | 48 | 49 |
| % 100-200 µm | 42 | 28 |
| ＜ 100 µm | 3 | 0 |
用於實驗室規模與中試規模兩者之所有製劑之矽濃度在0.99與1.05% (w/w)之間。製劑之水含量在2與3% (w/w)之間。實例 5
在工業層級上重複實例4：在配備有頂部噴霧噴嘴之GPCG 300流化床系統中，140.8 kg Capsul HS及70.4 kg Crystal Tex 626用作105.6 kg經膽鹼穩定之矽酸的載體。使用65℃之入口空氣溫度將固體材料加熱至53℃，隨後以540-1800 g/min之噴霧速率及2巴壓力將經膽鹼穩定之矽酸噴霧至流化床中。為了乾燥，使用類似入口空氣溫度，產生最終顆粒之3-4%之水分含量。
所得顆粒之容積密度為0.356 g/cm3
且93%之顆粒之尺寸低於600 µm，且94%之顆粒之尺寸為至少125 µm。粒度分佈展示於表7中，其表明工業規模之實驗中所獲得之粒度分佈與實驗室規模實驗無顯著不同。該製程之總輸出為293 kg顆粒。
隨機取樣以檢查均質性。概述於表8中之結果展現均質產物之形成。此證實工業造粒製程不會導致穩定矽酸之聚縮合，因為GFAAS及鉬分析揭示矽濃度無差異。
表7：在工業層級上用流化床裝置類型GPCG 300(Glatt)製造之顆粒的篩析。
表8：在流化床裝置類型GPCG 300(Glatt)中製造之顆粒之隨機選擇樣本的化學分析。實例 6
| 粒度 | 批次 18G26 |
| % ＞ 1180 µm | 0.61 |
| % 600-1180 µm | 6.3 |
| % 400-600 µm | 18.1 |
| % 200-400 µm | 62.3 |
| % 125-200 µm | 7.1 |
| ＜ 125 µm | 5.5 |
| 樣本 批次 18G26 | 根據GFAAS 之矽濃度 % ( w / w ) | 根據鉬藍方法之矽濃度 % ( w / w ) | 氯化膽鹼 % ( w / w ) | 水分 % (w /w ) |
| 1 | 1.06 | 0.96 | 25.0 | 3.54 |
| 2 | 0.99 | 1.00 | 24.9 | 3.81 |
| 3 | 1.00 | 0.99 | 25.2 | 3.92 |
使用以下配方將實例1中所獲得之顆粒壓縮成錠劑：
- 200 mg經膽鹼穩定之矽酸顆粒
- 90.01 mg微晶纖維素
- 6 mg硬脂酸鈣
- 3.99 mg磷酸三鈣
- 3 mg蟲膠
發現錠劑當封裝於鋁/鋁(alu/alu)箔中及在40℃及75%相對濕度下培育3個月時為穩定的，因為GFAAS及鉬分析揭示矽濃度無差異且崩解時間隨時間保持類似(表9)。
表9：封裝在密封鋁/鋁袋中及在40℃及75%相對濕度下培育之錠劑之穩定性。實例 7
| 基線 | 1 個月 | 3 個月 | |
| 根據GFAAS 之矽濃度 毫克 / 錠劑 | 2.06 | 2.03 | 1.94 |
| 根據鉬藍方法之矽濃度 毫克 / 錠劑 | 1.90 | 1.95 | 1.94 |
| 崩解時間 | 47'30'' | 52'30'' | 48'55'' |
使用以下配方將實例1中所獲得之顆粒壓縮成咀嚼錠劑：
- 500 mg經膽鹼穩定之矽酸顆粒
- 1.25 g微晶纖維素
- 650 mg 阿得凡糖(advantose)
- 10 mg蔗糖素
- 300 mg麥芽糊精
- 100 mg硬脂酸鎂
- 30 mg薑-檸檬調味劑
- 30 mg香蕉調味劑
- 45 mg抗壞血酸
發現錠劑當封裝於鋁/鋁箔中及在40℃及75%相對濕度下培育3個月時為穩定的，因為GFAAS及鉬分析揭示矽濃度無差異，其亦隨時間保持不變(表10)。
表10：封裝於密封鋁/鋁袋中及在40℃及75%相對濕度下培育之咀嚼錠的穩定性。
| 基線 | 1 個月 | 3 個月 | |
| 根據GFAAS 之矽濃度 毫克 / 錠劑 | 5.05 | 4.99 | 5.00 |
| 根據鉬藍方法之矽濃度 毫克 / 錠劑 | 4.98 | 4.89 | 4.90 |
| 崩解時間 | 47'30'' | 52'30'' | 48'55'' |
參考實例及圖式進一步闡明本發明之此等及其他態樣，其中
圖1A展示藉由GFAAS量測之溶解介質之矽濃度(元素矽)。在溶解裝置中，使用500 ml溶解介質，在37℃及1000 rpm混合速度下培育500 mg穩定矽酸顆粒(批次I-160713)。240分鐘後之矽濃度為1.01% (GFAAS) w/v；
圖1B展示藉由比色鉬藍方法量測之溶解介質的矽濃度(專門針對單體矽酸)。在溶解裝置中，使用500 ml溶解介質，在37℃及1000 rpm混合速度下培育500 mg穩定矽酸顆粒(批次I-160713)。240分鐘後之矽濃度為0.95%(比色法)w/v。
Claims (18)
- 一種水溶性含矽顆粒，其包含 式Yx Si(OH)4 - x 之矽化合物或其寡聚物，其中Y為視情況經取代之(C1 -C4 )烷基、(C2 -C5 )烯基、(C1 -C4 )烷氧基、胺基且其中x為0-2，及 冷水溶性澱粉材料。
- 如請求項1之水溶性顆粒，其進一步包含抑制該矽化合物之聚合之穩定劑。
- 如請求項2之水溶性顆粒，其中該穩定劑係選自以下之群：胺基酸、肽、有機酸、酚及多酚化合物、諸如麥芽糖糊精之多元醇、四級銨化合物及醛，較佳地其中該穩定劑為或包含諸如膽鹼之四級銨化合物。
- 如請求項1至3之水溶性顆粒，其中該矽化合物係選自以下之群：正矽酸或其寡聚物(式中x=0)，及單(C1 -C4 )烷基三矽醇及其組合，且較佳地，該矽化合物為正矽酸或其寡聚物。
- 如前述請求項中任一項之水溶性顆粒，其中該顆粒為流化顆粒，其可獲自流化床造粒法。
- 如前述請求項中任一項之水溶性顆粒，其中該顆粒之密度在0.30-0.60 g/cm3 範圍內。
- 如前述請求項中任一項之水溶性顆粒，其中至少90 wt%及較佳至少95 wt%之該等顆粒之直徑為至多600 µm，且較佳地至少80 wt%、更佳地至少90 wt%之該等顆粒之直徑為至少100 µm。
- 如前述請求項中任一項之水溶性顆粒，其中該冷水溶性澱粉材料包含已經化學改質之澱粉。
- 如請求項8之水溶性顆粒，其中該澱粉已經有機酸化學改質成酯化澱粉或其鹽，例如改質成辛基丁二酸澱粉或其鹼金屬鹽。
- 如前述請求項中任一項、較佳地如請求項9之水溶性顆粒，其中該冷水溶性澱粉材料包含糊精或麥芽糖糊精。
- 如前述請求項中任一項之水溶性顆粒，其中以該顆粒之總重量計，矽濃度在0.5-2.0 wt%範圍內。
- 一種製備水溶性含矽顆粒之方法，其包含以下步驟： 提供式Yx Si(OH)4 - x 之矽化合物或其寡聚物之液體調配物，其中Y為視情況經取代之(C1 -C4 )烷基、(C2 -C5 )烯基、(C1 -C4 )烷氧基、胺基，且其中x為0-2，且較佳地x=0； 提供冷水溶性澱粉材料，及 混合該液體調配物及該冷水溶性澱粉材料，使得該矽化合物吸附於該澱粉材料上且形成含矽顆粒。
- 如請求項12之方法，其中該液體調配物進一步包含抑制該矽化合物之聚合之穩定劑，該穩定劑較佳係選自以下之群：胺基酸、肽、有機酸、酚及多酚化合物、諸如麥芽糖糊精之多元醇、四級銨化合物及醛，更佳地，其中該穩定劑為或包含諸如膽鹼之四級銨化合物。
- 如請求項12或13之方法，其中該澱粉材料經提供至流化床造粒機中待流化，且其中該液體調配物在其操作期間經噴霧至該流化床造粒機中，其中澱粉材料粒子經充當黏合劑之液體調配物聚結為顆粒。
- 一種顆粒，其可藉由如請求項12至14中任一項之方法獲得。
- 一種草本(galenic)或營養組合物，諸如封裝或劑型，其包含如前述請求項1至11及15中任一項之顆粒。
- 一種如請求項16之營養組合物之用途，其在經水、飲料及/或其他水溶液或分散液溶解及/或分散之後作為食品補充物或飼料補充物。
- 如請求項16之草本組合物，其適用於預防、抑制及/或治療骨質流失及軟骨退化相關疾病、毛髮指甲品質喪失、禿髮及皮膚老化疾病。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18205367.8 | 2018-11-09 | ||
| EP18205367.8A EP3650011A1 (en) | 2018-11-09 | 2018-11-09 | Water soluble silicon-containing granulate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202028330A true TW202028330A (zh) | 2020-08-01 |
Family
ID=64270683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW108140859A TW202028330A (zh) | 2018-11-09 | 2019-11-11 | 水溶性含矽顆粒 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20210393528A1 (zh) |
| EP (1) | EP3650011A1 (zh) |
| JP (1) | JP2022507031A (zh) |
| KR (1) | KR20210091229A (zh) |
| CN (1) | CN113271927A (zh) |
| AR (1) | AR120972A1 (zh) |
| AU (1) | AU2019377241A1 (zh) |
| BR (1) | BR112021009002A2 (zh) |
| CA (1) | CA3119225A1 (zh) |
| EA (1) | EA202191324A1 (zh) |
| IL (1) | IL282918A (zh) |
| TW (1) | TW202028330A (zh) |
| WO (1) | WO2020094886A1 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3632449A1 (en) | 2018-10-05 | 2020-04-08 | Bio Minerals N.V. | Silicic acids for use in the treatment of periodontitis |
| IT202200009089A1 (it) | 2022-05-04 | 2023-11-04 | Geofarma S R L | Composizione a base di silicio biodisponibile e vitamine |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3515591A (en) * | 1967-04-10 | 1970-06-02 | Gen Foods Corp | Cold water-dispersible starch composition and method for making same |
| NL9400189A (nl) | 1994-02-07 | 1995-09-01 | Bio Pharma Sciences Bv | Gestabiliseerd orthosiliciumzuur bevattend preparaat, een werkwijze voor het bereiden daarvan en een biologisch preparaat. |
| EP1391426A1 (en) | 2002-08-12 | 2004-02-25 | Bio Minerals N.V. | Method for the preparation of a silicic acid comprising extrudate, said extrudate, its use and a pharmaceutical composition comprising the said extrudate |
| CN101279737A (zh) * | 2008-05-29 | 2008-10-08 | 嘉兴市红日化工有限公司 | 一种原硅酸的制备方法 |
-
2018
- 2018-11-09 EP EP18205367.8A patent/EP3650011A1/en active Pending
-
2019
- 2019-11-11 KR KR1020217017663A patent/KR20210091229A/ko unknown
- 2019-11-11 AU AU2019377241A patent/AU2019377241A1/en active Pending
- 2019-11-11 AR ARP190103303A patent/AR120972A1/es unknown
- 2019-11-11 CN CN201980088688.4A patent/CN113271927A/zh active Pending
- 2019-11-11 BR BR112021009002-9A patent/BR112021009002A2/pt unknown
- 2019-11-11 EA EA202191324A patent/EA202191324A1/ru unknown
- 2019-11-11 JP JP2021524433A patent/JP2022507031A/ja active Pending
- 2019-11-11 CA CA3119225A patent/CA3119225A1/en active Pending
- 2019-11-11 WO PCT/EP2019/080894 patent/WO2020094886A1/en active Application Filing
- 2019-11-11 TW TW108140859A patent/TW202028330A/zh unknown
- 2019-11-19 US US17/292,151 patent/US20210393528A1/en active Pending
-
2021
- 2021-05-04 IL IL282918A patent/IL282918A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2019377241A1 (en) | 2021-05-27 |
| IL282918A (en) | 2021-06-30 |
| EP3650011A1 (en) | 2020-05-13 |
| WO2020094886A1 (en) | 2020-05-14 |
| AR120972A1 (es) | 2022-04-06 |
| EA202191324A1 (ru) | 2021-08-05 |
| CA3119225A1 (en) | 2020-05-14 |
| JP2022507031A (ja) | 2022-01-18 |
| KR20210091229A (ko) | 2021-07-21 |
| US20210393528A1 (en) | 2021-12-23 |
| BR112021009002A2 (pt) | 2021-08-10 |
| CN113271927A (zh) | 2021-08-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2463947C (en) | Montelukast granule formulation | |
| JP5322643B2 (ja) | カプセル化された活性成分、カプセル化された活性成分の製造方法および使用 | |
| JP6239579B2 (ja) | カルニチン顆粒およびその製造方法 | |
| JP2010265309A (ja) | ケイ酸含有押出物の製造方法、前記押出物、その使用、及び前記押出物を含む医薬組成物 | |
| AU2002333134A1 (en) | Montelukast granule formulation | |
| TW202028330A (zh) | 水溶性含矽顆粒 | |
| AU2008241690A1 (en) | High dose composition of ursodeoxycholic acid | |
| JP6930537B2 (ja) | ビタミン製剤 | |
| JP4820288B2 (ja) | 食物繊維を含有する健康食品の製造方法 | |
| CN106619565B (zh) | 精氨酸制剂及其制备方法和应用 | |
| JP5697080B2 (ja) | 粉末組成物 | |
| TW201722293A (zh) | 含有膠原蛋白胜肽與神經醯胺之組成物及其製造方法 | |
| EA046362B1 (ru) | Водорастворимый кремнийсодержащий гранулят | |
| CN114128763B (zh) | 一种维生素d3营养强化剂及其制备方法和应用 | |
| JP6267862B2 (ja) | ゼリー化組成物 | |
| JP6004702B2 (ja) | 不快味が軽減された固形製剤の製造方法 | |
| JP4178361B2 (ja) | キトサン含有粉体 | |
| JP2002255793A (ja) | 粒状製剤 | |
| JP2008260783A (ja) | キトサン含有粉体 | |
| JPH11506473A (ja) | 湿式粒状化方法 | |
| KR20150070501A (ko) | 함습성이 개선된 복합 아미노산 조미료 조성물 |