CN110354106A - A kind of film rapidly-soluble in the oral cavity and preparation method thereof - Google Patents
A kind of film rapidly-soluble in the oral cavity and preparation method thereof Download PDFInfo
- Publication number
- CN110354106A CN110354106A CN201910774122.9A CN201910774122A CN110354106A CN 110354106 A CN110354106 A CN 110354106A CN 201910774122 A CN201910774122 A CN 201910774122A CN 110354106 A CN110354106 A CN 110354106A
- Authority
- CN
- China
- Prior art keywords
- film
- soluble
- oral cavity
- weight
- rapidly
- 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.)
- Granted
Links
- 210000000214 mouth Anatomy 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000004014 plasticizer Substances 0.000 claims abstract description 21
- 239000000463 material Substances 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 15
- 239000008186 active pharmaceutical agent Substances 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 81
- -1 hydroxymethyl-propyl Chemical group 0.000 claims description 59
- 229920002678 cellulose Polymers 0.000 claims description 56
- 239000001913 cellulose Substances 0.000 claims description 56
- 239000005913 Maltodextrin Substances 0.000 claims description 35
- 229920002774 Maltodextrin Polymers 0.000 claims description 35
- 229940035034 maltodextrin Drugs 0.000 claims description 35
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 28
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000006185 dispersion Substances 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 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 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229960004063 propylene glycol Drugs 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000002604 ultrasonography Methods 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- 229920001661 Chitosan Polymers 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920002301 cellulose acetate Polymers 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 229940081735 acetylcellulose Drugs 0.000 claims 1
- 229940045110 chitosan Drugs 0.000 claims 1
- 229940014259 gelatin Drugs 0.000 claims 1
- 230000008901 benefit Effects 0.000 abstract description 10
- 210000002249 digestive system Anatomy 0.000 abstract description 4
- 238000002347 injection Methods 0.000 abstract description 4
- 239000007924 injection Substances 0.000 abstract description 4
- 238000010923 batch production Methods 0.000 abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 14
- 229920000881 Modified starch Polymers 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000013049 sediment Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000002218 hypoglycaemic effect Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 235000009508 confectionery Nutrition 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003292 glue Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229940037201 oris Drugs 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 229940127003 anti-diabetic drug Drugs 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-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
- 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 1
- 201000002451 Overnutrition Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 102100040918 Pro-glucagon Human genes 0.000 description 1
- 208000014139 Retinal vascular disease Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
- 241000254223 Syntexis Species 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229950009226 ciglitazone Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 102000056448 human GLP1R Human genes 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000020442 loss of weight Diseases 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960003365 mitiglinide Drugs 0.000 description 1
- WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 235000020823 overnutrition Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000837 restrainer Substances 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Zoology (AREA)
- Physiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of films rapidly-soluble in the oral cavity and preparation method thereof, the film includes following weight percent composition: 0.09~0.155 parts by weight of active pharmaceutical ingredient, 0.6~1 parts by weight of water soluble film-forming material, 0.15~0.3 parts by weight of plasticizer, 0~0.1 parts by weight of disintegrating agent.For the film compared with injection and oral agents, film has the advantages of capable of avoiding digestive system, quickly dissolving and absorb in the oral cavity.The film preparation method is simple, economical and practical and be easy to implement industrialization batch production.
Description
Technical field
The present invention relates to pelliculae pro cavo oris technical fields, and in particular to a kind of film rapidly-soluble in the oral cavity and its preparation
Method.
Background technique
With aging of population, urbanization and living-pattern preservation, the number of global diabetic over the past thirty years
Amount increases one times or more.Diabetes (diabetes mellitus, DM) are by inherent cause and the long-term phase interaction of environmental factor
With caused hypoinsulinism or defect is acted on, while being not suitable for the bidifly increased element disease with glucagon, with
Glucose level raising is biochemical character and more to drink, mostly food, diuresis, syntexis, out of strength etc. are disorderly for the metabolism of Clinical symptoms in blood
Random syndrome.Diabetes are a kind of common dysbolism diseases, i.e. blood glucose (glucose) is increased, then flowed away from urine,
So having sugar in urine.Specifically, with excessive intake total heat energy, fat, carbohydrate, few to move, overnutrition is related.If sick
Gesture control is bad, will cause complication in the future, such as heart disease, coronary heart disease, cerebrovascular disease, retinal vascular disease, the arteria renalis is hard
Change, limb artery hardening etc..
Diabetes are broadly divided into type 1 diabetes, diabetes B, gestational diabetes mellitus and other specific type diabetes.?
In diabetic, mainly based on type 1 diabetes, diabetes B, ratio shared by diabetes B is about 95%.According to
International Diabetes Federation investigation discovery, in 2017, the whole world nearly 4.51 hundred million people were influenced by diabetes B (T2DM),
It expects the number that 2045 are influenced by T2DM and is up to 6.93 hundred million.Diabetes B (T2DM) has genetic predisposition, is common in
The elderly, overweight people's disease incidence is high, and the course of disease is long and is easy to cause multiple complications, often can be with hypertension, dyslipidemia, artery
The diseases such as hardening.Insidious onset, in early days without any symptom, or it is only slight out of strength, thirsty, serum insulin level early stage is normal
Or increase, advanced stage is low.T2DM pathogenesis is to lead to insulin secretion reduction or insulin by islet beta cell function defect
Regulate and control the decline of glucose metabolism ability, i.e. it is main with hyperglycemia that sugar, rouge caused by insulin resistance, protein metabolism is abnormal
Metabolic-endocrine system disease of feature.
The hypoglycemic medicine of Modern medical therapy T2DM mainly includes biguanides, such as insoral, melbine；
Sulphonylurea, such as Glipizide, gliclazide, glibenclamide；Thiazolidinediones hypoglycemic medicine, such as Qu Gelie
Ketone, Rosiglitazone, Pioglitazone, Ciglitazone etc.；Meglitinide hypoglycemic medicine, such as Repaglinide, Nateglinide, Mitiglinide
Deng；Alpha-glucosidase restrainer antidiabetic drug, such as acarbose, voglibose；GLP-1 receptor stimulating agent antidiabetic drug, such as
Exenatide, Liraglutide, Suo Malu peptide etc..
Suo Malu peptide (Semaglutide) is to utilize people's glicentin-of yeast production by gene recombination technology
1 analog has 94% sequence homology with people GLP-1.The permanent mechanism of Suo Malu peptide is based on the modification to structure, rope
Horse Shandong peptide is revised as α-aminoacid at the 8th, for increasing stabilization, avoids being degraded by DPP-4 enzyme.In addition, passing through
Peptide chain the 26th lysine position is connected upper 18 carbocyclic aliphatic diacid side chain, enhanced affine with albumin by structural modification
Power increases the molecular weight of this product, avoids quickly removing and prevent metabolic degradation by kidney, extends Half-life in vivo.Relatively
In other several human glucagon-like-peptide-1 receptor stimulating agents (GLP-1RA), Suo Malu peptide is in hypoglycemic, loss of weight, cardiovascular system
System benefit and safety etc. show bigger advantage.
Currently, Suo Malu peptide should mainly include injection and it is oral, there are no Suo Malu peptide pelliculae pro cavo oris research.
Summary of the invention
The purpose of the present invention is to provide a kind of film rapidly-soluble in the oral cavity, the film and injection and oral agents
It compares, film has the advantages of capable of avoiding digestive system, quickly dissolving and absorb in the oral cavity.
In addition, the present invention also provides the preparation methods of above-mentioned film.
The present invention is achieved through the following technical solutions:
A kind of film rapidly-soluble in the oral cavity, including following parts by weight of component:
0.09~0.155 parts by weight of active pharmaceutical ingredient, 0.6~1 parts by weight of water soluble film-forming material, plasticizer 0.15~
0.3 parts by weight, 0~0.1 parts by weight of disintegrating agent.
Active pharmaceutical ingredient of the present invention specifically refers to the drug for treating diabetes B.
The present invention is by being mixed with film forming agent for active pharmaceutical ingredient and water soluble film-forming material, plasticizer and water, institute
Stating film is that physiology is subjected to film, discharges drug in the oral cavity, is absorbed and is entered in blood by oral mucosa, it
Advantage is that pharmaceutical preparation can avoid digestive system, and direct oral cavity mucous membrane or sublingual absorption can enter blood in a few minutes,
Play curative effect.Meanwhile film provided by the invention also has the advantage that small in size, thickness is thin, is convenient for carrying, clog-free pharynx
The danger of larynx is not necessarily to drinking-water；Fater disintegration, dissolution increase stability, release the drug rapidly；Mucosal drug delivery avoids first pass effect, intestines
Road remain less, adverse reaction；Mucoadhesive can cover bad smell.
In the present invention, the specific setting of active pharmaceutical ingredient content is that drug effect according to actual needs is matched, institute
The specific setting for stating the content of water soluble film-forming material and plasticizer is based on the folding resistance and disintegration time for considering film.It will
Each component of the invention is set as aforementioned proportion, the folding resistance of film and disintegration time can be controlled preferable range.
Further, the water soluble film-forming material include at least hydroxymethyl-propyl cellulose, maltodextrin, gelatin,
One of hyaluronic acid, chitosan, cellulose acetate.
Further, water soluble film-forming material is the mixture of hydroxymethyl-propyl cellulose and maltodextrin.
Applicant is found by experiment that:
Hydroxymethyl-propyl cellulose has good filming performance, forms a film transparent, smooth, uniform, but the softness of film
Performance is poor；The filming performance of maltodextrin is poor, and form a film breakage, is sticked on mold, can not normally demould.By methylol
Propyl cellulose and maltodextrin mixing are used as water soluble film-forming material, and the pelliculae pro cavo oris film clarity of preparation is preferable, flat
It is whole, uniform, and better softness.
Further, the weight ratio of hydroxymethyl-propyl cellulose and maltodextrin is 3:2~1:2.
Applicant is found by experiment that:
The weight ratio of hydroxymethyl-propyl cellulose and maltodextrin is affected to the folding resistance and disintegration time of film:
When the dosage of maltodextrin is fixed, as hydroxymethyl-propyl cellulose content reduces (hydroxymethylpropyl fiber
The weight ratio of element and maltodextrin reduces), folding decreases, and disintegration time reduces, while film also becomes more to glue；With
Hydroxymethyl-propyl cellulose content increases (increase of the weight ratio of hydroxymethyl-propyl cellulose and maltodextrin), and folding is dropped
Low, disintegration time reduces.
3:2~1:2 is set by the weight ratio of hydroxymethyl-propyl cellulose and maltodextrin, it can be by the viscosity of film
Control is in preferable range, and film has preferable folding resistance and disintegration time, the hydroxymethyl-propyl cellulose viscosity simultaneously
For 3~50cP.
Preferably, the weight ratio of hydroxymethyl-propyl cellulose and maltodextrin is set as 1:1, hydroxymethyl-propyl cellulose
Viscosity is 10~20cP.
Further, hydroxymethyl-propyl cellulose is the hydroxypropyl methyl cellulose of viscosity 15cP.
The hydroxypropyl methyl cellulose of viscosity 15cP compare other viscosity hydroxypropyl methyl cellulose, have preferably at
Film properties.
Further, plasticizer includes at least one of 1,2-PD, glycerol.
The preferably mixture of 1,2- propylene glycol and glycerol.
Applicant is found by experiment that:
Using glycerol as plasticizer, the appearance of film is poor, there is white particle precipitation.Either glycerol or 1,2- the third two
Alcohol, as film plasticizer increases, folding has obvious improvement, has a preferable folding using glycerol as plasticizer, but film
Disintegration time it is longer；Poor as the folding of plasticizer film using 1,2-PD, disintegrating property is preferable.
Further, when plasticizer is the mixture of 1,2-PD and glycerol, the weight of 1,2-PD and glycerol
Than for 0.5:1~2:1.
Applicant is found by experiment that: setting 0.5:1~2:1 for the weight ratio of 1,2- propylene glycol and glycerol can be simultaneously
Meet film it is resistance to roll well it is good with disintegrating property.
Preferably, the weight ratio of 1,2-PD and glycerol is 1:1.
Further, active pharmaceutical ingredient is Suo Malu peptide.
Further, disintegrating agent is pregelatinized starch.
A kind of preparation method of film rapidly-soluble in the oral cavity, comprising the following steps:
1), water soluble film-forming material is dissolved in the water, obtains aqueous solution；
2) plasticizer and disintegrating agent are added in aqueous solution under stirring, are uniformly mixing to obtain dispersion liquid；
3), active pharmaceutical ingredient is added in dispersion liquid and is stirred evenly；
4), ultrasound removes bubble, and solution is spread evenly across on polymeric material culture dish；
5), blast heating is dry, and heat drying temperature is 40~60 DEG C, and the demoulding of stemness release agent is cut into required size and obtains
To oral quick-dissolving film preparation.
Preparation method of the present invention not only simple process, economical and practical, and it is easy to implement industrialization batch production.
Compared with prior art, the present invention having the following advantages and benefits:
1, film of the present invention is compared with injection and oral agents, and film is with that can avoid digestive system, in oral cavity
In the advantages of quickly dissolving and absorb
2, the present invention is by optimizing water soluble film-forming material and plasticizer, including between concrete component and component
The optimization of proportion not only ensures that film has preferable appearance, meanwhile, there is preferable folding resistance and shorter disintegration time.
3, preparation method of the present invention not only simple process, economical and practical, and it is easy to implement industrialization batch production.
Detailed description of the invention
Attached drawing described herein is used to provide to further understand the embodiment of the present invention, constitutes one of the application
Point, do not constitute the restriction to the embodiment of the present invention.In the accompanying drawings:
Fig. 1 is the measuring mechanical property figure of film prepared by embodiment 5；
Fig. 2 is the content measuring chromatogram of film prepared by embodiment 5.
Specific embodiment
To make the objectives, technical solutions, and advantages of the present invention clearer, below with reference to embodiment and attached drawing, to this
Invention is described in further detail, and exemplary embodiment of the invention and its explanation for explaining only the invention, are not made
For limitation of the invention.
Embodiment 1:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.128g, hydroxymethyl-propyl cellulose 1g, 1,2-PD 0.15g, the hydroxymethylpropyl fiber
The viscosity of element is 15cP.
Embodiment 2:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.128g, maltodextrin 1g, 1,2-PD 0.15g, the hydroxymethyl-propyl cellulose glue
Degree is 15cP.
Embodiment 3:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.155g, maltodextrin 0.4g, hydroxymethyl-propyl cellulose 0.6g, glycerol 0.3g, pregelatinated form sediment
Powder 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 4:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.135g, maltodextrin 0.4g, hydroxymethyl-propyl cellulose 0.5g, glycerol 0.225g, pregelatinated
Starch 0.09g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 5:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.120g, maltodextrin 0.4g, hydroxymethyl-propyl cellulose 0.4g, glycerol 0.2g, pregelatinated form sediment
Powder 0.08g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 6:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.09g, maltodextrin 0.4g, hydroxymethyl-propyl cellulose 0.2g, glycerol 0.15g, pregelatinated form sediment
Powder 0.06g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 7:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, glycerol 0.15g, pregelatinated form sediment
Powder 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 8:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.144g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, glycerol 0.2g, pregelatinated form sediment
Powder 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 9:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.150g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, glycerol 0.25g, pregelatinated form sediment
Powder 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 10:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.15g, in advance
Gelling starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 11:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.144g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.2g, in advance
Gelling starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 12:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.150g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.25g, in advance
Gelling starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 13:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.05g are sweet
Oily 0.1g, pregelatinized starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 14:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.075 are sweet
Oil 0.075, pregelatinized starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 15:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.1g are sweet
Oily 0.05g, pregelatinized starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 16:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.075g,
Glycerol 0.075g, pregelatinized starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 15cP.
Embodiment 17:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.075g,
Glycerol 0.075g, pregelatinized starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 10cP.
Embodiment 18:
A kind of film rapidly-soluble in the oral cavity, is made of following parts by weight of component:
Suo Malu peptide 0.139g, maltodextrin 0.5g, hydroxymethyl-propyl cellulose 0.5g, 1,2-PD 0.075g,
Glycerol 0.075g, pregelatinized starch 0.1g, the viscosity of the hydroxymethyl-propyl cellulose are 20cP.
A kind of preparation method of the film as described in embodiment 1- embodiment 18, comprising the following steps:
1), water soluble film-forming material is dissolved in the water, obtains aqueous solution；
2) plasticizer and disintegrating agent are added in aqueous solution under stirring, are uniformly mixing to obtain dispersion liquid；
3), active pharmaceutical ingredient is added in dispersion liquid and is stirred evenly；
4), ultrasound removes bubble, and solution is spread evenly across on polymeric material culture dish；
5), blast heating is dry, and heat drying temperature is 40~60 DEG C, and the demoulding of stemness release agent is cut into 2 × 3cm2?
To oral quick-dissolving film preparation.
The film of Examples 1 to 2 is subjected to ocular estimate, as a result it is as shown in the table:
Table 1
The above result shows that hydroxymethyl-propyl cellulose has good filming performance, form a film transparent, smooth, uniform,
But the softness of film is poor, the filming performance of maltodextrin is poor, and form a film breakage, is sticked on mold, can not be normal
Demoulding.Therefore, it is preferable to prepare oral instant membrane effect for two kinds of compound film materials of hydroxymethyl-propyl cellulose and maltodextrin.
The film of embodiment 3~6 is evaluated, the results are shown in Table 2:
Table 2
The above result shows that hydroxymethyl-propyl cellulose: maltodextrin=3:2~1:2, with the increasing of maltodextrin
More, folding decreases, and disintegration time reduces, while film also becomes more to glue.
The film of embodiment 7~12 is evaluated, the results are shown in Table 3:
Table 3
The above result shows that the appearance of film is poor using glycerol as plasticizer, there is white particle precipitation.Either glycerol
Or 1,2-PD, as film plasticizer increases, folding has obvious improvement, has using glycerol as plasticizer preferable resistance to
Folding, but the disintegration time of film is longer；Poor as the folding of plasticizer film using 1,2-PD, disintegrating property is preferable.
The film of embodiment 13~15 is evaluated, the results are shown in Table 4:
Table 4
The above result shows that the appearance of film is preferable when 0.5:1~2:1 is mixed in proportion for 1,2-PD and glycerol,
There is preferable folding and disintegrating property simultaneously, when 1:1 is mixed in proportion for 1,2-PD and glycerol, effect is best.
The film of embodiment 16~18 is evaluated, the results are shown in Table 5:
Table 5
The above result shows that the viscosity of hydroxymethyl-propyl cellulose is 15cP, folding resistance and disintegrating property are preferable.
Wherein, the measuring mechanical property for the film that prepared by embodiment 5 as shown in Figure 1 (the result shows that elasticity modulus=
292.5±119.9(MPa)；6.6 ± 0.28 (MPamm of tensile strength-2)；Percent elongation 19.3% ± 0.3% (n=3),
Satisfactory mechanical property)；The content measuring chromatogram of film prepared by embodiment 5 is as shown in Figure 2.
Above-described specific embodiment has carried out further the purpose of the present invention, technical scheme and beneficial effects
It is described in detail, it should be understood that being not intended to limit the present invention the foregoing is merely a specific embodiment of the invention
Protection scope, all within the spirits and principles of the present invention, any modification, equivalent substitution, improvement and etc. done should all include
Within protection scope of the present invention.
Claims (10)
1. a kind of film rapidly-soluble in the oral cavity, which is characterized in that including following parts by weight of component:
0.09~0.155 parts by weight of active pharmaceutical ingredient, 0.6~1 parts by weight of water soluble film-forming material, plasticizer 0.15~0.3
Parts by weight, 0~0.1 parts by weight of disintegrating agent.
2. a kind of film rapidly-soluble in the oral cavity according to claim 1, which is characterized in that the water-soluble, film-forming
Material is including at least one in hydroxymethyl-propyl cellulose, maltodextrin, gelatin, hyaluronic acid, chitosan, cellulose acetate
Kind.
3. a kind of film rapidly-soluble in the oral cavity according to claim 2, which is characterized in that the water-soluble, film-forming
Material is the mixture of hydroxymethyl-propyl cellulose and maltodextrin.
4. a kind of film rapidly-soluble in the oral cavity according to claim 3, which is characterized in that the hydroxymethylpropyl
The weight ratio of cellulose and maltodextrin is 3:2~1:2.
5. a kind of film rapidly-soluble in the oral cavity according to claim 3, which is characterized in that the hydroxymethylpropyl
Cellulose is the hydroxypropyl methyl cellulose of viscosity 15cP.
6. a kind of film rapidly-soluble in the oral cavity according to claim 1, which is characterized in that the plasticizer is at least
Including one of 1,2- propylene glycol, glycerol.
7. a kind of film rapidly-soluble in the oral cavity according to claim 6, which is characterized in that when plasticizer is 1,2-
When the mixture of propylene glycol and glycerol, the weight ratio of 1,2-PD and glycerol is 0.5:1~2:1.
8. a kind of film rapidly-soluble in the oral cavity according to claim 1, which is characterized in that the pharmaceutical activity at
It is divided into Suo Malu peptide.
9. a kind of film rapidly-soluble in the oral cavity according to claim 1, which is characterized in that the disintegrating agent is pre-
Gelling starch.
10. a kind of, the preparation method of rapidly-soluble film, feature exist in the oral cavity as described in claim any one of 1-9
In, comprising the following steps:
1), water soluble film-forming material is dissolved in the water, obtains aqueous solution；
2) plasticizer and disintegrating agent are added in aqueous solution under stirring, are uniformly mixing to obtain dispersion liquid；
3), active pharmaceutical ingredient is added in dispersion liquid and is stirred evenly；
4), ultrasound removes bubble, and solution is spread evenly across on polymeric material culture dish；
5), blast heating is dry, and heat drying temperature is 40~60 DEG C, and the demoulding of stemness release agent is cut into required size and obtains mouth
The instant film of chamber.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910774122.9A CN110354106B (en) | 2019-08-21 | 2019-08-21 | Film agent capable of being rapidly dissolved in oral cavity and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910774122.9A CN110354106B (en) | 2019-08-21 | 2019-08-21 | Film agent capable of being rapidly dissolved in oral cavity and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110354106A true CN110354106A (en) | 2019-10-22 |
| CN110354106B CN110354106B (en) | 2023-03-24 |
Family
ID=68225000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910774122.9A Active CN110354106B (en) | 2019-08-21 | 2019-08-21 | Film agent capable of being rapidly dissolved in oral cavity and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110354106B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118490667A (en) * | 2024-05-31 | 2024-08-16 | 上海欣峰制药有限公司 | Orosity membrane, racecadotril orosity membrane agent, preparation method and preparation equipment thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009151072A1 (en) * | 2008-06-13 | 2009-12-17 | 大日本住友製薬株式会社 | Tablet quickly disintegrating in the oral cavity and method for producing the same |
| CN102824333A (en) * | 2012-09-26 | 2012-12-19 | 苏州大学 | Oral quick-dissolving film preparation and preparation method thereof |
| CN103211801A (en) * | 2013-04-02 | 2013-07-24 | 苏州人本药业有限公司 | Film agent quickly dissolved in oral cavity and preparation method thereof |
| CN104000800A (en) * | 2014-04-28 | 2014-08-27 | 万特制药(海南)有限公司 | Asenapine maleate oral instant membrane and making method thereof |
| CN105663096A (en) * | 2016-01-25 | 2016-06-15 | 南京济群医药科技有限公司 | Vonoprazan oral quick-dissolving film agent and method for preparing same |
| WO2018127938A1 (en) * | 2017-01-04 | 2018-07-12 | Jubeln Lifesciences Pvt. Ltd. | Oral dispersible film composition |
-
2019
- 2019-08-21 CN CN201910774122.9A patent/CN110354106B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009151072A1 (en) * | 2008-06-13 | 2009-12-17 | 大日本住友製薬株式会社 | Tablet quickly disintegrating in the oral cavity and method for producing the same |
| CN102824333A (en) * | 2012-09-26 | 2012-12-19 | 苏州大学 | Oral quick-dissolving film preparation and preparation method thereof |
| CN103211801A (en) * | 2013-04-02 | 2013-07-24 | 苏州人本药业有限公司 | Film agent quickly dissolved in oral cavity and preparation method thereof |
| CN104000800A (en) * | 2014-04-28 | 2014-08-27 | 万特制药(海南)有限公司 | Asenapine maleate oral instant membrane and making method thereof |
| CN105663096A (en) * | 2016-01-25 | 2016-06-15 | 南京济群医药科技有限公司 | Vonoprazan oral quick-dissolving film agent and method for preparing same |
| WO2018127938A1 (en) * | 2017-01-04 | 2018-07-12 | Jubeln Lifesciences Pvt. Ltd. | Oral dispersible film composition |
Non-Patent Citations (2)
| Title |
|---|
| ALIAA N. ELMESHAD，ARWA S. EL HAGRASY: "Characterization and Optimization of Orodispersible Mosapride Film Formulations", 《AAPS PHARMSCITECH》 * |
| 王倩等: "口腔速溶膜剂的研究进展", 《安徽医药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118490667A (en) * | 2024-05-31 | 2024-08-16 | 上海欣峰制药有限公司 | Orosity membrane, racecadotril orosity membrane agent, preparation method and preparation equipment thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110354106B (en) | 2023-03-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114796462B (en) | Long-acting GLP-1 derivative pharmaceutical preparation | |
| CN103800301B (en) | Pulsatile delivery composition for treating diabetes mellitus and preparation method thereof | |
| CA2887498A1 (en) | Compositions and methods for sustained delivery of glucagon-like peptide (glp-1) receptor agonist therapeutics | |
| US3928135A (en) | Process for the production of glucose polymers | |
| CN103002736B (en) | Methods of treating glucose metabolism disorders | |
| CN114632145B (en) | Insulin-loaded phenylboronic acid/fatty acid double-modified ε-polylysine particles and preparation method thereof | |
| Swain et al. | Bridging between disease, prevalence and treatment of diabetes mellitus: a review | |
| CN110354106A (en) | A kind of film rapidly-soluble in the oral cavity and preparation method thereof | |
| CN101909604A (en) | Methods for treating impaired glucose metabolism and glucose excursions | |
| CN104382874A (en) | Apixaban sustained-release tablets and preparation method thereof | |
| EP3871692B1 (en) | Pharmaceutical composition with blood sugar lowering effect | |
| CN112618526A (en) | Compound preparation for treating diabetes complicated with hypertension and preparation method thereof | |
| CN110974943A (en) | A kind of oral insulin pharmaceutical preparation and preparation method thereof | |
| WO2024041172A1 (en) | Microneedle for treating diabetes, and preparation process therefor | |
| CN105232490A (en) | Metformin hydrochloride sustained release tablet and preparation method thereof | |
| CN1751693A (en) | Application of astragalus polysaccharide in medicine for treating or preventing insulin resistance | |
| CN1785188A (en) | Compounding metformin glipidide prepn. for treating diabetes type II, and its prepn. method | |
| CN101342091A (en) | A method for establishing a model of impaired sugar regulation | |
| CN111437263A (en) | A kind of corncob total flavonoid solid dispersion osmotic pump tablet and preparation method thereof | |
| WO2014187302A1 (en) | Dulaglutide injection and preparation method thereof | |
| CN120733024A (en) | Sustained-release adjuvant and preparation method thereof | |
| CN118304389B (en) | A high-activity nattokinase composition and preparation method thereof | |
| CN117586347A (en) | A hirudin with antidiabetic activity and its application | |
| CN103623413A (en) | Preparation method and application of controlled release carrier material of sucrose ester | |
| Martynov et al. | Oral long-acting pharmaceutical form of insulin on the basis of self-organizing kvasi-living system of combinatorial peptides |
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 | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Gao Jian Inventor after: Li Yuanbo Inventor after: Dai Mei Inventor after: Chen Tingting Inventor after: Lu Yurong Inventor after: Liu Cailing Inventor before: Yu Shuang Inventor before: Gao Jian Inventor before: Li Yuanbo Inventor before: Dai Mei Inventor before: Yi Xiaojun Inventor before: Chen Tingting Inventor before: Lu Yurong Inventor before: Liu Cailing |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |