CN112292118A - 耐湿性益生菌颗粒剂及其产生方法 - Google Patents
耐湿性益生菌颗粒剂及其产生方法 Download PDFInfo
- Publication number
- CN112292118A CN112292118A CN201980041815.5A CN201980041815A CN112292118A CN 112292118 A CN112292118 A CN 112292118A CN 201980041815 A CN201980041815 A CN 201980041815A CN 112292118 A CN112292118 A CN 112292118A
- Authority
- CN
- China
- Prior art keywords
- coating
- acid
- starch
- probiotic
- hps
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000006041 probiotic Substances 0.000 title claims abstract description 40
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 40
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 239000008187 granular material Substances 0.000 title description 8
- 229920002472 Starch Polymers 0.000 claims abstract description 41
- 239000008107 starch Substances 0.000 claims abstract description 41
- 235000019698 starch Nutrition 0.000 claims abstract description 41
- 239000003094 microcapsule Substances 0.000 claims abstract description 33
- GUOCOOQWZHQBJI-UHFFFAOYSA-N 4-oct-7-enoxy-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)OCCCCCCC=C GUOCOOQWZHQBJI-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229920000642 polymer Polymers 0.000 claims abstract description 28
- 239000007962 solid dispersion Substances 0.000 claims abstract description 12
- 244000005700 microbiome Species 0.000 claims abstract description 9
- 239000011247 coating layer Substances 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 59
- 235000019868 cocoa butter Nutrition 0.000 claims description 51
- 229940110456 cocoa butter Drugs 0.000 claims description 51
- 241000186000 Bifidobacterium Species 0.000 claims description 41
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 41
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 37
- 238000000576 coating method Methods 0.000 claims description 34
- 239000011248 coating agent Substances 0.000 claims description 22
- 230000008569 process Effects 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 19
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 16
- 239000000194 fatty acid Substances 0.000 claims description 16
- 229930195729 fatty acid Natural products 0.000 claims description 16
- 150000004665 fatty acids Chemical class 0.000 claims description 16
- 239000012153 distilled water Substances 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 12
- 235000019197 fats Nutrition 0.000 claims description 12
- 230000005540 biological transmission Effects 0.000 claims description 10
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 7
- 235000021355 Stearic acid Nutrition 0.000 claims description 6
- 239000003240 coconut oil Substances 0.000 claims description 6
- 235000019864 coconut oil Nutrition 0.000 claims description 6
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 6
- 150000002191 fatty alcohols Chemical class 0.000 claims description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 6
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- 239000008117 stearic acid Substances 0.000 claims description 6
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 5
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 3
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 3
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 3
- 239000005639 Lauric acid Substances 0.000 claims description 3
- 239000005642 Oleic acid Substances 0.000 claims description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 3
- 235000019482 Palm oil Nutrition 0.000 claims description 3
- 235000021314 Palmitic acid Nutrition 0.000 claims description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229920001400 block copolymer Polymers 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- QSGDGGWTDYSGCY-UHFFFAOYSA-N hexadecaneperoxoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)OO QSGDGGWTDYSGCY-UHFFFAOYSA-N 0.000 claims description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 claims description 3
- 239000010514 hydrogenated cottonseed oil Substances 0.000 claims description 3
- 239000008173 hydrogenated soybean oil Substances 0.000 claims description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 3
- 239000000787 lecithin Substances 0.000 claims description 3
- 235000010445 lecithin Nutrition 0.000 claims description 3
- 229940067606 lecithin Drugs 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 3
- 239000002540 palm oil Substances 0.000 claims description 3
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 claims description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 3
- 150000003904 phospholipids Chemical class 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 229920000728 polyester Polymers 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 235000003441 saturated fatty acids Nutrition 0.000 claims description 3
- 150000004671 saturated fatty acids Chemical class 0.000 claims description 3
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 claims description 3
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims description 3
- 150000005691 triesters Chemical class 0.000 claims description 3
- SAEGZLLMRADAGL-UHFFFAOYSA-N 1-hydroxyoctacosyl 2-hydroxyoctadecanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCC(O)OC(=O)C(O)CCCCCCCCCCCCCCCC SAEGZLLMRADAGL-UHFFFAOYSA-N 0.000 claims description 2
- 150000002009 diols Chemical class 0.000 claims 1
- KCYQMQGPYWZZNJ-BQYQJAHWSA-N hydron;2-[(e)-oct-1-enyl]butanedioate Chemical compound CCCCCC\C=C\C(C(O)=O)CC(O)=O KCYQMQGPYWZZNJ-BQYQJAHWSA-N 0.000 claims 1
- 241000894006 Bacteria Species 0.000 description 32
- 239000000203 mixture Substances 0.000 description 27
- 235000013305 food Nutrition 0.000 description 23
- 238000012360 testing method Methods 0.000 description 22
- 239000000243 solution Substances 0.000 description 21
- 238000009472 formulation Methods 0.000 description 20
- 241000186012 Bifidobacterium breve Species 0.000 description 13
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 13
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 13
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 235000013350 formula milk Nutrition 0.000 description 11
- -1 hydroxyoctacosanol hydroxystearate (hydroxyeicosanyl hydroxystearate) Chemical compound 0.000 description 11
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 10
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 10
- 239000002245 particle Substances 0.000 description 9
- 241001134770 Bifidobacterium animalis Species 0.000 description 8
- 241000901050 Bifidobacterium animalis subsp. lactis Species 0.000 description 8
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 8
- 230000004888 barrier function Effects 0.000 description 8
- 239000011230 binding agent Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000011149 active material Substances 0.000 description 7
- 229940118852 bifidobacterium animalis Drugs 0.000 description 7
- 239000008199 coating composition Substances 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 239000001856 Ethyl cellulose Substances 0.000 description 6
- 229940009289 bifidobacterium lactis Drugs 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 235000019325 ethyl cellulose Nutrition 0.000 description 6
- 229920001249 ethyl cellulose Polymers 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- 230000002209 hydrophobic effect Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000004584 weight gain Effects 0.000 description 6
- 235000019786 weight gain Nutrition 0.000 description 6
- 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 4
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 235000013365 dairy product Nutrition 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- ZIWDVJPPVMGJGR-UHFFFAOYSA-N n-ethyl-2-methylprop-2-enamide Chemical compound CCNC(=O)C(C)=C ZIWDVJPPVMGJGR-UHFFFAOYSA-N 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 238000013112 stability test Methods 0.000 description 4
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- 241001608472 Bifidobacterium longum Species 0.000 description 3
- 229920000896 Ethulose Polymers 0.000 description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 3
- 241000186660 Lactobacillus Species 0.000 description 3
- 241000917009 Lactobacillus rhamnosus GG Species 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 229920002774 Maltodextrin Polymers 0.000 description 3
- 239000005913 Maltodextrin Substances 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000012159 carrier gas Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229920001577 copolymer Chemical class 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 description 3
- 239000007888 film coating Substances 0.000 description 3
- 238000009501 film coating Methods 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 3
- 229940039696 lactobacillus Drugs 0.000 description 3
- 229940059406 lactobacillus rhamnosus gg Drugs 0.000 description 3
- 229940035034 maltodextrin Drugs 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000007909 melt granulation Methods 0.000 description 3
- 230000002906 microbiologic effect Effects 0.000 description 3
- 244000005706 microflora Species 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000012466 permeate Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- RESPXSHDJQUNTN-UHFFFAOYSA-N 1-piperidin-1-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCCCC1 RESPXSHDJQUNTN-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- CCIDRBFZPRURMU-UHFFFAOYSA-N 2-methyl-n-propylprop-2-enamide Chemical compound CCCNC(=O)C(C)=C CCIDRBFZPRURMU-UHFFFAOYSA-N 0.000 description 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000194036 Lactococcus Species 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229940081735 acetylcellulose Drugs 0.000 description 2
- 150000003926 acrylamides Chemical class 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000004378 air conditioning Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 229940009291 bifidobacterium longum Drugs 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000021001 fermented dairy product Nutrition 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229940014259 gelatin Drugs 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000008206 lipophilic material Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical class CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- FIBUWQFQYAAXHD-UHFFFAOYSA-N n-cyclopropyl-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NC1CC1 FIBUWQFQYAAXHD-UHFFFAOYSA-N 0.000 description 2
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 2
- 229940049964 oleate Drugs 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229920001977 poly(N,N-diethylacrylamides) Polymers 0.000 description 2
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 description 2
- 229920002246 poly[2-(dimethylamino)ethyl methacrylate] polymer Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 2
- 229960000620 ranitidine Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229960003188 temazepam Drugs 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 235000013618 yogurt Nutrition 0.000 description 2
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- IZCXQDYKFFBERI-UHFFFAOYSA-N 1-(diethylamino)ethyl 2-methylprop-2-enoate Chemical group CCN(CC)C(C)OC(=O)C(C)=C IZCXQDYKFFBERI-UHFFFAOYSA-N 0.000 description 1
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- JWYVGKFDLWWQJX-UHFFFAOYSA-N 1-ethenylazepan-2-one Chemical compound C=CN1CCCCCC1=O JWYVGKFDLWWQJX-UHFFFAOYSA-N 0.000 description 1
- WLPAQAXAZQUXBG-UHFFFAOYSA-N 1-pyrrolidin-1-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCCC1 WLPAQAXAZQUXBG-UHFFFAOYSA-N 0.000 description 1
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- YQIGLEFUZMIVHU-UHFFFAOYSA-N 2-methyl-n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C(C)=C YQIGLEFUZMIVHU-UHFFFAOYSA-N 0.000 description 1
- AGBXYHCHUYARJY-UHFFFAOYSA-N 2-phenylethenesulfonic acid Chemical compound OS(=O)(=O)C=CC1=CC=CC=C1 AGBXYHCHUYARJY-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920003114 HPC-L Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920001908 Hydrogenated starch hydrolysate Polymers 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 229920002000 Xyloglucan Polymers 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 235000008452 baby food Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920003118 cationic copolymer Polymers 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229920001531 copovidone Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 241000186254 coryneform bacterium Species 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 238000005868 electrolysis reaction Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 229940059112 ethulose Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000021107 fermented food Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 235000021474 generally recognized As safe (food) Nutrition 0.000 description 1
- 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- UACSZOWTRIJIFU-UHFFFAOYSA-N hydroxymethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCO UACSZOWTRIJIFU-UHFFFAOYSA-N 0.000 description 1
- GJIDOLBZYSCZRX-UHFFFAOYSA-N hydroxymethyl prop-2-enoate Chemical compound OCOC(=O)C=C GJIDOLBZYSCZRX-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000905 isomalt Substances 0.000 description 1
- 235000010439 isomalt Nutrition 0.000 description 1
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol 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-JVCRWLNRSA-N 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000012009 microbiological test Methods 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 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
- JMCVCHBBHPFWBF-UHFFFAOYSA-N n,n-diethyl-2-methylprop-2-enamide Chemical compound CCN(CC)C(=O)C(C)=C JMCVCHBBHPFWBF-UHFFFAOYSA-N 0.000 description 1
- ADTJPOBHAXXXFS-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]prop-2-enamide Chemical group CN(C)CCCNC(=O)C=C ADTJPOBHAXXXFS-UHFFFAOYSA-N 0.000 description 1
- VQGWOOIHSXNRPW-UHFFFAOYSA-N n-butyl-2-methylprop-2-enamide Chemical compound CCCCNC(=O)C(C)=C VQGWOOIHSXNRPW-UHFFFAOYSA-N 0.000 description 1
- LCXIFAOALNZGDO-UHFFFAOYSA-N n-cyclopropylprop-2-enamide Chemical compound C=CC(=O)NC1CC1 LCXIFAOALNZGDO-UHFFFAOYSA-N 0.000 description 1
- SWPMNMYLORDLJE-UHFFFAOYSA-N n-ethylprop-2-enamide Chemical compound CCNC(=O)C=C SWPMNMYLORDLJE-UHFFFAOYSA-N 0.000 description 1
- 235000008486 nectar Nutrition 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002417 nutraceutical Substances 0.000 description 1
- 235000021436 nutraceutical agent Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229920002432 poly(vinyl methyl ether) polymer Chemical class 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920001451 polypropylene glycol Chemical class 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229940075065 polyvinyl acetate Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 230000013777 protein digestion Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 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
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000020138 yakult Nutrition 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- 229940093612 zein Drugs 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
- A61K9/48—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
- A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
-
- 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
- A23P10/30—Encapsulation of particles, e.g. foodstuff additives
-
- 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
- A23P10/30—Encapsulation of particles, e.g. foodstuff additives
- A23P10/35—Encapsulation of particles, e.g. foodstuff additives with oils, lipids, monoglycerides or diglycerides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/5089—Processes
-
- 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
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
- A23V2200/3204—Probiotics, living bacteria to be ingested for action in the digestive tract
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K2035/11—Medicinal preparations comprising living procariotic cells
- A61K2035/115—Probiotics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Botany (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
提供了一种益生菌微胶囊,所述益生菌微胶囊包括:芯,所述芯包含益生菌微生物;以及包衣层,所述包衣层包含混合固体分散体,所述混合固体分散体包含均匀地分散在水溶性成膜聚合物和可食用介质内的可食用脂肪分子,其中所述可食用介质是辛烯基琥珀酸淀粉酯。
Description
发明领域
本发明涉及益生菌颗粒剂的包衣的领域,并且更特别地,涉及意图混合在具有相对高水平的水活度(water activity)的食品中的益生菌颗粒剂。
发明背景
当活性材料被水的存在所不利地影响时,保护营养剂型和营养制品剂型免受环境水分的影响是重要的。水分的负面作用可能发生在常见生产工艺期间,诸如涉及湿法制粒和/或湿法包衣的工艺期间。可选择地,水分可能在储存期间损害活性材料,并且对最终产品的贮存寿命(shelf life)产生负面影响。
关于益生菌,水分在许多益生菌的稳定性和贮存寿命方面是特别重要的因素。在许多情况下,将这样的益生菌暴露于一定水平的湿度可以导致细菌失活。因此,可以掺入这样的细菌的食品,特别是具有高水平的水活度的食品的范围将受到限制,并且贮存寿命将显著缩短。
旨在限制对活性材料的损害的常用方法包括将含有水分敏感活性材料的剂型包装在不同的包装元件中,诸如微胶囊、片剂、胶囊等中。然而,特别是在气候非常潮湿的地方,因为被捕获在上文提及的包装内侧的水分,特定包装不能提供完全的防潮保护。另一种防止或减少可能由水分引起的损害并且降低对特定包装的需求的方式是用具有水分屏障性质的材料包被固体剂型。
这样的材料基本上具有低水蒸气渗透(water vapour permeation,WVP)或低水蒸气转移率(water vapor transition rate,WVTR)。这些包衣通常不影响剂型的基本性质,诸如活性材料的崩解时间和释放概况。水分敏感药物的实例包括阿托伐他汀(atorvastatin)、雷尼替丁(ranitidine)、替马西泮(temazepam)、大多数维生素、多种草药、不饱和脂肪酸和益生菌。由于水分而可能发生的损害可以包括,例如,活性材料因水解而降解、益生菌的破坏或CFU(菌落形成单位)值的显著降低、剂型在储存时外观的变化、剂型的崩解和/或溶解时间的变化。因此,应用水分屏障包衣来保护剂型免受这样的损害。
为了实现水分屏障包衣,通常使用疏水性水不溶性聚合物。通常用于该目的的聚合物是聚乙酸乙烯酯、玉米醇溶蛋白、虫胶、邻苯二甲酸乙酸纤维素(CAP)、E 100(其为基于2:1:1比例的甲基丙烯酸二甲基氨基乙酯、甲基丙烯酸丁酯和甲基丙烯酸甲酯的阳离子共聚物)、乙基纤维素(EC)及类似物。然而,这样的聚合物在施用之后延长剂型在体内的崩解,并且因此延迟活性材料或益生菌的释放。同样,用这些聚合物进行包被需要涉及使用有机溶剂,这是不期望的,因为这样的工艺增加与用以安全地处理这样的材料的空调设备(air conditioning equipment)、防爆准备等相关的另外的费用。另一种实现水分屏障包衣的方式是将水溶性聚合物与亲脂性物质组合。疏水性或亲脂性物质颗粒将在包衣或膜形成之后被包埋在水溶性膜中。尽管膜中亲脂性物质颗粒的存在可以降低水蒸气转移,但是亲脂性物质颗粒不能覆盖膜的所有区域,并且因此水蒸气仍然可以容易地渗透通过颗粒之间的空间。
一般而言,益生菌是对水分易感的微生物,并且存在特定的菌株,这些菌株比其他菌株更容易受伤害。
BB-12(由Chris Hansen培养的乳双歧杆菌(Bifidobacterium lactis)的特定菌株)和LGG(由Chris Hansen培养的鼠李糖乳杆菌(Lactobacillus rhamnosus,LGG)的特定菌株),被认为对水分高度易感,并且特别是对具有高水活度(aw)的环境高度易感。因此,当这些细菌与具有相对高水平的水活度的食品组合时,这些细菌的存活力(survivability)在非常短的时间内显著降低。
双歧杆菌是一种厌氧的棒状革兰氏阳性细菌,通常存在于人类的、婴儿的和成人的结肠中(Simon GL和Gorbach SL.Intestinal flora in health anddisease.Gastroenterol,1984;86:174-193)。已经报告了双歧杆菌的有益作用,包括通过防止病原体定植来改善肠道区系(intestinal flora)、活化免疫系统、提高蛋白质消化和改善腹泻或便秘(Ishibashi N和Shimamura S.Bifidobacteria:Research anddevelopment in Japan.Food Technol,1993;6:126-136)。双歧杆菌已经在发酵食品中被消耗持续数十年,并且目前的商业菌株包括动物双歧杆菌(Bifidobacterium animalis,B.animalis)乳亚种菌株Bf-6、乳双歧杆菌(Bifidobacterium lactis,B.lactis)BB-12、乳双歧杆菌DR10(HNO19)、长双歧杆菌(Bifidobacterium longum,B.longum)BB536、短双歧杆菌(B.breve)Yakult、短双歧杆菌SBT-2928和短双歧杆菌C50。在美国,多种双歧杆菌物种已被确定为用于常规食品和婴儿配方奶粉的GRAS,包括:用于选定的食品的动物双歧杆菌乳亚种Bf-6(GRN 377;1011cfu/常规食品分量);用于4月龄及大于4月龄婴儿配方奶粉的乳双歧杆菌Bb-12(GRN 49;107-108cfu/g婴儿配方奶粉)以及用于选定的食品和婴儿配方奶粉的长双歧杆菌BB536(GRN 268;1010cfu/常规食品分量;1010cfu/g足月婴儿配方奶粉)。已知商业乳制品中对人类健康发挥有益作用的活双歧杆菌的最低水平为约105~107CFU/ml(CuiJH,Shim JM,Lee JS等人Gastric acid resistance of Lactobacilli andBifidobacteria in commercial drink and lipid yogurts.Kor J Microbiol,2000;36:161-165)。最近,存在越来越大的动机将双歧杆菌应用在婴儿食品中,尤其是粉状婴儿配方奶粉(PIF)中(Duncker,2013)。这主要是为了维持婴儿的有益的微生物区系(micro-flora)(尤其是在使天然微生物区系受损的抗生素治疗后)(Morinaga Milk IndustryCo.Ltd.Bifidobacteria&Health.Japan:1997年8月,第4页)。
短双歧杆菌M-16V(短双歧杆菌)是一种Y形革兰氏阳性厌氧菌。这种生物体保藏在比利时微生物协调保藏中心(Belgian Co-ordinated Collections of Microorganisms,BCCM),并命名为LMG 23729。已经在婴儿和成人的粪便中检测到短双歧杆菌。短双歧杆菌M-16V于1976年首次在日本商购可得。短双歧杆菌M-16V的原始冷冻培养物受到严格控制以确保菌株的纯度和稳定性。产品规格确保短双歧杆菌M-16V适合用于食品,包括足月婴儿配方奶粉、豁免足月婴儿配方奶粉(exempt term infant formula)和医疗食品。用短双歧杆菌M-16V培养物制成的成品可再现地满足组成标准,并且符合适于食品级成分的对污染物的限制。短双歧杆菌M-16V满足由联合国粮食及农业组织/世界卫生组织(FAO/WHO)关于评价微生物在食品中的益生菌用途的指南列举的安全标准。结果表明,短双歧杆菌M-16V无毒或不致病,并且因此在食品中使用是安全的。
动物双歧杆菌乳亚种(商业上也称为BB-12)在本文中将被称为“双歧杆菌”,是一种过氧化氢酶阴性的棒状细菌。动物双歧杆菌乳亚种在1983年保藏在Chr.Hansen的细胞培养库中。在分离时,双歧杆菌被认为属于两歧双歧杆菌(Bifidobacterium bifidum)物种。现代分子分类技术将BB-12重新分类为动物双歧杆菌,并且后来又重新分类为新的物种乳双歧杆菌。乳双歧杆菌物种后来被证明不满足物种标准,并且替代地作为亚种被包括在动物双歧杆菌中。现今,BB-12因此被分类为动物双歧杆菌乳亚种。尽管多年来名称有所变化,但菌株BB-12未变化。
双歧杆菌来源于Chr.Hansen的收藏的乳制品培养物(collection of dairyculture)。双歧杆菌是Chr.Hansen特别选择用于生产益生菌乳制品的菌株。双歧杆菌已在世界范围内用于婴儿配方奶粉、膳食补充剂和发酵乳制品。该菌株在技术上非常合适,表现出发酵活性、高耐氧性(high aerotolerance)、良好的稳定性以及高的耐酸性和耐胆汁性,也作为膳食补充剂中的冻干产品。此外,双歧杆菌对食品的味道、外观或口感没有不利影响,并且能够在益生菌食品中存活直至消耗。
Chr.Hansen是双歧杆菌的独家生产商,双歧杆菌始终是最重要且研究最广泛的益生菌菌株之一。这种特定菌株目前用于不同的膳食补充剂和食品,诸如婴儿配方奶粉和发酵乳制品。
鼠李糖乳杆菌是一种短的革兰氏阳性异型发酵兼性厌氧的不产生孢子的杆菌,通常以链出现。虽然鼠李糖乳杆菌GG(ATCC 53103)能够在胃和肠的酸和胆汁中存活,被声称定植于消化道,并且平衡肠微生物区系,但证据表明鼠李糖乳杆菌可能是暂时的习居菌(transient inhabitant),而不是土著性的。无论如何,鼠李糖乳杆菌GG被认为是可用于治疗多种疾病的益生菌,因为它在许多水平上起作用。鼠李糖乳杆菌GG与肠粘膜结合。
附图简述
根据下文给出的详述和附图,本发明将变得完全被理解,这些详述和附图仅通过说明和实例的方式给出,并且不意图限制本发明的范围。
图1描绘了展示保持在进行持续稳定性测试的相同条件的与未包衣的细菌相比的微胶囊化的细菌的水含量的图,该水含量还使用干燥失重(Loss-On-Dry,LOD)方法随时间进行测量。
发明概述
根据一些说明性实施方案,本文提供了益生菌微胶囊,所述益生菌微胶囊包括:芯,所述芯包含益生菌微生物;以及包衣层,所述包衣层包含混合固体分散体,所述混合固体分散体包含均匀地分散在水溶性成膜聚合物和可食用介质内的可食用脂肪分子,其中所述可食用介质是辛烯基琥珀酸淀粉酯。
根据一些说明性实施方案,水溶性成膜聚合物可以是羟丙基淀粉。
根据一些实施方案,益生菌微生物可以包括双歧杆菌。
根据一些实施方案,可食用脂肪分子可以选自包括以下的组:月桂酸、肉豆蔻酸、棕榈酸、棕榈酸酯、棕榈油酸酯、羟基棕榈酸酯、花生酸、油酸、硬脂酸、硬脂酸钠、硬脂酸钙、硬脂酸镁、羟基二十八醇羟基硬脂酸酯(hydroxyoctacosanyl hydroxystearate)、长链的油酸酯、脂肪酸的酯、脂肪醇、酯化的脂肪二醇、羟基化的脂肪酸、氢化脂肪酸(饱和或部分饱和的脂肪酸)、部分氢化大豆油、部分氢化棉籽油、脂肪族醇、磷脂质、卵磷脂、磷脂酰胆碱、脂肪酸的三酯、椰子油、氢化椰子油、可可脂(cacao butter);棕榈油;脂肪酸共晶体;甘油单酯和甘油二酯、泊洛沙姆、聚乙二醇和聚酯的嵌段共聚物或其组合。
根据一些优选的实施方案,可食用脂肪分子可以是可可脂(cocoa butter)和/或硬脂酸。
根据一些实施方案,混合固体分散体可以是单一混合固体分散体。
发明详述
根据一些说明性实施方案,提供了一种微胶囊(本文也称为颗粒剂),该微胶囊包括含有益生菌的芯和至少一层保护益生菌免受水分影响的包衣层。
根据一些说明性实施方案,颗粒剂可以被掺入食品中,主要是液体食品中,包括例如基于水的食品、液体婴儿配方奶粉、酸奶、乳制品、花蜜、果汁及类似物。
根据一些说明性实施方案,微胶囊可以优选地被掺入具有相对高水平的水活度的食品中。
根据一些说明性实施方案,益生菌可以包括意图当消耗时通常通过改善或恢复肠区系来提供健康益处的任何合适的活微生物,例如选自乳杆菌属(Lactobacillus)、双歧杆菌属、芽孢杆菌属(Bacillus)的属。
根据一些实施方案,益生菌优选地为双歧杆菌和/或LGG菌。
根据一些说明性实施方案,至少一层包衣可以包括含有混合固体分散体的特定密封膜包衣,在所述混合固体分散体中,可食用脂肪分子使用例如可食用介质均匀地分散在水溶性成膜聚合物内。
根据一些说明性实施方案,脂肪分子可以包括任何合适的可食用脂肪酸,包括例如月桂酸、肉豆蔻酸、棕榈酸、棕榈酸酯、棕榈油酸酯、羟基棕榈酸酯、花生酸、油酸、硬脂酸、硬脂酸钠、硬脂酸钙、硬脂酸镁、羟基二十八醇羟基硬脂酸酯、长链的油酸酯、脂肪酸的酯、脂肪醇、酯化的脂肪二醇、羟基化的脂肪酸、氢化脂肪酸(饱和或部分饱和的脂肪酸)、部分氢化大豆油、部分氢化棉籽油、脂肪族醇、磷脂质、卵磷脂、磷脂酰胆碱、脂肪酸的三酯、椰子油、氢化椰子油、可可脂;棕榈油;脂肪酸共晶体;甘油单酯和甘油二酯、泊洛沙姆、聚乙二醇和聚酯的嵌段共聚物或其组合。
根据一些实施方案,脂肪分子优选地是可可脂和/或硬脂酸。
根据一些说明性实施方案,水溶性成膜聚合物可以包括例如以下中的一种或更多种:羟丙基淀粉(HPS)、聚-N-取代的丙烯酰胺衍生物、聚环氧丙烷、聚乙烯基甲基醚、聚乙烯醇的部分乙酰化的产物、甲基纤维素(MC)、羟丙基纤维素(HPC)、甲基羟乙基纤维素(MHEC)、羟丙基甲基纤维素(HPMC)、羟丙基乙基纤维素(HPEC)、羟甲基丙基纤维素(HMPC)、乙基羟乙基纤维素(EHEC)(Ethulose)、羟乙基甲基纤维素(HEMC)、羟甲基乙基纤维素(HMEC)、丙基羟乙基纤维素(PHEC)、疏水地改性的羟乙基纤维素(NEXTON)、直链淀粉、支链淀粉、聚(有机膦氮烯)、木葡聚糖、合成弹性蛋白衍生蛋白质、以及用亲水性或疏水性单体进一步取代的任何上述聚合物。
根据一些实施方案,聚-N-取代的丙烯酰胺衍生物可以包括以下中的一种或更多种:聚(N-异丙基丙烯酰胺)(PNIPAM)、聚-N-丙烯酰哌啶、聚(N,N-二乙基丙烯酰胺)(PDEAAm)、聚(N-乙烯基己内酰胺)(PVCL)、聚[2-(二甲基氨基)乙基甲基丙烯酸酯](PDMAEMA)、聚(乙二醇)(PEG)、聚(环氧乙烷)(PEO)、PEG甲基丙烯酸酯聚合物(PEGMA)、聚-N-丙基甲基丙烯酰胺、聚-N-异丙基丙烯酰胺、聚-N-二乙基丙烯酰胺、聚-N-异丙基甲基丙烯酰胺、聚-N-环丙基丙烯酰胺、聚-N-丙烯酰吡咯烷、聚-N,N-乙基甲基丙烯酰胺、聚-N-环丙基甲基丙烯酰胺、聚-N-乙基丙烯酰胺、聚-N-取代的甲基丙烯酰胺衍生物、包含N-取代的丙烯酰胺衍生物和N-取代的甲基丙烯酰胺衍生物的共聚物,以及N-异丙基丙烯酰胺和丙烯酸的共聚物。
在一些说明性实施方案中,亲水性单体可以包括以下中的一种或更多种:N-乙烯基吡咯烷酮、乙烯基吡啶、丙烯酰胺、甲基丙烯酰胺、N-甲基丙烯酰胺、甲基丙烯酸羟乙酯、丙烯酸羟甲酯、丙烯酸羟乙酯、甲基丙烯酸羟甲酯、具有酸性基团的甲基丙烯酸和丙烯酸,以及这些酸的盐,乙烯基磺酸、苯乙烯磺酸、具有碱性基团的衍生物诸如甲基丙烯酸N,N-二甲基氨基乙酯、甲基丙烯酸N,N-二乙基氨基乙酯、N,N-二甲基氨基丙基-丙烯酰胺,以及这些衍生物的盐。
在一些说明性实施方案中,疏水性单体可以包括以下中的一种或更多种:丙烯酸乙酯、甲基丙烯酸甲酯和甲基丙烯酸缩水甘油酯;N-取代的烷基甲基丙烯酰胺衍生物,诸如N-正丁基甲基丙烯酰胺;氯乙烯、丙烯腈、苯乙烯、乙酸乙烯酯。
根据一些实施方案,水溶性成膜聚合物是HPS和/或HPC。
根据一些实施方案,可食用介质可以包括例如辛烯基琥珀酸淀粉酯(SOS)。
根据一些说明性实施方案,可食用介质可以降低水溶性成膜聚合物和可食用脂肪分子之间的界面张力。根据一些实施方案,降低表面张力可以产生水溶性成膜聚合物和可食用脂肪分子之间的紧密结合(integration),例如,确保形成环绕微胶囊的芯的均匀、牢固和完整的膜包衣。
根据一些实施方案,辛烯基琥珀酸淀粉酯包含至少两个部分,这些部分使得亲水性组分和疏水性组分能够令人惊讶地粘附。具体地,在一些实施方案中,辛烯基琥珀酸淀粉酯可以包括可以粘附到水溶性成膜聚合物的亲水性部分,以及粘附到可食用脂肪分子的至少一个疏水性部分。
根据一些实施方案,辛烯基琥珀酸淀粉酯的这些独特特征允许产生单一混合固体分散体,该单一混合固体分散体充当水分屏障,防止湿气渗透到所述微胶囊的芯中。
根据一些实施方案,混合固体分散体提供阻止水渗透到芯中的基本上均匀的包衣。
根据一些实施方案,例如,与分开的保护层相比,单一混合固体分散体可以提供更优异的性质,例如,分开的层可能例如在分层期间和/或由于每一层的非均匀覆盖而具有更高的湿气渗透可能性。
根据一些说明性实施方案,益生菌可以以范围在微胶囊重量的10%-60%w/w之间的量存在。
根据本发明的一些实施方案,芯还可以包含填料。填料的实例包括,但不限于,微晶纤维素,糖,诸如乳糖、葡萄糖、半乳糖、果糖或蔗糖;磷酸二钙;糖醇,诸如山梨糖醇、manitol、甘露糖醇、乳糖醇、木糖醇、异麦芽酮糖醇、赤藓糖醇和氢化淀粉水解物;玉米淀粉;马铃薯淀粉;羧甲基纤维素钠、乙基纤维素和乙酸纤维素、或其混合物。在优选的实施方案中,填料是乳糖。
根据一些说明性实施方案,填料可以以范围在微胶囊重量的60%-70%w/w之间的量存在。
根据本发明的一些实施方案,芯还可以包含粘合剂。
通过非限制性实例的方式,粘合剂的实例包括聚维酮(PVP:聚乙烯基吡咯烷酮)、共聚维酮(乙烯基吡咯烷酮和乙酸乙烯酯的共聚物)、聚乙烯醇、低分子量羟丙基甲基纤维素(HPMC)、低分子量羟丙基纤维素(HPC)、低分子量羟甲基纤维素(MC)、低分子量羧甲基纤维素钠、低分子量羟乙基纤维素、低分子量羟甲基纤维素、乙酸纤维素、明胶、水解明胶、聚环氧乙烷、阿拉伯胶、糊精、麦芽糖糊精、淀粉以及水溶性聚丙烯酸酯和聚甲基丙烯酸酯、低分子量乙基纤维素或其混合物。在优选的实施方案中,粘合剂是麦芽糖糊精。
根据一些说明性实施方案,粘合剂可以以范围在微胶囊重量的10%-15%w/w之间的量存在。
根据一些说明性实施方案,微胶囊可以被掺入到具有高水活度的食品中,而例如不损害包含在微胶囊内的益生菌。
水活度或aw是物质中水的蒸气分压除以水的标准状态蒸气分压。在食品科学领域,标准状态最常被定义为相同温度时纯水的蒸气分压。纯的蒸馏水具有正好为1的水活度。
根据一些说明性实施方案,本文提供了一种微胶囊制剂,该微胶囊制剂为易感益生菌提供优异的防湿气保护,以防止它们失活并且从而延长贮存寿命。这继而可以延长其中甚至将在高温掺入细菌的产品的贮存寿命。
这项初步研究为这种特定的微胶囊化提供稳健的概念证明,这种特定的微胶囊化被设计成在室温在具有相对高的湿度的环境中保护敏感益生菌。通过将微胶囊化的益生菌在室温长时间暴露于空气,以及使用LOD方法测定的水含量,证明该技术的可行性。同样,发现微胶囊化工艺是完全安全的,其中细菌的初始数量被保持与初始的数量相似。
根据一些说明性实施方案,本文提供了一种用于制备用于保护益生菌免受水分影响的微胶囊的方法,其中该方法包括:
制备包含双歧杆菌的微胶囊芯;
用包含低水蒸气透过率(WVTR)值的至少一层包衣包被芯;其中所述至少一层包衣包含羟丙基淀粉(HPS)、可可脂(CB)和辛烯基琥珀酸淀粉酯。
根据一些实施方案,所述方法可以包括:通过将HPS添加到加热的蒸馏水(85℃-90℃)中来制备HPS的5%w/w溶液;
将辛烯基琥珀酸淀粉酯添加到加热的蒸馏水中,并且继续地搅拌直至获得均匀的澄清溶液;以及将可可脂预熔化,同时使用机械搅拌器搅拌。
根据一些实施方案,在50℃将可可脂预熔化。
根据一些实施方案,使用均化器将所得到的辛烯基琥珀酸淀粉酯溶液和熔化的CB均化到HPS的5%w/w溶液中。
C)方法:
i)膜制备:基于羟丙基淀粉(HPS)作为成膜聚合物。
制备不同的膜制剂,并且通过水蒸气透过率(WVTR)进行表征。
精确地称量HPS、可可脂(CB)和辛烯基琥珀酸淀粉酯(商业上也称为Emfix)以获得一定比例的HPS:CB:辛烯基琥珀酸淀粉酯。表2呈现了本研究中制备的不同的膜的制剂,它们具有多种比例的HPS:CB:辛烯基琥珀酸淀粉酯。首先将期望量的HPS添加到加热的蒸馏水(85℃-90℃)中,同时使用磁力搅拌器混合,以制备5%w/w的聚合物。继续搅拌,直到获得均匀的澄清溶液(在85℃-90℃15min-30min)。然后将期望量的辛烯基琥珀酸淀粉酯添加到加热的蒸馏水中,继续搅拌直到获得均匀的澄清溶液。在50℃将可可脂预熔化,同时使用机械搅拌器搅拌。然后使用均化器将所得到的辛烯基琥珀酸淀粉酯溶液和熔化的CB均化到HPS的5%w/w溶液中持续90秒,均化器速度为3500RPM(均化器,HSIANG TAI MACHINERYINDUSTRY,型号:HG-300,最大速度-26000rpm)。然后将之后的分散体冷却至32℃-36℃,并且保持搅拌持续另外20分钟,以允许聚合物完全溶解。
实施例
实施例1-芯和包衣组合物实施方案-(基于溶液的芯形成)
芯和包衣两者的实例列于下表1中。
表1-芯和包衣实例
实施例2-包含双歧杆菌的芯的微胶囊化的方法
在一种实施方案中,微胶囊化的方法如下。
A)膜包衣的配制。
为了寻找提供最高屏障能力的正确制剂,制备包衣组分的多种组合并且在Versaperm Ltd.实验室(Maidenhead,UK)中测试水蒸气透过率(WVTR)。
B)双歧杆菌微胶囊化的制备。
首先,使用期望的制剂制备包含双歧杆菌的芯。然后,使用那些呈现出最低WVTR值的特定包衣制剂对所得到的芯进行包被。同样,微胶囊化工艺旨在发现特定包衣制剂是否也能够在工艺期间对芯进行包被,尽管它具有形成对于WVTR测试性能所需的游离膜的能力。来自这部分实验的结果表明,包衣工艺可以非常平稳且快速地发生,其中颗粒尺寸和颗粒尺寸分布仍然可以完美地处于所需的范围内。LOD(干燥失重)值可以被控制和调整在一定范围内,该范围能够实现细菌长期持续的稳定性。
C)方法:
i)膜制备:基于羟丙基淀粉(HPS)作为成膜聚合物。
制备不同的膜制剂,并且通过水蒸气透过率(WVTR)进行表征。
精确称量HPS、可可脂(CB)和辛烯基琥珀酸淀粉酯(商业上也称为Emfix)以获得一定比例的HPS:CB:辛烯基琥珀酸淀粉酯。表2呈现了本研究中制备的不同的膜的制剂,它们具有多种比例的HPS:CB:辛烯基琥珀酸淀粉酯。首先将期望量的HPS添加到加热的蒸馏水(85℃-90℃)中,同时使用磁力搅拌器混合,以制备5%w/w的聚合物。继续搅拌,直到获得均匀的澄清溶液(在85℃-90℃15min-30min)。然后将期望量的辛烯基琥珀酸淀粉酯添加到加热的蒸馏水中,继续搅拌直到获得均匀的澄清溶液。在50℃将可可脂预熔化,同时使用机械搅拌器搅拌。然后使用均化器将所得到的辛烯基琥珀酸淀粉酯溶液和熔化的CB均化到HPS的5%w/w溶液中持续90秒,均化器速度为3500RPM(均化器,HSIANG TAI MACHINERYINDUSTRY,型号:HG-300,最大速度-26000rpm)。然后将之后的分散体冷却至32℃-36℃,并且保持搅拌持续另外20分钟,以允许聚合物完全溶解。
最后将分散体倒入皮氏培养皿(Petrie dish)(100mm直径)中,并且在室温在通风橱中在气流下干燥持续至少96小时。
表2
表2示出了基于不同比例的HPS:CB:辛烯基琥珀酸淀粉酯的不同膜制剂的一些实施方案。
ii)膜制备:基于HPC(羟丙基纤维素)作为成膜聚合物。
精确称量HPC、可可脂(CB)和辛烯基琥珀酸淀粉酯以获得一定比例的HPC:CB:辛烯基琥珀酸淀粉酯。表3呈现了本研究中制备的不同的膜的制剂,它们具有多种比例的HPC:CB:辛烯基琥珀酸淀粉酯。首先将期望量的辛烯基琥珀酸淀粉酯添加到加热的蒸馏水中,继续搅拌直到获得均匀的澄清溶液。在50℃将可可脂预熔化,同时使用机械搅拌器搅拌。然后将所得到的混合物均化到HPC LF的5%w/w分散体中,如上文描述的,使用均化器在75℃的预加热的蒸馏水中制备该分散体。然后将之后的分散体冷却至低于聚合物的LCST,并且保持搅拌持续另外30分钟,以允许聚合物完全溶解。最后将分散体倒入皮氏培养皿(100mm直径)中,并且在室温在通风橱中在气流下干燥持续至少96小时。
表3
表3示出了基于不同比例的HPC:CB:辛烯基琥珀酸淀粉酯的不同膜制剂的一些实施方案。
iii)水蒸气透过率(WVTR)测试。
本测试的构思是基于指定条件下每单位时间透过单位面积的测试膜样本的水蒸气的量的测量。水蒸气透过率被表示为克/平方米,24小时[克/(m2·24h)]。配备有电解检测传感器的具有10cm2测量面积的Versaperm MkV数字WVTR仪表(Versaperm Ltd.,Maidenhead,UK)被用于测量不同膜的WVTR。该方法基于ISO 15106-3:2003。
测试1-测试在40℃、100%湿度进行持续24小时。
测试2-测试在室温(23-25℃)、100%湿度进行持续24小时。
iv)用于微胶囊化工艺的混合固体分散体游离膜的制备。
精确称量HPS、可可脂(CB)和辛烯基琥珀酸淀粉酯(辛烯基琥珀酸淀粉酯)以获得一定比例的HPS:CB:辛烯基琥珀酸淀粉酯。表4呈现了本研究中制备的不同的膜的制剂,它们具有多种比例的HPS:CB:辛烯基琥珀酸淀粉酯。首先将期望量的HPS添加到预加热的蒸馏水(85℃-90℃)中,同时使用磁力搅拌器混合,以制备5%w/w的聚合物。继续搅拌,直到获得均匀的澄清溶液(在85℃-90℃15min-30min)。
然后将期望量的辛烯基琥珀酸淀粉酯添加到加热的蒸馏水中,继续搅拌直到获得均匀的澄清溶液。在50℃将可可脂预熔化,同时使用机械搅拌器搅拌。然后使用均化器以3500RPM的均化器速度(均化器,Hsiang Tai Machinery Industry,型号:HG-300,最大速度-26000rpm)将所得到的辛烯基琥珀酸淀粉酯溶液和熔化的CB均化到HPS的5%w/w溶液中持续90秒。然后将所得到的分散体冷却至32℃-36℃,并且保持搅拌持续另外20分钟,以允许聚合物完全溶解。
表4-基于不同比例的HPS:CB:辛烯基琥珀酸淀粉酯的不同膜制剂
T1-20%w/w的来自最终微胶囊的细菌。T2-10%w/w的来自最终微胶囊的细菌。
v)微胶囊化制备工艺
微胶囊化工艺从产生芯开始,随后是包衣工艺:
1)芯制备
通过湿法制粒方法制备芯。将粘合剂(例如,麦芽糖糊精)的水溶液喷雾在由细菌和填料组成的粉末混合物上,以使颗粒固结以形成团聚物。用于制备微胶囊的组分被总结在表5中。
表5.根据本发明的一种实施方案的微胶囊的组成
2)包衣工艺
通过将聚合物溶液直接喷雾到从先前阶段得到的芯上进行包衣。
芯制备和包衣工艺两者均在Innojet Ventilus 2.5(Romaco-Huttlin,Esteinen-Germany)进行。
层的厚度通过%重量增加(WG)表示,所述%重量增加(WG)根据以下等式相对于包衣工艺之前的初始基材重量在包衣工艺后获得:
其中Wd和W0分别是包衣工艺之后和之前基材的重量,并且WG是重量增加。
表6-用于双歧杆菌制粒的参数
包衣工艺参数 | 数据 |
入口温度(℃) | 40-42 |
空气流量(m<sup>3</sup>/小时) | 32-40 |
喷雾速率(g/min) | 3.8-4.2 |
产品温度(℃) | 38-40 |
上部喷雾压力(巴) | 1.85-1.9 |
支持空气压力(巴) | 0.3 |
表7.用于双歧杆菌颗粒剂包衣的参数
vi)干燥失重(LOD)测试
在包衣工艺期间,以一定时间(每4%的重量增加),取2克的微胶囊进行LOD测试(LOD装置(MB-50-1-250,MRC))。
vii)稳定性测试。
1)室内条件:
将未包衣的双歧杆菌和微胶囊化的双歧杆菌暴露于室内条件(可变的温度和水分),并且每周取样以进行微生物学测试,持续6个月的时间段。
2)0.795Aw的水活度:
将未包衣的双歧杆菌和微胶囊化的双歧杆菌暴露于0.795Aw的条件(通过在干燥器的底部中具有0.795aw溶液的干燥器进行使用),并且每2天取样以进行微生物学测试,持续2周。
3)0.612Aw的水活度:
将未包衣的双歧杆菌和微胶囊化的双歧杆菌暴露于0.612Aw的条件(通过在干燥器的底部中具有0.795aw溶液的干燥器进行使用),并且每2天取样以进行微生物学测试,持续数周。
4)水蒸气透过率(WVTR)测试
本测试的构思是基于指定条件下每单位时间透过单位面积的测试膜样本的水蒸气的量的测量。水蒸气透过率被表示为克/平方米,24h[克/(m2,24h)]。配备有电解检测传感器的具有10cm2测量面积的Versaperm MkV数字WVTR仪表(Versaperm Ltd.,Maidenhead,UK)被用于测量不同膜的WVTR。测试在室温、100%湿度进行持续24h。该方法基于ISO15106e3:2003。简而言之,将测试样本插入两个不同的室之间:干燥室和受控湿度室。样本的干燥侧被干燥的载气流扫过,并且从受控湿度室渗透通过样本的水蒸气被载气携带到电解池中。该池包含两个螺旋丝电极,所述螺旋丝电极定量地吸收由载气携带的水蒸气并且通过向电极施加的D.C.电压将水蒸气电解地分解成氢气和氧气。每单位时间渗透通过样本并且分解的水分的质量由所需的电解电流计算。
viii)WVTR测试结果。
表8.1.基于不同比例的HPS:CB:辛烯基琥珀酸淀粉酯的不同膜制剂的WVTR结果
表8.2.基于不同比例的HPC-L(羟丙基纤维素):CB:辛烯基琥珀酸淀粉酯的不同膜制剂的WVTR结果
xi)稳定性测试结果-
1)生产工艺(基于制粒-芯形成期间粘合剂的水溶液的微胶囊化工艺)期间的稳定性
微生物学测试结果表明,尽管细菌的高敏感性,但在微胶囊化工艺期间细菌的数量没有减少并且保持与工艺开始时相同(以1.5*1011CFU/g双歧杆菌开始工艺,并且以1.55*1011CFU/g双歧杆菌完成)-以20%重量增加(非常重大的成就)。
表9呈现了LGG和另一种鼠李糖乳杆菌菌株在微胶囊化工艺(基于芯形成工艺期间粘合剂的水溶液)期间的稳定性结果。
表9.LGG在其微胶囊化工艺期间的稳定性(存活力)
*包衣配方:HPS:可可脂:辛烯基琥珀酸淀粉酯X02
2)随时间的持续稳定性
将按原样的微胶囊化细菌的颗粒[裸露的(未包装的)]暴露于室温的空气(20-22℃,≈35%-45%RH),并且在不同时间点取样进行计数测试,以确定CFU/g细菌。将结果与保持在相同条件下的按原样的纯双歧杆菌(未微胶囊化或未保护的细菌)进行比较。持续长达180天的结果被总结在表10.1中。
基于结果,可以清楚地注意到,按原样的双歧杆菌(未保护的细菌)在仅三周之后 损失4-5个对数,并且随着时间的推移保持几乎不变。值得注意的是,双歧杆菌粉末,作为细菌彼此附接的结果,随着时间的推移在表面产生看起来坚硬(rigid and hard)的层,这表现为颜色的急剧变化(从灰白色到黄色,并且然后到浅棕色)和触感的急剧变化。据信,这一新层负责保护细菌,并且随着时间的推移减弱对数的减少。当对数在约三周之后保持不变(10^6)时,这一点可能是对数的稳定化的主要原因。
还可以看到,对于一些特定的微胶囊化制剂,细菌被完全稳定化,在约13周之后看到仅一个对数损失。这一事实指示微胶囊化制剂确实提供所需的随时间的防湿气保护。
表10.1总结了计数测试的结果,该计数测试针对使用不同制剂的微胶囊化的细菌和保持裸露的(未包装的)纯乳双歧杆菌(双歧杆菌)两者在室温和≈35%-45%RH持续不同的持续时间来完成。
4)随时间的水含量测量
还使用干燥失重(LOD)方法随时间测量保持在进行持续稳定性测试的相同的条件的与纯细菌相比的具有某种制剂的微胶囊化的细菌的水含量。注意,水含量的任何增加都可以指示由粉末发生的水吸收,并且因此指示差的屏障能力。相比之下,LOD值无变化可以意味着良好的防湿气保护。
对于BB-12,水含量的结果被总结在表11中,并且图解地图示在图1中。
表11.1:与原样的双歧杆菌相比的保持在室温、≈35%-45%RH的微胶囊化的双歧杆菌随时间测量的水含量(湿气吸收)。
现在参考图1,图1描绘了保持在进行持续稳定性测试的相同条件的与纯细菌相比的具有某种制剂的微胶囊化的细菌的水含量,该水含量还使用干燥失重(LOD)方法随时间进行测量。
如图1中示出的,微胶囊化制剂提供针对水分吸收的适当屏障,并且因此随着时间的推移,没有微胶囊化的双歧杆菌的水含量的显著增加可以被观察到。相比之下,未保护的细菌在暴露于空气24小时之后,吸收约114%的水分,这些水分随时间的推移保持几乎不变。
对未保护的LGG(原样的LGG)和微胶囊化的LGG两者进行相同的实验,并且结果在表11.2中展示。
表11.2-与原样的LGG相比的保持在室温、≈35%-45%RH的微胶囊化的LGG所测量的水含量(湿气吸收)。
虽然本发明已经根据一些具体的实例进行了描述,但是许多修改和变化是可能的。因此,应理解,在所附权利要求的范围内,本发明可以以除如具体描述之外的方式被实现。
实施例2-芯和包衣组合物实施方案-(基于熔化的芯形成)
通过熔化制粒方法制备芯。将粘合剂(例如,可可脂)的熔化的液体喷雾在由细菌和填料组成的粉末混合物上,以使颗粒固结以形成团聚物。用于制备微胶囊的组分被总结在表12中。
表12.根据本发明的一种实施方案的微胶囊的组成
表13-用于鼠李糖乳杆菌熔化制粒的参数
表14.用于鼠李糖乳杆菌颗粒剂包衣的参数
包衣工艺参数 | 数据 |
入口温度(℃) | 34-40 |
空气流量(m<sup>3</sup>/小时) | 38-60 |
喷雾速率(g/min) | 1.8-2.2 |
产品温度(℃) | 34-39 |
上部喷雾压力(巴) | 2.45-2.5 |
生产工艺期间的稳定性
获取样品进行计数测试,以确定细菌(鼠李糖乳杆菌)在微胶囊化工艺期间的稳定性。结果被总结在表15中。
表15-鼠李糖乳杆菌在其使用熔化制粒工艺的微胶囊化工艺期间的稳定性(存活力)。
*包衣配方:HPS:可可脂:辛烯基琥珀酸淀粉酯X02
**包衣配方:HPS:硬脂酸:辛烯基琥珀酸淀粉酯X02
虽然本发明已经根据一些具体的实施例进行了描述,但是许多修改和变化是可能的。因此,应理解,在所附权利要求的范围内,本发明可以以除如具体描述之外的方式被实现。
Claims (10)
1.一种益生菌微胶囊,所述益生菌微胶囊包括:
芯,所述芯包含益生菌微生物;以及
包衣层,所述包衣层包含混合固体分散体,所述混合固体分散体包含均匀地分散在水溶性成膜聚合物和可食用介质内的可食用脂肪分子,其中所述可食用介质是辛烯基琥珀酸淀粉酯。
2.根据权利要求1所述的益生菌微胶囊,其中所述水溶性成膜聚合物是羟丙基淀粉。
3.根据权利要求2所述的益生菌微胶囊,其中所述益生菌微生物包括双歧杆菌。
4.根据权利要求3所述的益生菌微胶囊,其中所述可食用脂肪分子选自包括以下的组:月桂酸、肉豆蔻酸、棕榈酸、棕榈酸酯、棕榈油酸酯、羟基棕榈酸酯、花生酸、油酸、硬脂酸、硬脂酸钠、硬脂酸钙、硬脂酸镁、羟基二十八醇羟基硬脂酸酯、长链的油酸酯、脂肪酸的酯、脂肪醇、酯化的脂肪二醇、羟基化的脂肪酸、氢化脂肪酸(饱和或部分饱和的脂肪酸)、部分氢化大豆油、部分氢化棉籽油、脂肪族醇、磷脂质、卵磷脂、磷脂酰胆碱、脂肪酸的三酯、椰子油、氢化椰子油、可可脂;棕榈油;脂肪酸共晶体;甘油单酯和甘油二酯、泊洛沙姆、聚乙二醇和聚酯的嵌段共聚物或其组合。
5.根据权利要求4所述的益生菌微胶囊,其中所述可食用脂肪分子是可可脂。
6.根据权利要求4所述的益生菌微胶囊,其中所述可食用脂肪分子是硬脂酸。
7.根据权利要求1所述的益生菌微胶囊,其中所述混合固体分散体是单一混合固体分散体。
8.一种用于制备微胶囊的方法,所述方法包括:
制备包含双歧杆菌的微胶囊芯;
制备包含低水蒸气透过率(WVTR)值的至少一层包衣,所述至少一层包衣包含羟丙基淀粉(HPS)、可可脂(CB)和辛烯基琥珀酸淀粉酯;以及
用所述至少一层包衣包被所述芯。
9.根据权利要求8所述的方法,其中制备至少一层包衣包括:
通过将羟丙基淀粉(HPS)添加到加热的蒸馏水(85-90℃)中来制备HPS的5%w/w溶液;
通过将辛烯基琥珀酸淀粉酯(SOS)添加到加热的蒸馏水中并且继续地搅拌直到获得均匀的澄清溶液来制备SOS的溶液;
在使用机械搅拌器搅拌的同时预熔化可可脂(CB),以提供熔化的CB;以及
使用均化器将所述SOS溶液和所述熔化的CB均化到所述HPS的5%w/w溶液中。
10.根据权利要求9所述的方法,其中预熔化所述可可脂(CB)在50℃进行。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862660388P | 2018-04-20 | 2018-04-20 | |
US62/660,388 | 2018-04-20 | ||
PCT/IL2019/050454 WO2019202604A1 (en) | 2018-04-20 | 2019-04-20 | Moisture resistant probiotic granule and methods of producing the same |
Publications (1)
Publication Number | Publication Date |
---|---|
CN112292118A true CN112292118A (zh) | 2021-01-29 |
Family
ID=68238844
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201980041815.5A Pending CN112292118A (zh) | 2018-04-20 | 2019-04-20 | 耐湿性益生菌颗粒剂及其产生方法 |
Country Status (11)
Country | Link |
---|---|
US (1) | US20210186887A1 (zh) |
EP (1) | EP3781137A4 (zh) |
JP (1) | JP2021521249A (zh) |
KR (1) | KR20210003138A (zh) |
CN (1) | CN112292118A (zh) |
AU (1) | AU2019255435A1 (zh) |
BR (1) | BR112020021458A2 (zh) |
CA (1) | CA3097489A1 (zh) |
EA (1) | EA202092347A1 (zh) |
IL (1) | IL278101A (zh) |
WO (1) | WO2019202604A1 (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022090474A1 (en) * | 2020-10-29 | 2022-05-05 | Deerland Probiotics & Enzymes A/S | Microencapsulated microbial composition |
US20240115509A1 (en) * | 2021-02-11 | 2024-04-11 | Amd Pharma Ltd | A probiotic granule having a unified stabilizing coating and a method for the production thereof |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998015192A1 (en) * | 1996-10-09 | 1998-04-16 | Givaudan-Roure (International) S.A. | Process for preparing beads as food additive |
CN1545936A (zh) * | 2003-12-01 | 2004-11-17 | 上海交大昂立股份有限公司 | 一种含有活性益生菌的食用组合物及其制备方法 |
CN1613455A (zh) * | 2003-11-04 | 2005-05-11 | 北京东方百信生物技术有限公司 | 靶向益生菌微胶囊及其制备方法 |
US20050153018A1 (en) * | 2002-03-12 | 2005-07-14 | Nestec S.A. | Probiotic delivery system |
US20050266069A1 (en) * | 2002-09-06 | 2005-12-01 | Simmons Donald L | Stable probiotic microsphere compositions and their methods of preparation |
WO2014078912A1 (en) * | 2012-11-26 | 2014-05-30 | Progel Pty Ltd | Coating composition |
WO2017145143A1 (en) * | 2016-02-28 | 2017-08-31 | Degama Berrier Ltd. | A film composition and methods for producing the same |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2648528B1 (en) * | 2010-12-06 | 2016-07-20 | Degama Berrier Ltd. | Composition and method for improving stability and extending shelf life of probiotic bacteria and food products thereof |
CN103687496A (zh) * | 2011-06-07 | 2014-03-26 | Spai集团有限公司 | 用于改善敏感性食品添加剂及其食品产品的稳定性并且延长其货架期的组合物和方法 |
PT2986131T (pt) * | 2013-04-19 | 2020-10-08 | Degama Smart Ltd | Grânulos com bactérias probióticas resistentes ao calor e à humidade |
PL225613B1 (pl) * | 2013-10-08 | 2017-04-28 | Zachodniopomorski Univ Tech W Szczecinie | Sposób wytwarzania prozdrowotnego produktu spożywczego |
-
2019
- 2019-04-20 JP JP2020558517A patent/JP2021521249A/ja active Pending
- 2019-04-20 US US17/048,614 patent/US20210186887A1/en not_active Abandoned
- 2019-04-20 CA CA3097489A patent/CA3097489A1/en not_active Abandoned
- 2019-04-20 EP EP19787939.8A patent/EP3781137A4/en not_active Withdrawn
- 2019-04-20 AU AU2019255435A patent/AU2019255435A1/en not_active Abandoned
- 2019-04-20 KR KR1020207032066A patent/KR20210003138A/ko unknown
- 2019-04-20 CN CN201980041815.5A patent/CN112292118A/zh active Pending
- 2019-04-20 WO PCT/IL2019/050454 patent/WO2019202604A1/en active Application Filing
- 2019-04-20 EA EA202092347A patent/EA202092347A1/ru unknown
- 2019-04-20 BR BR112020021458-2A patent/BR112020021458A2/pt not_active IP Right Cessation
-
2020
- 2020-10-16 IL IL278101A patent/IL278101A/en unknown
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998015192A1 (en) * | 1996-10-09 | 1998-04-16 | Givaudan-Roure (International) S.A. | Process for preparing beads as food additive |
US20050153018A1 (en) * | 2002-03-12 | 2005-07-14 | Nestec S.A. | Probiotic delivery system |
US20050266069A1 (en) * | 2002-09-06 | 2005-12-01 | Simmons Donald L | Stable probiotic microsphere compositions and their methods of preparation |
CN1613455A (zh) * | 2003-11-04 | 2005-05-11 | 北京东方百信生物技术有限公司 | 靶向益生菌微胶囊及其制备方法 |
CN1545936A (zh) * | 2003-12-01 | 2004-11-17 | 上海交大昂立股份有限公司 | 一种含有活性益生菌的食用组合物及其制备方法 |
WO2014078912A1 (en) * | 2012-11-26 | 2014-05-30 | Progel Pty Ltd | Coating composition |
WO2017145143A1 (en) * | 2016-02-28 | 2017-08-31 | Degama Berrier Ltd. | A film composition and methods for producing the same |
Non-Patent Citations (1)
Title |
---|
于乐军等: "益生菌微胶囊化壁材的研究进展", 《现代生物医学进展》 * |
Also Published As
Publication number | Publication date |
---|---|
US20210186887A1 (en) | 2021-06-24 |
BR112020021458A2 (pt) | 2021-01-19 |
EP3781137A4 (en) | 2022-01-05 |
AU2019255435A1 (en) | 2020-11-26 |
EP3781137A1 (en) | 2021-02-24 |
KR20210003138A (ko) | 2021-01-11 |
IL278101A (en) | 2020-11-30 |
JP2021521249A (ja) | 2021-08-26 |
WO2019202604A1 (en) | 2019-10-24 |
CA3097489A1 (en) | 2019-10-24 |
EA202092347A1 (ru) | 2021-02-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2451300B2 (en) | Heat resistant probiotic compositions and healthy food comprising them | |
Zanjani et al. | Microencapsulation of Lactobacillus casei with calcium alginate-resistant starch and evaluation of survival and sensory properties in cream-filled cake | |
EP2868206B1 (en) | Microparticles for the encapsulation of probiotics, preparation and uses thereof | |
US7122370B2 (en) | Formulations to increase in vivo survival of probiotic bacteria and extend their shelf-life | |
Liu et al. | Incorporation of polysaccharides into sodium caseinate-low melting point fat microparticles improves probiotic bacterial survival during simulated gastrointestinal digestion and storage | |
AU2016365214B2 (en) | Stable dry compositions having no or little sugars | |
KR102557219B1 (ko) | 박테리아 조성물 | |
Damodharan et al. | Co-encapsulation of lactic acid bacteria and prebiotic with alginate-fenugreek gum-locust bean gum matrix: Viability of encapsulated bacteria under simulated gastrointestinal condition and during storage time | |
Barajas-Álvarez et al. | Microencapsulation of Lactobacillus rhamnosus HN001 by spray drying and its evaluation under gastrointestinal and storage conditions | |
EP2104434A1 (en) | Probiotic compositions and methods of making same | |
EP1885207A1 (en) | Compositions for enteral application of microorganisms | |
Sogut et al. | Whey protein isolate-and carrageenan-based edible films as carriers of different probiotic bacteria | |
Park et al. | Formulation and in vivo evaluation of probiotics-encapsulated pellets with hydroxypropyl methylcellulose acetate succinate (HPMCAS) | |
CN112292118A (zh) | 耐湿性益生菌颗粒剂及其产生方法 | |
CN116096856A (zh) | 利用辛烯基琥珀酸酐淀粉-壳聚糖复合团聚体微囊化微生物培养物 | |
Pyar et al. | Enteric coating of granules containing the probiotic Lactobacillus acidophilus | |
Harel et al. | Protection and delivery of probiotics for use in foods | |
KR102483912B1 (ko) | 연질캡슐형 건강기능식품의 제조방법 | |
CA2330390C (en) | Sugar coated tablets | |
US20210401760A1 (en) | Composite Coating for an Active Agent | |
KR102515677B1 (ko) | 리토탐니온으로 코팅되어 장 건강 및 유해균 억제 능력이 향상된 유산균을 포함하는 조성물 | |
WO2022090474A1 (en) | Microencapsulated microbial composition | |
Mandal et al. | Diversification of probiotics through encapsulation technology | |
WO2023094653A1 (en) | Fat and wax microencapsulated ambient stable bacteria and probiotics | |
CN116270523A (zh) | 一种耐酸的口服双层胶囊及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210129 |
|
WD01 | Invention patent application deemed withdrawn after publication |