CN105560211B - 优化包埋的微囊制剂 - Google Patents
优化包埋的微囊制剂 Download PDFInfo
- Publication number
- CN105560211B CN105560211B CN201511019154.6A CN201511019154A CN105560211B CN 105560211 B CN105560211 B CN 105560211B CN 201511019154 A CN201511019154 A CN 201511019154A CN 105560211 B CN105560211 B CN 105560211B
- Authority
- CN
- China
- Prior art keywords
- glyceride
- microcapsule formulation
- fatty acid
- fatty
- wall material
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 48
- 239000003094 microcapsule Substances 0.000 title claims abstract description 45
- 238000009472 formulation Methods 0.000 title claims abstract description 30
- 239000000463 material Substances 0.000 claims abstract description 45
- 239000000194 fatty acid Substances 0.000 claims abstract description 33
- 125000005456 glyceride group Chemical group 0.000 claims abstract description 27
- 239000011162 core material Substances 0.000 claims abstract description 22
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 18
- 229930195729 fatty acid Natural products 0.000 claims abstract description 18
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 11
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 26
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 16
- 235000019482 Palm oil Nutrition 0.000 claims description 16
- 239000002540 palm oil Substances 0.000 claims description 16
- 229940000635 beta-alanine Drugs 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 11
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical group CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 8
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims description 4
- QHZLMUACJMDIAE-UHFFFAOYSA-N 1-monopalmitoylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)CO QHZLMUACJMDIAE-UHFFFAOYSA-N 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- 235000019156 vitamin B Nutrition 0.000 claims description 2
- 239000011720 vitamin B Substances 0.000 claims description 2
- 229940046001 vitamin b complex Drugs 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 238000005457 optimization Methods 0.000 abstract description 8
- 229910052799 carbon Inorganic materials 0.000 abstract description 6
- 150000004665 fatty acids Chemical class 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 2
- 239000011149 active material Substances 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 238000000034 method Methods 0.000 description 21
- 239000000047 product Substances 0.000 description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 239000008363 phosphate buffer Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 9
- 239000004519 grease Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000003578 releasing effect Effects 0.000 description 8
- 239000007921 spray Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000002245 particle Substances 0.000 description 7
- -1 wet granulation Substances 0.000 description 7
- 235000009508 confectionery Nutrition 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 5
- 229930064664 L-arginine Natural products 0.000 description 5
- 235000014852 L-arginine Nutrition 0.000 description 5
- 235000010323 ascorbic acid Nutrition 0.000 description 5
- 239000011668 ascorbic acid Substances 0.000 description 5
- 229960005070 ascorbic acid Drugs 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 244000068988 Glycine max Species 0.000 description 4
- 235000010469 Glycine max Nutrition 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 4
- 238000000889 atomisation Methods 0.000 description 4
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 239000010513 hydrogenated corn oil Substances 0.000 description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
- 239000008117 stearic acid Substances 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 235000019486 Sunflower oil Nutrition 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002600 sunflower oil Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- UOQDKQOXSLQEOJ-UHFFFAOYSA-N 2-methylprop-2-enoate;trimethylazanium Chemical compound C[NH+](C)C.CC(=C)C([O-])=O UOQDKQOXSLQEOJ-UHFFFAOYSA-N 0.000 description 2
- 235000003276 Apios tuberosa Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- 235000010777 Arachis hypogaea Nutrition 0.000 description 2
- 235000010744 Arachis villosulicarpa Nutrition 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930003537 Vitamin B3 Natural products 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000005243 fluidization Methods 0.000 description 2
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- RZJRJXONCZWCBN-UHFFFAOYSA-N octadecane Chemical compound CCCCCCCCCCCCCCCCCC RZJRJXONCZWCBN-UHFFFAOYSA-N 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 235000021081 unsaturated fats Nutrition 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000019160 vitamin B3 Nutrition 0.000 description 2
- 239000011708 vitamin B3 Substances 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- ADHNUPOJJCKWRT-JLXBFWJWSA-N (2e,4e)-octadeca-2,4-dienoic acid Chemical compound CCCCCCCCCCCCC\C=C\C=C\C(O)=O ADHNUPOJJCKWRT-JLXBFWJWSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- ARIWANIATODDMH-AWEZNQCLSA-N 1-lauroyl-sn-glycerol Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)CO ARIWANIATODDMH-AWEZNQCLSA-N 0.000 description 1
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 1
- MUZDXNQOSGWMJJ-UHFFFAOYSA-N 2-methylprop-2-enoic acid;prop-2-enoic acid Chemical compound OC(=O)C=C.CC(=C)C(O)=O MUZDXNQOSGWMJJ-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 102000004407 Lactalbumin Human genes 0.000 description 1
- 108090000942 Lactalbumin Proteins 0.000 description 1
- ARIWANIATODDMH-UHFFFAOYSA-N Lauric acid monoglyceride Natural products CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 101710089165 Protein white Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 239000004990 Smectic liquid crystal Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 235000001667 Vitex agnus castus Nutrition 0.000 description 1
- 244000063464 Vitex agnus-castus Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 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
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LUJQXGBDWAGQHS-UHFFFAOYSA-N ethenyl acetate;phthalic acid Chemical compound CC(=O)OC=C.OC(=O)C1=CC=CC=C1C(O)=O LUJQXGBDWAGQHS-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005428 food component Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 229940038384 octadecane Drugs 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 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
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000010148 water-pollination Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
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
- A61K9/48—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
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- General Preparation And Processing Of Foods (AREA)
Abstract
本发明提供一种优化包埋的微囊制剂,以壁材和壁材助剂的混合物作为释放材料,所述的壁材助剂包括脂肪酸基碳原子数为12~22的饱和或不饱和脂肪酸甘油酯,所述的脂肪酸甘油酯是单脂肪酸甘油酯、双脂肪酸甘油酯或二者按照任意比例的混合物。本发明在微囊制剂中使用脂肪酸甘油酯,具有优良的促进包埋效果,可有效降低表面芯材含量,优化活性物质的释放行为。
Description
技术领域
本发明属于微囊化技术领域,尤其涉及性能优化的微囊产品。
背景技术
通过微囊技术制成的缓释粉末、微粒、微囊等,产品除可获得稳定、防潮、掩味、控释的特性,在粒径上与原料几乎一致,可以制成固体饮料,或直接将其添加到液体中,使其更利于吸收和食用。另外,也可灵活地制成片剂或胶囊。通常缓释制剂较普通制剂药物服用量小,对于多数药物来说制成缓释片剂服用较容易,但对于一些服用剂量大的营养物质,如氨基酸、植物提取物等,较大的片剂和较多的服用剂量降低了依从性,人们更愿意将其制成可以冲服或可制成悬浮液的粉剂或颗粒剂。
微囊化的方法有很多,常用的方法包括流化包衣、湿法制粒、喷雾冷凝等。流化包衣是将芯材颗粒悬浮于高速气流中,将有缓控释作用的包衣液雾化包覆到悬浮颗粒表面,通过干燥或固化,在颗粒表面形成一定组成和厚度的衣膜。湿法制粒是将芯材颗粒与包衣液在高速搅拌条件下混合,然后再烘干除去溶剂或冷却固化的方法。喷雾冷凝是将芯材溶解或分散至熔化的脂肪中,经雾化形成小液滴落入冷却室中,脂肪凝固形成细小颗粒。所述的几种制剂方法各有千秋,需要根据制剂体系来选择最适合的方法。
除此以外,微囊化材料也是决定微囊制剂优劣的重要因素。可用于微囊化制剂生产的壁材可以归纳为以下:天然产物及其简单提取物如巴西棕榈蜡、鲸蜡、玉米胶、琼脂、海藻酸钠、明胶、虫胶、果胶、爪耳树胶、角叉菜胶、刺槐豆胶、西黄蓍胶和胆甾醇、大豆分离蛋白、酪蛋白、乳清蛋白。纤维素衍生物有乙基纤维素、甲基纤维素、邻苯二甲酸羟丙基甲基纤维素、邻苯二甲酸醋酸纤维素、羟乙基纤维素、羟乙基甲基纤维素、羟丙基纤维素、羟丙基甲基纤维素、羟甲基纤维素和羟甲基纤维素钠。丙烯酸树脂有甲基丙烯酸二甲氨基乙酯-中性甲基丙烯酸酯共聚物、丙烯酸乙酯-甲基丙烯酸甲酯共聚物、甲基丙烯酸-丙烯酸甲酯共聚物、甲基丙烯酸三甲铵酯-丙烯酸酯共聚物、甲基丙烯酸三甲铵酯-甲基丙烯酸酯共聚物和丙烯酸-甲基丙烯酸酯。乙烯基聚合物有聚邻苯二甲酸乙酸乙烯酯、聚乙烯吡咯烷酮、聚乙烯醇、聚苯乙烯、聚羟乙烯和聚氢乙烯。其他还有十八烷醇、甘油-硬脂酸酯、尼龙、壳多糖、氢化植物油、脱乙酰壳多糖、邻苯二甲酸二乙酯、邻苯二甲酸二辛酯、硬脂酸、葡萄糖、聚乙二醇、聚丙烯和聚硅氧烷。以上材料中,热熔性的脂肪及蜡质材料相对于以水或有机溶剂为介质的释放材料应用更为广泛安全,但仍然存在微囊表面覆盖壁材占比较低、表面芯材含量较高,图层重叠,不连续等诸多问题,导致出现芯材突然释放等严重产品问题。也因此,壁材的用量很高,而微囊化效率却非常低,生产成本居高不下。
单/双脂肪酸甘油酯的英文名为Monoglycerides(MG),根据主要组成脂肪酸组成,常用的该类甘油酯包括单/双硬脂酸甘油酯(Glycerol monostearate)、单/双月硅酸甘油酯(Glycerol monolaurate)、单/双油酸甘油酯(Glycerol monooleate)等,单/双脂肪酸甘油酯一般可为油状、脂状或蜡状,色泽为淡黄或象牙色,油脂味或无味,这与脂肪基团的大小及饱和程度有关,具有优良的感官特性。这类物质往往不溶于水和甘油,但能在水中形成稳定的水合分散体,其HLB值为2~3。通过改变组成单甘酯的脂肪酸碳链的长度和饱和性,可以调整其HLB值。与油脂相似,单、双甘油酯以多种晶型或变晶型存在。
单/双脂肪酸甘油酯分子中含甘油羟基及脂肪酸长碳链,分别具有亲水性和亲油性。这种两亲性的分子结构可使单、双甘油酯分子在油相和水相间的界面形成一层膜,降低液体的表面张力,具有很好的乳化性能,为优良的W/O乳化剂,HLB值为3~5。由于单/双脂肪酸甘油酯为非离子表面活性荆,在水中不电离,稳定性高,其表面活性不受电解质及酸碱的影响,与其他品种的表面活性剂兼容性好。单双甘油酯还可与淀粉、蛋白质等食物组分形成复台体,能抑制淀粉的老化,改善食品的性能,常用作优良的食品乳化剂。
发明内容
本发明的目的在于提供一种优化包埋的微囊制剂,以壁材和壁材助剂的混合物作为释放材料,所述的壁材助剂包括脂肪酸基碳原子数为12~22的饱和或不饱和脂肪酸甘油酯,所述的脂肪酸甘油酯是单脂肪酸甘油酯、双脂肪酸甘油酯或二者按照任意比例的混合物。
本发明采用具有缓释作用的材料与微囊化工艺相结合,获得缓释微囊化功能活性成分,采用微囊化工艺获得的产品为与原料粒径基本一致的微囊、颗粒或粉末,粒径为100~1000μm,其中活性成分重量百分含量为50~95%,经缓释微囊化后,口服相同剂量活性成分可降低或不产生异常感觉。
另一方面,现有技术中通常作为乳化剂使用的脂肪酸甘油酯,在本发明的应用体系中,能有效提高微囊包埋效率,降低表面芯材含量,提高产品稳定性,延长货架期。因此本发明另一方面也公开脂肪酸甘油酯,尤其是单/双脂肪酸甘油酯或其混合物在优化微囊包埋方面的应用。具体而言,是在促进包埋方面的应用。本发明所提供的优化包埋的微囊制剂亦即该应用所得的制剂,该产品具有更优秀的释放表现:微囊制剂颗粒表面壁材连续相溶,不发生、或少发生层叠,避免了层叠间隙的存在,实现对活性成分的有效包埋。通过实验也进一步证明,本发明的方法及产品,能有效控制微囊表面活性成分含量在极低水平,产品性能表现优异。在防止吸潮、掩盖芯材引起的不良气味方面有更加优异的表现。
具体实施方式
本发明源于对脂肪酸甘油酯,尤其是单/双脂肪酸甘油酯或其混合物在优化微囊包埋方面的新用途的认识。具体而言,是脂肪酸甘油酯在促进微囊包埋中的应用。
上述应用的结果,本发明得以提供一种性能更加优越的微囊制剂。所述微囊制剂,以壁材和壁材助剂的混合物作为释放材料,所述的壁材助剂含有脂肪酸基碳原子数为12~22的饱和或不饱和脂肪酸甘油酯,其中的脂肪酸甘油酯是单脂肪酸甘油酯、双脂肪酸甘油酯或二者按照任意比例的混合物。
本发的上述应用及微囊制剂的具体实施方式之一,其中所述的脂肪酸甘油酯中的脂肪酸基是碳原子数为16~18的饱和或不饱和脂肪酸基。优选十六烷酸基、十六碳一烯酸基、十八烷酸基、十八碳一烯酸基、十八碳二烯酸基或十八碳三烯酸基。更为优选地,所述的脂肪酸甘油酯选自单硬脂酸甘油酯、双硬脂酸甘油酯、单棕榈酸甘油酯、双棕榈酸甘油酯,及其中任意2种或2种以上的混合物。
另一具体的实施方式中,所述的脂肪酸甘油酯是单脂肪酸甘油酯与双脂肪酸甘油酯按照摩尔比1:0.2~1.5的混合物。优选1:0.5~1:1.0,更优选1:0.6~1:0.9。
再一具体的实施方式中,所述的释放材料中脂肪酸甘油酯的质量含量为0.2~5%。优选0.4~3%,更优选0.5~1%。
本发明的上述应用及微囊制剂中,另一具体的实施方式是:所述的壁材是氢化植物油。优选选自氢化棕榈油、氢化椰子油、氢化大豆油、氢化葵花油、氢化花生油、氢化棉籽油、氢化玉米油,以及其中2种或2种以上按照任意比例的混合物。最优选壁材是氢化棕榈油。在此基础上,进一步优选的实施方式是使所述的脂肪酸甘油酯和氢化棕榈油的质量比为1:20~500,优选1:50~250,更优选1:100~200。
本发明的应用及微囊制剂中,再一具体的实施方式是:所述的芯材选自氨基酸和维生素。优选选自β-丙氨酸、α-丙氨酸、精氨酸、左旋肉碱、维生素C和维生素B族。最优选芯材是β-丙氨酸。
本发明的应用或微囊制剂中,又一具体实施的方式中,所述的壁材选自氢化棕榈油、氢化椰子油、氢化大豆油、氢化葵花油、氢化花生油、氢化棉籽油、氢化玉米油,以及其中2种或2种以上按照任意比例的混合物;并且,所述芯材选自氨基酸和维生素。进一步优选的是所述壁材是氢化棕榈油,且所述芯材是β-丙氨酸。所述的芯材与释放材料的比例优选1:0.1~2.0。
本发明所述的优化包埋的微囊制剂可采用本领域技术人员所熟知的常规方法,这些方法可举例但不限于空气悬浮流化床包衣(Wurster)、喷雾干燥、高效湿法制粒等。以下述几种具体的微囊制剂制备方法用于说明这些制剂方法的使用。
实施方式之一,一种制备缓释微囊制剂的方法,是将粉碎的芯材(优选β-丙氨酸),均匀分散在热融的释放材料中;雾化;冷却。
实施方式之二,一种制备缓释微囊制剂的方法,是首先将释放材料热融,并保证雾化前处于熔融状态以顺利雾化,在流化床中采用顶喷或底喷工艺,对芯材进行包衣。
所述顶喷工艺为:进风温度45~73℃,风量20~50m3/h,使β-丙氨酸处于良好的流化状态,雾化压力0.1~0.3MPa,流速3~20ml/min,为了防止粘连,流速要逐步升高至合适水平。
所述底喷工艺为:进风温度45~73℃,风量20~50m3/h,调节导流管下端与分布板间距,使β-丙氨酸处于良好的流化状态,雾化压力0.1~0.3MPa,流速3~20ml/min,为了防止粘连,流速要逐步升高至合适水平。
实施方式之三,一种制备缓释微囊制剂的方法,包括如下步骤:
释放材料与芯材置于配有夹套保温***的高速搅拌器中,升温至45~73℃,并以1000~2000RPM转速搅拌,熔化的释放材料随搅拌均匀的涂覆于β-丙氨酸表面,降低转速并降温,冷却固化。
此外,本发明所述的优化包埋的微囊制剂及相应方法中,还可以根据活性成分及制剂的需要,向释放材料适当加入助剂,这些助剂可举例但不限于赋形剂、抗氧化剂、粘合剂、增稠剂、稀释剂、稳定剂、助流剂中的一种或多种。所述助剂的用量可以结合本领域现有技术确定。
本发明所述的优化包埋的微囊制剂,可应用于食品药品各领域,并根据需求进一步加工成为各种剂型,比如硬胶囊、片剂、冲剂等。
以下述非限制性实施例对本发明做进一步说明,以便于本领域的普通技术人员更全面地理解本发明,但不应理解为对本发明任何形式的限制。如无特殊说明,本申请中采用下述参数的测量方法。
表面活性成分的测定方法:5g待测微囊产品加入到锥形瓶中,向其中加入50ml纯净水,转摇20s后过滤,重复洗涤一次,合并滤液,旋蒸脱除纯净水,剩余固体的干重与待测微囊产品的质量比即为表面活性成分的含量,以百分比表示。
活性成分的释放度的评价,其测定方法为:USP〈711〉DISSOLUTIO,采用Apparatus2,转速50rpm,按DELAYED-RELEASE DOSAGE FORMS方法B进行pH6.8磷酸缓冲液中的释放度实验。
吸湿性评价方法为:中国药典2010版中附录XIX J药物引湿性试验指导原则进行,概述为:受试药物在25±1℃,相对湿度为80%±2%条件下4h的质量增重率。
实施例1
将350g氢化棕榈油加热熔融,保温40min。350g抗坏血酸置于上述溶液中搅拌至形成稳定均相溶液,并将混合物通过雾化器喷雾到温度为10摄氏度的冷空气中形成珠粒状的微囊,风量260m3/h,雾化压力0.2MPa,流速10ml/min,珠粒在冷空气中滞留沸腾操作时间20min至粉末自由流动,获得缓释产品A,其抗坏血酸的含量50.0%,其表面活性成分含量为16.9%,其引湿性为18.1%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为23.5%、26.7%、30.1%、35.2%、36.9%、38.2%和43.2%。
实施例2
将600g氢化棕榈油和氢化大豆油(质量比7:1)加热熔融,然后加入单双棕榈酸甘油酯(单脂肪酸甘油酯:双脂肪酸甘油酯的摩尔比为1:1.2)0.6g,搅拌至完全溶解,保温60min。1400gβ-丙氨酸置于流化床中,并用高压泵将上述溶液从流化床顶部喷入。流化床进风温度43℃,风量20m3/h,雾化压力0.1MPa,流速3ml/min,操作时间100min,获得缓释产品B,其β-丙氨酸的含量73.2%,其表面活性成分含量为12.3%,其引湿性为8.9%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为19.7%、23.5%、27.5%、30.0%、35.2%、37.6%和42.4%。
实施例3
将1000g氢化棕榈油和氢化葵花油(质量比2:1)加热熔融,然后加入单双棕榈酸甘油酯(单脂肪酸甘油酯:双脂肪酸甘油酯的摩尔比为1:0.2)2g,搅拌至完全溶解,保温60min。1400gβ-丙氨酸置于流化床中,并用高压泵将上述溶液从流化床顶部喷入。流化床进风温度73℃,风量50m3/h,雾化压力0.3MPa,流速20ml/min,操作时间120min,获得缓释产品C,其β-丙氨酸的含量为60.7%其表面活性成分含量为0.8%,其引湿性为2.1%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为5.6%、2.8%、5.6%、8.4%、11.2%、16.8%和17.9%。
实施例4
将1000g氢化棕榈油和氢化棉籽油(质量比3:1)加热熔融,然后加入单双硬脂酸甘油酯(单脂肪酸甘油酯:双脂肪酸甘油酯的摩尔比为1:0.9)10g,搅拌至完全溶解,保温60min。加入1400g L-精氨酸于熔融的释放材料中,升温至45℃,并以1000RPM转速搅拌,熔化的释放材料随搅拌均匀的涂覆于L-精氨酸表面,降低转速并降温,冷却固化,操作时间120min,获得缓释产品D,其L-精氨酸的含量为60.5%,其表面活性成分含量为0.6%,其引湿性为2.3%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为3.8%、5.8%、6.6%、8.5%、7.6%、11.3%和15.5%。
实施例5
将200g氢化棕榈油(熔点67℃)加热熔融,然后加入单双脂肪酸甘油酯(单棕榈酸甘油酯:双棕榈酸甘油酯:单硬脂酸甘油酯:双硬脂酸甘油酯的摩尔比为1:1:1:2)6g,搅拌至完全溶解,保温40min。800g抗坏血酸置于流化床中,并用高压泵将上述溶液从流化床底部雾化喷入。流化床进风温度73℃,风量20m3/h,雾化压力0.1MPa,流速3ml/min,操作时间90min,获得缓释产品E,其抗坏血酸的含量为77.3%,其表面活性成分含量为1.1%,其引湿性为3.9%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为6.7%、7.5%、8.8%、8.9%、10.1%、16.7%和18.1%。
实施例6
将200g氢化棕榈油(熔点67℃)加热熔融,然后加入单双脂肪酸甘油酯(单棕榈酸甘油酯:双棕榈酸甘油酯的摩尔比为1:0.6)10g,搅拌至完全溶解,保温40min。800g抗坏血酸置于流化床中,并用高压泵将上述溶液从流化床底部雾化喷入。流化床进风温度45℃,风量50m3/h,雾化压力0.3MPa,流速20ml/min,操作时间90min,获得缓释产品F,其抗坏血酸的含量为78.5%,其表面活性成分含量为2.8%,其引湿性为4.7%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为7.4%、8.3%、8.9%、10.6%、15.3%、19.7%和22.2%。
实施例7
将200g氢化棕榈油(熔点67℃)加热熔融,然后加入单双脂肪酸甘油酯(单棕榈酸甘油酯:双棕榈酸甘油酯的摩尔比为1:1.0)1.0g,搅拌至完全溶解,保温40min。670g维生素B3置于流化床中,并用高压泵将上述溶液从流化床底部雾化喷入。流化床进风温度50℃,风量47m3/h,雾化压力0.3MPa,流速18ml/min,操作时间100min,获得缓释产品G,其维生素B3的含量为71.2%,其表面活性成分含量为0.9%,其引湿性为3.5%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为4.5%、4.3%、6.7%、8.2%、8.3%、12.7%和16.2%。
实施例8
将500g氢化棕榈油和氢化玉米油(质量比4:1)加热熔融,然后加入单双硬脂酸甘油酯(单硬脂酸甘油酯:双硬脂酸甘油酯的摩尔比为1:0.5)2g,搅拌至完全溶解,保温40min。800g L-精氨酸置于流化床中,并用高压泵将上述溶液从流化床底部雾化喷入。流化床进风温度45℃,风量50m3/h,雾化压力0.3MPa,流速20ml/min,操作时间90min,获得缓释产品H,其L-精氨酸的含量为60.6%,其表面活性成分含量为1.5%,其引湿性为3.0%,其第1、2、3、4、5、6、8小时的释放度(pH6.8磷酸缓冲液)分别为7.2%、7.7%、9.8%、11.1%、13.5%、17.7%和19.6%。
实施例9
将1000g氢化棕榈油和氢化玉米油(质量比3:1)加热熔融,然后加入单双硬脂酸甘油酯(单脂肪酸甘油酯:双脂肪酸甘油酯的摩尔比为1:1.0)70g,加入,1.08kg左旋肉碱于熔融的释放材料中,升温至73℃,并以2000RPM转速搅拌,熔化的释放材料随搅拌均匀的涂覆于左旋肉碱表面,降低转速并降温,冷却固化,操作时间120min,获得缓释产品I,其左旋肉碱的含量为95.0%,其表面活性成分含量为23.2%,其引湿性为21.3%,其第1、2、3、4小时的释放度(pH6.8磷酸缓冲液)分别为43.2%、65.5%、87.3%和99.2%。
从上述实施例结果可见,在添加量范围内,单双脂肪酸甘油酯的添加可进一步提高包埋效率,主要体现在表面芯材含量,引湿性及8h内的释放度进一步降低,这表明芯材被包埋的更完全。
Claims (8)
1.优化包埋的微囊制剂,以壁材和壁材助剂的混合物作为释放材料,其特征在于,所述的壁材助剂是脂肪酸甘油酯;
所述的脂肪酸甘油酯选自单硬脂酸甘油酯、双硬脂酸甘油酯、单棕榈酸甘油酯、双棕榈酸甘油酯,及其中任意2种或2种以上的混合物;
所述的释放材料中脂肪酸甘油酯的质量含量为0.2~5%;
所述的壁材是氢化植物油。
2.权利要求1所述的微囊制剂,其特征在于,所述的脂肪酸甘油酯是单脂肪酸甘油酯与双脂肪酸甘油酯按照摩尔比1:0.2~1.5的混合物。
3.权利要求1所述的微囊制剂,其特征在于,所述的壁材是氢化棕榈油。
4.权利要求3所述的微囊制剂,其特征在于,所述的脂肪酸甘油酯和氢化棕榈油的质量比为1:20~500。
5.权利要求1所述的微囊制剂,其特征在于,所述的微囊制剂的芯材选自氨基酸和维生素。
6.权利要求5所述的微囊制剂,其特征在于,所述的芯材选自β-丙氨酸、α-丙氨酸、精氨酸、左旋肉碱、维生素C和维生素B族。
7.权利要求6所述的微囊制剂,其特征在于,所述的芯材是β-丙氨酸。
8.权利要求1~7中任一权利要求所述的微囊制剂,其特征在于,所述的释放材料与芯材的比例是1:1~19。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201511019154.6A CN105560211B (zh) | 2015-12-30 | 2015-12-30 | 优化包埋的微囊制剂 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201511019154.6A CN105560211B (zh) | 2015-12-30 | 2015-12-30 | 优化包埋的微囊制剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105560211A CN105560211A (zh) | 2016-05-11 |
CN105560211B true CN105560211B (zh) | 2019-06-14 |
Family
ID=55871236
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201511019154.6A Active CN105560211B (zh) | 2015-12-30 | 2015-12-30 | 优化包埋的微囊制剂 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105560211B (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109820836A (zh) * | 2019-03-22 | 2019-05-31 | 大连医诺生物股份有限公司 | 左旋肉碱缓释微囊粉及其制备方法 |
CN112931560A (zh) * | 2020-11-20 | 2021-06-11 | 广州新拓克生物科技有限公司 | 一种植酸酶-vc微丸制剂及其制备方法与应用 |
CN115428822B (zh) * | 2021-06-02 | 2024-03-19 | 南通醋酸化工股份有限公司 | 一种固体缓释型防腐剂微米包埋体的制备方法和应用 |
CN113693166A (zh) * | 2021-08-19 | 2021-11-26 | 浙江万方生物科技有限公司 | 一种奶牛专用分段式缓释矿物元素棒及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0626172A1 (en) * | 1993-05-28 | 1994-11-30 | ASCOR CHIMICI S.r.l. | Veterinary composition for treating and/or preventing infections and deseases |
CN1568181A (zh) * | 2001-10-09 | 2005-01-19 | 弗拉梅技术公司 | 用于延时和受控释放药物活性成分的微粒口服盖仑制剂 |
CN102427740A (zh) * | 2009-03-26 | 2012-04-25 | 先进生物营养公司 | 生物活性物质的微囊化及其制造方法 |
CN102438589A (zh) * | 2009-03-09 | 2012-05-02 | 益生菌股份公司 | 用于儿科应用的含益生菌的油性悬浮液 |
-
2015
- 2015-12-30 CN CN201511019154.6A patent/CN105560211B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0626172A1 (en) * | 1993-05-28 | 1994-11-30 | ASCOR CHIMICI S.r.l. | Veterinary composition for treating and/or preventing infections and deseases |
CN1568181A (zh) * | 2001-10-09 | 2005-01-19 | 弗拉梅技术公司 | 用于延时和受控释放药物活性成分的微粒口服盖仑制剂 |
CN102438589A (zh) * | 2009-03-09 | 2012-05-02 | 益生菌股份公司 | 用于儿科应用的含益生菌的油性悬浮液 |
CN102427740A (zh) * | 2009-03-26 | 2012-04-25 | 先进生物营养公司 | 生物活性物质的微囊化及其制造方法 |
Also Published As
Publication number | Publication date |
---|---|
CN105560211A (zh) | 2016-05-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105560211B (zh) | 优化包埋的微囊制剂 | |
US20230330032A1 (en) | Microencapsulation process and product | |
KR102170339B1 (ko) | 신규 코팅 시스템 | |
CN102613298B (zh) | 一种月桂酸单甘油酯微胶囊及其制备方法和应用 | |
EP2986141B1 (en) | Encapsulation of an oil containing unsaturated fatty acids | |
CN105663081B (zh) | 微囊化β-丙氨酸 | |
JP2005522313A5 (zh) | ||
KR20060095863A (ko) | 수용성 의약을 함유하는 제약학적 조성물 | |
CN105434402B (zh) | 优化释放的缓释微囊 | |
RU2009124462A (ru) | Способ производства порошкообразных масел | |
JP2005263948A (ja) | 油溶性物質含有カルシウム成分粉末の製造方法 | |
CN107997183B (zh) | 微囊化缓释支链氨基酸 | |
CA2780948C (en) | A process for converting a solid (meth)acrylate copolymer into a dispersed form by means of a dispersing agent | |
DE10260921A1 (de) | Verfahren zum Überziehen von Substraten für pharmazeutische Anwendungen mit einem Gemisch aus zwei filmbildenden Überzugsmitteln | |
CN105852131A (zh) | 制备符合有机食品加工标准的鱼油微胶囊的方法 | |
CN107412190A (zh) | 一种大蒜素复方微胶囊及其制备方法 | |
Leonel et al. | Production and characterization of lipid microparticles produced by spray cooling encapsulating a low molar mass hydrophilic compound | |
KR20200007822A (ko) | 고형 입자 | |
CA2793783C (en) | Novel coating system | |
CN106511125A (zh) | 佩兰复方固态精油及其用途和其胶囊制备方法 | |
CN109627458A (zh) | 一种含季铵基(甲基)丙烯酸酯共聚物水分散体的制备方法 | |
DE10260920A1 (de) | Verfahren zur Herstellung von Arnzeiformen oder Nahrungsergänzungsmitteln mit pigmentierten Polymerüberzügen | |
WO2020182792A1 (en) | Coated coacervate capsules | |
RU2557526C1 (ru) | Способ получения микрокапсул рыбных жиров | |
CN103768609B (zh) | 一种药用复合聚合物材料水分散液及应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB02 | Change of applicant information |
Address after: 116600 No. 49 economic and Technological Development Zone, Liaoning, Dalian Applicant after: Dalian promise biological Limited by Share Ltd Address before: 116600 No. 49 economic and Technological Development Zone, Liaoning, Dalian Applicant before: Dalian Innobioactives Co., Ltd. |
|
CB02 | Change of applicant information | ||
GR01 | Patent grant | ||
GR01 | Patent grant |