CN101069677A - Pullulan polysaccharide hollow hard capsule and manufacturing method thereof - Google Patents
Pullulan polysaccharide hollow hard capsule and manufacturing method thereof Download PDFInfo
- Publication number
- CN101069677A CN101069677A CNA200710028704XA CN200710028704A CN101069677A CN 101069677 A CN101069677 A CN 101069677A CN A200710028704X A CNA200710028704X A CN A200710028704XA CN 200710028704 A CN200710028704 A CN 200710028704A CN 101069677 A CN101069677 A CN 101069677A
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- CN
- China
- Prior art keywords
- hard capsule
- capsule
- pulullan polysaccharide
- empty hard
- pulullan
- 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
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- 239000007902 hard capsule Substances 0.000 title claims abstract description 29
- 239000004373 Pullulan Substances 0.000 title claims abstract description 7
- 229920001218 Pullulan Polymers 0.000 title claims abstract description 7
- 235000019423 pullulan Nutrition 0.000 title claims abstract description 7
- 150000004676 glycans Chemical class 0.000 title claims description 38
- 229920001282 polysaccharide Polymers 0.000 title claims description 38
- 239000005017 polysaccharide Substances 0.000 title claims description 38
- 238000004519 manufacturing process Methods 0.000 title claims description 15
- 239000002775 capsule Substances 0.000 claims abstract description 36
- 239000007788 liquid Substances 0.000 claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 claims abstract description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000000499 gel Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 238000005189 flocculation Methods 0.000 claims description 9
- 230000016615 flocculation Effects 0.000 claims description 9
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000080 wetting agent Substances 0.000 claims description 8
- 239000003292 glue Substances 0.000 claims description 7
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 6
- 238000007598 dipping method Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 6
- 239000000679 carrageenan Substances 0.000 claims description 5
- 229920001525 carrageenan Polymers 0.000 claims description 5
- 229940113118 carrageenan Drugs 0.000 claims description 5
- 238000000855 fermentation Methods 0.000 claims description 5
- 230000004151 fermentation Effects 0.000 claims description 5
- 229920000053 polysorbate 80 Polymers 0.000 claims description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- 235000010418 carrageenan Nutrition 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 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 claims description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 3
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 3
- 229920001817 Agar Polymers 0.000 claims description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 3
- 239000008272 agar Substances 0.000 claims description 3
- 235000010419 agar Nutrition 0.000 claims description 3
- 239000001110 calcium chloride Substances 0.000 claims description 3
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 3
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 3
- 235000010987 pectin Nutrition 0.000 claims description 3
- 239000001814 pectin Substances 0.000 claims description 3
- 229920001277 pectin Polymers 0.000 claims description 3
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 239000001103 potassium chloride Substances 0.000 claims description 3
- 235000011164 potassium chloride Nutrition 0.000 claims description 3
- 239000001508 potassium citrate Substances 0.000 claims description 3
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 3
- 235000011082 potassium citrates Nutrition 0.000 claims description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
- 235000011009 potassium phosphates Nutrition 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- 235000011148 calcium chloride Nutrition 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229940008099 dimethicone Drugs 0.000 claims description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 2
- 238000004043 dyeing Methods 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 239000000576 food coloring agent Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 229960002635 potassium citrate Drugs 0.000 claims description 2
- 239000004408 titanium dioxide Substances 0.000 claims description 2
- 206010013786 Dry skin Diseases 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 229920002472 Starch Polymers 0.000 abstract description 11
- 229920002678 cellulose Polymers 0.000 abstract description 8
- 239000001913 cellulose Substances 0.000 abstract description 8
- 239000000463 material Substances 0.000 abstract description 8
- 239000008107 starch Substances 0.000 abstract description 4
- 235000019698 starch Nutrition 0.000 abstract description 4
- 230000007062 hydrolysis Effects 0.000 abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 230000004888 barrier function Effects 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract description 2
- 239000000701 coagulant Substances 0.000 abstract 1
- 239000007903 gelatin capsule Substances 0.000 abstract 1
- 239000003349 gelling agent Substances 0.000 abstract 1
- 239000003906 humectant Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 229920000159 gelatin Polymers 0.000 description 10
- 235000019322 gelatine Nutrition 0.000 description 10
- 241000196324 Embryophyta Species 0.000 description 9
- 235000019890 Amylum Nutrition 0.000 description 7
- 238000010612 desalination reaction Methods 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 208000005156 Dehydration Diseases 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 6
- 238000006297 dehydration reaction Methods 0.000 description 6
- 239000004014 plasticizer Substances 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 5
- 239000001828 Gelatine Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000011505 plaster Substances 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 4
- -1 hydroxypropyl Chemical group 0.000 description 4
- 238000009740 moulding (composite fabrication) Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000011343 solid material Substances 0.000 description 4
- 238000005520 cutting process Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 235000011069 sorbitan monooleate Nutrition 0.000 description 3
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- DBTMGCOVALSLOR-UHFFFAOYSA-N 32-alpha-galactosyl-3-alpha-galactosyl-galactose Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(OC2C(C(CO)OC(O)C2O)O)OC(CO)C1O DBTMGCOVALSLOR-UHFFFAOYSA-N 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 2
- RXVWSYJTUUKTEA-UHFFFAOYSA-N D-maltotriose Natural products OC1C(O)C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C1OC1C(O)C(O)C(O)C(CO)O1 RXVWSYJTUUKTEA-UHFFFAOYSA-N 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 2
- 229920002494 Zein Polymers 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000011344 liquid material Substances 0.000 description 2
- FYGDTMLNYKFZSV-UHFFFAOYSA-N mannotriose Natural products OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(OC2C(OC(O)C(O)C2O)CO)C(O)C1O FYGDTMLNYKFZSV-UHFFFAOYSA-N 0.000 description 2
- 239000003595 mist Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 235000019426 modified starch Nutrition 0.000 description 2
- 239000003605 opacifier Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005019 zein Substances 0.000 description 2
- 229940093612 zein Drugs 0.000 description 2
- FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside 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]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 0.000 description 2
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose 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
- 108010082495 Dietary Plant Proteins Proteins 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
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 241000206672 Gelidium Species 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
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 244000017020 Ipomoea batatas Species 0.000 description 1
- 235000002678 Ipomoea batatas Nutrition 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 229920002752 Konjac Polymers 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000195474 Sargassum Species 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 108010073771 Soybean Proteins Proteins 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
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 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
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 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
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 108010059642 isinglass Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052627 muscovite Inorganic materials 0.000 description 1
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical class C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 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
- 238000007493 shaping process Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a hollow hard capsule and a preparation method thereof, which is prepared by taking pullulan as a main material and matching with gelling agent, coagulant aid, surfactant, humectant and the like. The hollow hard capsule prepared by the invention has higher gas barrier property and impact strength, good quality stability, difficult friability, stable disintegration index and difficult hydrolysis, does not fog and yellow on the surface after being placed for a long time, is superior to a plant starch capsule or a cellulose derivative capsule in replacing a gelatin capsule, can contain solid, oily liquid, semisolid and paste materials, and has wide market prospect and practical value.
Description
Technical field
The present invention relates to be used for the empty hard capsule and the manufacture method thereof of splendid attire medicine or food.
Background technology
Empty hard capsule is widely used as medicine or packaging for foodstuff carrier, mainly contains three classes at present:
One class is widely used gelatine capsule, the gelatin that skin, bone extracted by animal cooperates some plasticizers, opacifier, pigment to make, but because the influence of Animal diseases such as bovine spongiform encephalopathy, foot and mouth disease in recent years, cause the fear of people to animal product, think that there is potential safety hazard in animal proteinum, some religion to animal product also one to being resisted.In addition, gelatine capsule is relatively more responsive to the variation of temperature humidity, in not hydrolysis easily at that time of temperature humidity, and degeneration, fragmentation, therefore, gelatine capsule constantly is subjected to the refusal of each side.
Another kind of is the plant amylum capsule, cooperates certain plasticizer etc. to make by plant amylum or starch derivatives.As disclosed starch Capsules of Chinese patent prospectus CN1483393A and production technology thereof, make by components such as plant amylum or starch derivatives, plasticizer, water.The disclosed capsule of CN1623529A is made up of potato starch, carrageenan, surfactant, plasticizer.CN1739488A discloses with Konjaku plucosidopolyose through the acid hydrolysis oxidative modification, with modification or unmodified vegetable protein (comprising soybean protein, zein, wheat protein, zein), in animal gelatin or the isinglass one or both are compound to be main component, and auxiliary element such as glycerol, dodecane sulfonate is made Capsules.The disclosed Capsules of CN1895234A is with amylose, and glycerol is that primary raw material makes.CN1903157A is open to be that raw material is made the gastric solubleness Capsules with Sargassum polysaccharides glue.Open extract and the glycerol etc. by amylose or soluble starch such as corn, Rhizoma Solani tuber osi, Maninot esculenta crantz., Ipomoea batatas Lam., Rhizoma Dioscoreae of CN1931145A is made plant hollow capsule.The plant amylum capsule is to develop in recent years, and in order to the new product of alternative gelatine capsule, but technology is ripe not to the utmost, and the plant amylum capsule is crisp, and the product friability is still defective, and in addition, the plant amylum capsule can not be used for the carrying liquid material.
Also having a class is to be the hard capsule that primary raw material is made with the water-soluble cellulose derivative.Open as Chinese patent prospectus CN1418081A, CN1329478A by gelatin or the capsule made as the water-soluble cellulose derivative of hydroxypropyl emthylcellulose, plasticizer etc.Open carboxymethylcellulose calcium of CN1202102A or cross-linking sodium carboxymethyl cellulose, the capsule that gelatinized starch and crospovidone etc. is made.The open plant hard capsule of making by hydrophilic gel, water-soluble cellulose, flocculation aid of CN1292261A.The open capsule of making by gelatin or water-soluble cellulose derivative such as hydroxyprolyl-methylcellulose, plasticizer etc. of CN1646369A.CN1745745A is open by the K-carrageenan, the Capsules that cellulose derivative such as hypromellose, ethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, alcohols are made.Up to the present, be that the Capsules quality made of primary raw material is still unstable with the water-soluble cellulose derivative, particularly in gastrointestinal disintegrate instability, and capsule shells is separated out chemical substance behind the certain hour, and mist is sent out on the surface, yellowing occurs, and face shaping is relatively poor.
Summary of the invention
The objective of the invention is the defective that exists at above-mentioned all kinds of capsules, provide that a kind of disintegrate index is stable, friability is better, smooth surface, and empty hard capsule that can the carrying liquid material.
For achieving the above object, the present invention adopts pulullan polysaccharide as material of main part, comprises following component and percentage by weight: pulullan polysaccharide 58～96%, gel 0～10%, flocculation aid 0～2%, surfactant 0～5%, wetting agent 0～5%, surplus are aequum moisture; Described gel is one or more in carrageenan, agar, pectin, the sodium alginate; Described flocculation aid is one or more in potassium chloride, calcium chloride, potassium phosphate, the potassium citrate; Described surperficial voltinism agent is one or more in dodecyl sodium sulfate, Tween 80, the span; Described wetting agent is one or more in glycerol, dimethicone, the Oleum Ricini.
Pulullan polysaccharide English name pullulan of the present invention, Chinese also is translated into pulullan, pullulan, pullulan, general poly-polysaccharide, can be by glucidtemns, sucrose, or other saccharide direct fermentation produces, it is the extracellular polysaccharide of the mould generation of falx of sprouting, mainly with α-1, the 6-glycosidic bond constitutes the homotype polysaccharide in conjunction with maltose, and promptly glucose is pressed α-1, and the 4-glycosidic bond is combined into maltotriose, two ends are again with α-1, the 6-glycosidic bond is connected to become macromolecule polysaccharide so repeatedly with other maltotriose combination, α-1,4-glycosidic bond and α-1, the ratio of 6-glycosidic bond is 2: 1, the degree of polymerization 10～30000, molecular weight 2.0 * 10
3～5.0 * 10
6Dalton.Pulullan polysaccharide can be got with mode dehydrate such as spraying, fluid bed after sterilization, decolouring, desalination by the pulullan fermentation liquid, also can adopt organic solvent method to extract the dry thing that forms, method as Chinese patent prospectus CN1651467A introduction, after the sterilization of pulullan fermentation liquid, obtain with the drying precipitate after organic solvent decolouring, desalination and the dehydrations such as ethanol, isopropyl alcohol.The present invention can use molecular weight 2.0 * 10
3～5.0 * 10
6Pulullan polysaccharide, preferably mean molecule quantity 5.0 * 10
4～1.0 * 10
6Pulullan polysaccharide.The pulullan polysaccharide that can use mode dehydrate such as spraying, fluid bed to make, but preferably by the sedimentary dry thing of pulullan fermentation liquid after dehydration of organic solvent such as ethanol or isopropyl alcohol, decolouring and desalination.
Tween 80 of the present invention, English name Tweenum 80, chemical name: polyoxyethylene 20 sorbitan monooleate is the mixture of polyoxyethylene 20 sorbitan monooleate and the two sorbitan monooleates of fraction polyoxyethylene, main component molecular formula: C
64H
124O
26
Span of the present invention is a sorbitan fatty acid ester, and desirable span comprises: Arlacel-20 (sorbitan mono-laurate), Arlacel-40 (anhydrous sorbitol acid anhydride monopalmitate) Arlacel-60 (sorbitan monostearate), Arlacel-80 (sorbitan monooleate) or Arlacel-85 (sorbitan monooleate).
Aequum moisture of the present invention is from the hygroscopicity of component among the present invention, wherein pulullan polysaccharide, gel have more intense hygroscopicity, therefore the moisture that generally contains the balance water absorption in the finished product, variation according to ambient humidity, aequum moisture generally can account for gross weight 4～20%, select suitable humidity environment can make aequum moisture between 5～15%, this scope is that the present invention preferably stores and service condition.
Preferred ingredients of the present invention and percentage by weight are: pulullan polysaccharide 68～95%, and gel 1～8%, flocculation aid 0～2%, surfactant 0～2%, wetting agent 0～2%, surplus is an aequum moisture.
Be more preferably: pulullan polysaccharide 77～95%, gel 1～6.5%, flocculation aid 0.3～1%, surfactant 0.04～0.2%, wetting agent 0.04～0.2%, surplus is an aequum moisture.
The present invention can also contain 0.1～5% titanium dioxide makes product color occur as the food coloring of opacifier and dyeing amount.
The manufacture method of empty hard capsule of the present invention may further comprise the steps:
A. by said components and weight ratio, add weight ratio by pulullan polysaccharide and water and be 1: 1～10 pure water, be heated with stirring to 30～95 ℃, fully filter with 80～150 order defecators after the dissolving.
B. filtrate is after adjust gelatin concentration, removing bubble, on capsule manufacture equipment through dipping in glue, 20～60 ℃ of oven dry, the demoulding is cut edge, fit, check becomes empty hard capsule.
Above-mentioned steps A soaked 0.5～6 hour after also can be earlier pulullan polysaccharide being added pure water by 1: 1～10 weight ratio, was heated to 30～95 ℃ of dissolvings then, added described other component heated and stirred again and dissolved.
The weight ratio of above-mentioned pulullan polysaccharide and pure water is preferably 1: 6～and 9, the heating melting temperature is preferably to 60～90 ℃.
The empty hard capsule that the present invention makes is because the pulullan polysaccharide molecule is regular, the molecular weight excursion is little, and product quality is controlled easily, has higher gas barrier property and impact strength, quality stability is good, be difficult for crisp brokenly, the disintegrate index is stable, not facile hydrolysis, long-time placement surface is not sent out the mist jaundice, be better than plant amylum capsule or cellulose-derived composite capsule substituting on the gelatine capsule, can the splendid attire solid, oily liquids, semisolid and plaster material, extensive market prospects and practical value are arranged.
The specific embodiment
Embodiment 1
Be averaged molecular weight 200,000, by 10 kilograms of the pulullan polysaccharides that obtains after ethanol dehydration, decolouring and the desalination (containing 6wt% moisture), join in 65 kilograms of pure water, soaked 1 hour, be heated to 80 ℃ under stirring, after treating that pulullan polysaccharide all dissolves, add carrageenan 350 grams, dodecyl sodium sulfate 5 grams, glycerol 5 grams, add potassium chloride 75 grams after the dissolving again, filter with 100 order defecators after the uniform dissolution.
After removing bubble, on automatic capsule manufacture equipment through dipping in glue, 40 ℃ of drying formings, demouldings then.Through side cut, fit, check becomes transparent empty hard capsule.The empty hard capsule of making can be used as Capsules after tested, can the splendid attire solid material, and also can the fill oily liquids, semisolid or plaster material.
Embodiment 2
Be averaged molecular weight 300,000, by 10 kilograms of the pulullan polysaccharides that obtains after ethanol dehydration, decolouring and the desalination (containing 8wt% moisture), 200 gram pectin, 10 gram Arlacel-20s, 20 gram dimethicones and 40 gram potassium citrates, join in 70 kilograms of pure water, be heated to 90 ℃ under stirring, filter with 100 order defecators after the uniform dissolution.
After removing bubble, on automatic capsule manufacture equipment through dipping in glue, 40 ℃ of drying formings, the demoulding then, through cutting edge, fit, check becomes transparent empty hard capsule.The empty hard capsule of making can be used as Capsules after tested, can the splendid attire solid material, and also can the fill oily liquids, semisolid or plaster material.
Embodiment 3
Be averaged molecular weight 100,000, by 10 kilograms of the pulullan polysaccharides that obtains after ethanol dehydration, decolouring and the desalination (containing 8wt% moisture), join in 70 kilograms of pure water, stir down and be heated to 75 ℃, treat that pulullan polysaccharide all after the dissolving, adds 250 and restrains agar, 10 gram Tween 80s, 15 gram Oleum Ricini and 40 gram calcium chloride, 100 grams, 300 order titania powders, proper amount of edible coloring agent.Filter with 100 order defecators after the uniform dissolution.
After removing bubble, on automatic capsule manufacture equipment through dipping in glue, 40 ℃ of drying formings, the demoulding then, through cutting edge, fit, check becomes painted opaque empty hard capsule.The empty hard capsule of making can be used as Capsules after tested, can the splendid attire solid material, and also can the fill oily liquids, semisolid or plaster material.
Embodiment 4
Be averaged molecular weight 800,000, by 10 kilograms of the pulullan polysaccharides that obtains after ethanol dehydration, decolouring and the desalination (containing 8wt% moisture), join in 90 kilograms of pure water, stir down and be heated to 90 ℃, treat that pulullan polysaccharide all dissolves after, add sodium alginate 650 grams, dodecyl sodium sulfate 10 grams, glycerol 20 grams, the dissolving back adds potassium phosphate 100 grams, 100 grams, 300 order titania powders, the proper amount of edible coloring agent.Filter with 100 order defecators after the uniform dissolution.
After removing bubble, on automatic capsule manufacture equipment through dipping in glue, 40 ℃ of drying formings, the demoulding then, through cutting edge, fit, check becomes painted opaque empty hard capsule.The empty hard capsule of making can be used as Capsules after tested, can the splendid attire solid material, and also can the fill oily liquids, semisolid or plaster material.
Claims (10)
1. a pullulan polysaccharide hollow hard capasule is characterized in that, comprises following component and percentage by weight: pulullan polysaccharide 58～96%, and gel 0～10%, flocculation aid 0～2%, surfactant 0～5%, wetting agent 0～5%, surplus is an aequum moisture; Described gel is one or more in carrageenan, agar, pectin, the sodium alginate; Described flocculation aid is one or more in potassium chloride, calcium chloride, potassium phosphate, the potassium citrate; Described surperficial voltinism agent is one or more in dodecyl sodium sulfate, Tween 80, the span; Described wetting agent is one or more in glycerol, dimethicone, the Oleum Ricini.
2. according to the described empty hard capsule of claim 1, it is characterized in that described pulullan polysaccharide mean molecule quantity is 5.0 * 10
4～1.0 * 10
6
3. according to the described empty hard capsule of claim 1, it is characterized in that described pulullan polysaccharide is to adopt the organic solvent method precipitation to extract by the pulullan fermentation liquid to form.
4. according to the described empty hard capsule of claim 1, it is characterized in that, comprise following component and percentage by weight: pulullan polysaccharide 68～95%, gel 1～8%, flocculation aid 0～2%, surfactant 0～2%, wetting agent 0～2%, surplus are aequum moisture.
5. according to the described empty hard capsule of claim 4, it is characterized in that, comprise following component and percentage by weight: pulullan polysaccharide 77～95%, gel 1～6.5%, flocculation aid 0.3～1%, surfactant 0.04～0.2%, wetting agent 0.04～0.2%, surplus are aequum moisture.
6. according to the described empty hard capsule of claim 1, it is characterized in that, also contain the food coloring of 0.1～5% titanium dioxide and dyeing amount.
7. the manufacture method of the described empty hard capsule of the arbitrary claim of claim 1～6 is characterized in that, may further comprise the steps:
A. by described component of the arbitrary claim of claim 1～6 and weight ratio, add weight ratio by pulullan polysaccharide and water and be 1: 1～10 pure water, be heated with stirring to 30～95 ℃, fully filter with 80～150 order defecators after the dissolving.
B. filtrate is after adjust concentration, removing bubble, on capsule manufacture equipment through dipping in glue, 20～60 ℃ of dryings, the demoulding is cut edge, fit, check becomes empty hard capsule.
8. the manufacture method of the described empty hard capsule of claim 7 is characterized in that, in the described steps A, after pulullan polysaccharide adds pure water by 1: 1～10 weight ratio, soaked 0.5～6 hour, and be heated to 30～95 ℃ of dissolvings then, add described other component heated and stirred dissolving again.
9. the manufacture method of the described empty hard capsule of claim 7 is characterized in that, the weight ratio of described pulullan polysaccharide and pure water is 1: 6～9.
10. the manufacture method of the described empty hard capsule of claim 8 is characterized in that, described pulullan polysaccharide heating melting temperature is preferably to 60～90 ℃.
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|---|---|---|---|
| CNA200710028704XA CN101069677A (en) | 2007-06-15 | 2007-06-15 | Pullulan polysaccharide hollow hard capsule and manufacturing method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200710028704XA CN101069677A (en) | 2007-06-15 | 2007-06-15 | Pullulan polysaccharide hollow hard capsule and manufacturing method thereof |
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| Publication Number | Publication Date |
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| CN101069677A true CN101069677A (en) | 2007-11-14 |
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| CNA200710028704XA Pending CN101069677A (en) | 2007-06-15 | 2007-06-15 | Pullulan polysaccharide hollow hard capsule and manufacturing method thereof |
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