CN117257775A - Oral soluble film preparation for endometriosis and preparation method thereof - Google Patents
Oral soluble film preparation for endometriosis and preparation method thereof Download PDFInfo
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- CN117257775A CN117257775A CN202311445874.3A CN202311445874A CN117257775A CN 117257775 A CN117257775 A CN 117257775A CN 202311445874 A CN202311445874 A CN 202311445874A CN 117257775 A CN117257775 A CN 117257775A
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- Prior art keywords
- endometriosis
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- oral
- parts
- progesterone
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- 238000002360 preparation method Methods 0.000 title claims abstract description 99
- 201000009273 Endometriosis Diseases 0.000 title claims abstract description 67
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims abstract description 136
- 239000000186 progesterone Substances 0.000 claims abstract description 67
- 229960003387 progesterone Drugs 0.000 claims abstract description 67
- 239000003814 drug Substances 0.000 claims abstract description 59
- 239000000463 material Substances 0.000 claims abstract description 28
- 230000029087 digestion Effects 0.000 claims abstract description 21
- 239000012528 membrane Substances 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 17
- 239000004094 surface-active agent Substances 0.000 claims abstract description 13
- 229940100688 oral solution Drugs 0.000 claims abstract description 10
- 239000003292 glue Substances 0.000 claims description 27
- 239000000796 flavoring agent Substances 0.000 claims description 20
- 235000013355 food flavoring agent Nutrition 0.000 claims description 20
- 239000006184 cosolvent Substances 0.000 claims description 18
- 239000004014 plasticizer Substances 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 11
- 230000001590 oxidative effect Effects 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 238000005266 casting Methods 0.000 claims description 9
- 238000005520 cutting process Methods 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 239000003377 acid catalyst Substances 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 6
- 102000038379 digestive enzymes Human genes 0.000 claims description 6
- 108091007734 digestive enzymes Proteins 0.000 claims description 6
- -1 hydrocyanic acid compound Chemical class 0.000 claims description 6
- 239000000845 maltitol Substances 0.000 claims description 6
- 235000010449 maltitol Nutrition 0.000 claims description 6
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 6
- 229940035436 maltitol Drugs 0.000 claims description 6
- 239000012286 potassium permanganate Substances 0.000 claims description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 6
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 claims description 5
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 claims description 5
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 claims description 4
- 239000004382 Amylase Substances 0.000 claims description 3
- 102000013142 Amylases Human genes 0.000 claims description 3
- 108010065511 Amylases Proteins 0.000 claims description 3
- 108010011485 Aspartame Proteins 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
- 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 claims description 3
- 239000005715 Fructose Substances 0.000 claims description 3
- 229930091371 Fructose Natural products 0.000 claims description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 3
- 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 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 102000057297 Pepsin A Human genes 0.000 claims description 3
- 108090000284 Pepsin A Proteins 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 239000004721 Polyphenylene oxide Substances 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 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 claims description 3
- 102000004142 Trypsin Human genes 0.000 claims description 3
- 108090000631 Trypsin Proteins 0.000 claims description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 238000007259 addition reaction Methods 0.000 claims description 3
- 235000019418 amylase Nutrition 0.000 claims description 3
- 239000000605 aspartame Substances 0.000 claims description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 3
- 235000010357 aspartame Nutrition 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 3
- 239000003613 bile acid Substances 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 229960002737 fructose Drugs 0.000 claims description 3
- 210000004211 gastric acid Anatomy 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 229960001031 glucose Drugs 0.000 claims description 3
- 235000011187 glycerol Nutrition 0.000 claims description 3
- 229960005150 glycerol Drugs 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 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 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 3
- 229940111202 pepsin Drugs 0.000 claims description 3
- 239000000419 plant extract Substances 0.000 claims description 3
- 229920000570 polyether Polymers 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229950008882 polysorbate Drugs 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000006041 probiotic Substances 0.000 claims description 3
- 235000018291 probiotics Nutrition 0.000 claims description 3
- 239000008213 purified water Substances 0.000 claims description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019204 saccharin Nutrition 0.000 claims description 3
- 229940081974 saccharin Drugs 0.000 claims description 3
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 3
- 238000012216 screening Methods 0.000 claims description 3
- 239000000600 sorbitol Substances 0.000 claims description 3
- 229960002920 sorbitol Drugs 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 229960004793 sucrose Drugs 0.000 claims description 3
- 239000012588 trypsin Substances 0.000 claims description 3
- 229920002554 vinyl polymer Polymers 0.000 claims description 3
- 239000000811 xylitol Substances 0.000 claims description 3
- 235000010447 xylitol Nutrition 0.000 claims description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 3
- 229960002675 xylitol Drugs 0.000 claims description 3
- RBNPOMFGQQGHHO-UWTATZPHSA-N D-glyceric acid Chemical compound OC[C@@H](O)C(O)=O RBNPOMFGQQGHHO-UWTATZPHSA-N 0.000 claims description 2
- 239000012752 auxiliary agent Substances 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 239000000583 progesterone congener Substances 0.000 claims 2
- 230000002757 inflammatory effect Effects 0.000 abstract description 6
- 230000035755 proliferation Effects 0.000 abstract description 5
- 230000001105 regulatory effect Effects 0.000 abstract description 5
- 208000002193 Pain Diseases 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 208000024891 symptom Diseases 0.000 abstract description 4
- 230000002792 vascular Effects 0.000 abstract description 4
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 3
- 210000000987 immune system Anatomy 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 47
- 210000004379 membrane Anatomy 0.000 description 13
- 238000004090 dissolution Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 230000035935 pregnancy Effects 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000002357 endometrial effect Effects 0.000 description 5
- 210000002200 mouth mucosa Anatomy 0.000 description 5
- 230000027758 ovulation cycle Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 210000004291 uterus Anatomy 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010033372 Pain and discomfort Diseases 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 210000004696 endometrium Anatomy 0.000 description 2
- 238000010579 first pass effect Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003270 steroid hormone Substances 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- 208000004145 Endometritis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 206010036595 Premature delivery Diseases 0.000 description 1
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229960005471 androstenedione Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004246 corpus luteum Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000029849 luteinization Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000136 postovulatory effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an oral solution film preparation for endometriosis and a preparation method thereof, and relates to the technical field of oral solution film preparations, wherein the oral solution film preparation for endometriosis comprises the following raw materials in parts by weight: 40-50 parts of active medicine, 35-50 parts of high water-solubility film forming material, 1-5 parts of surfactant, 7-16 parts of premixed component and 3-6 parts of digestion aid, wherein the active medicine is progesterone, and the weight ratio of the progesterone is at least 1-50%. The oral-dissolving membrane preparation for endometriosis provided by the invention takes progesterone as an active medicine component, so that the oral-dissolving membrane preparation can play an anti-inflammatory role by inhibiting the release of inflammatory mediators and regulating the function of an immune system, relieve pain and inflammatory symptoms, inhibit the growth and proliferation of endometriosis focus, block the vascular supply of the endometriosis focus and reduce the volume and the quantity of the focus.
Description
Technical Field
The invention relates to the technical field of oral film preparations, in particular to an oral film preparation for endometriosis and a preparation method thereof.
Background
Endometriosis (endometritis) is a common gynaecological disease that occurs in places outside the uterus, usually in the pelvic cavity, and under normal conditions the endometrium is a layer of tissue located on the inner wall of the uterus that proliferates and falls off during the menstrual cycle of each month, whereas in Endometriosis, endometrial tissue occurs abnormally outside the uterus, such as the ovary, fallopian tube, pelvic wall, and peritoneum.
An orosol film preparation is a special preparation form, and refers to a film-like pharmaceutical preparation which can be rapidly dissolved and absorbed in the oral cavity, and the orosol film preparation is generally composed of a water-soluble polymer and other auxiliary components, and the components can enable the film to have good solubility and mouthfeel, so that the medicine can rapidly enter the blood circulation.
In the treatment of endometriosis, the oral mucosa preparation can rapidly release the drug and absorb the drug into the blood circulation, and the rapid drug release and absorption are helpful for relieving pain and discomfort caused by endometriosis, however, the physicochemical properties of the drug including solubility, stability, dissolution rate and the like need to be considered in the preparation of the oral mucosa preparation, and part of the drug may have lower solubility or slower dissolution rate, so that the prepared oral mucosa preparation cannot provide faster drug release and disintegration time limit, and further influence the absorption speed of patients.
For the problems in the related art, no effective solution has been proposed at present.
Disclosure of Invention
Aiming at the problems in the related art, the invention provides an oral soluble film preparation for endometriosis and a preparation method thereof, so as to overcome the technical problems in the prior art.
For this purpose, the invention adopts the following specific technical scheme:
according to one aspect of the present invention, there is provided an oral film preparation for endometriosis, which comprises the following raw materials in parts by weight:
40-50 parts of active medicine, 35-50 parts of high water-solubility film forming material, 1-5 parts of surfactant, 7-16 parts of ready-mixed component and 3-6 parts of digestion aid.
Further, the active drug is progesterone, and the weight ratio of the progesterone is at least 1-50%.
Further, the high water solubility film forming material comprises at least one of polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone and polyvinyl polyether.
Further, the ready-mixed components include plasticizers, flavoring agents and cosolvents.
Further, the plasticizer comprises at least one of sorbitol, polysorbate, xylitol, maltitol, glycerol, polyethylene glycol, propylene glycol, glycerate and fatty acid;
the flavoring agent comprises at least one of sucrose, glucose, fructose, saccharin, aspartame and maltitol;
the cosolvent comprises at least one of ethylene glycol, dimethyl sulfoxide, methanol, ethanol, acetone and dichloromethane.
Further, the digestion aid comprises at least one of digestive enzymes, probiotics, gastric acid inhibitors, bile acids, plant extracts and enzyme adjuvants;
the digestive enzyme comprises at least one of pepsin, trypsin and amylase.
According to another aspect of the present invention, there is also provided a method for preparing an oral film preparation for endometriosis, the method comprising the steps of:
s1, crushing and screening progesterone, and adding crushed progesterone into water for stirring and dissolving to obtain a stirring mixture;
s2, dispersing the high water-solubility film-forming material into purified water at 70-90 ℃, and stirring and dissolving to obtain a high water-solubility film-forming material solution;
s3, sequentially adding a high water-solubility film-forming material solution, a surfactant, ready-mixed components and a digestion aid into the stirring mixture, and homogenizing after uniformly stirring to obtain a medicine-containing layer glue solution;
s4, performing ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the defoamed medicine-containing layer glue solution into a film, and then performing drying treatment;
s5, cutting the dried film to obtain the oral soluble film preparation for endometriosis.
Further, the preparation method of the progesterone comprises the following steps:
carrying out addition reaction on acetone cyanohydrin and 4-androstenedione to obtain a hydrocyanic acid compound;
reacting a hydrocyanic acid compound with an acid catalyst and an organic solution, and separating the acid catalyst after the reaction to obtain a reaction solution;
oxidizing reaction liquid with a strong oxidizing catalyst to obtain a crude progesterone product;
and respectively crystallizing, washing and solvent extracting the crude progesterone to obtain high-purity refined progesterone.
Further, the acidic catalyst comprises at least one of boron trifluoride diethyl etherate, hydrochloric acid and sulfonic acid.
Further, the strong oxidizing catalyst is a mixture of sodium periodate and potassium permanganate, and the potassium permanganate accounts for 0.7-1% of the total mass of the strong oxidizing catalyst.
The beneficial effects of the invention are as follows:
1. the oral-dissolving membrane preparation for endometriosis provided by the invention takes progesterone as an active medicine component, so that the oral-dissolving membrane preparation can play an anti-inflammatory role by inhibiting the release of inflammatory mediators and regulating the function of an immune system, relieve pain and inflammatory symptoms, inhibit the growth and proliferation of endometriosis focus, block the vascular supply of the endometriosis focus and reduce the volume and the quantity of the focus.
2. The oral dissolving film preparation for endometriosis provided by the invention can take progesterone as an active medicine component, and selects proper carrier and preparation technology, and the progesterone is wrapped in a film with proper dissolution rate, so that the progesterone is rapidly dissolved and absorbed on oral mucosa, thereby providing faster medicine release and absorption rate, having shorter disintegration time and faster dissolution, improving bioavailability and curative effect of the medicine, being convenient for patients to use and carry, and simultaneously, the oral dissolving film preparation can also reduce first pass metabolism of the progesterone, and increase stability and tolerance of the medicine.
3. The oral membrane preparation for endometriosis provided by the invention can improve the solubility and absorbability of the medicine through the use of the plasticizer and the cosolvent, improve the bioavailability and curative effect of the medicine, and improve the taste and the taste of the oral membrane preparation through the use of the flavoring agent, thereby improving the satisfaction and compliance of patients.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a flowchart of a method for preparing an oral film preparation for endometriosis according to an embodiment of the present invention.
Detailed Description
For the purpose of further illustrating the various embodiments, the present invention provides the accompanying drawings, which are a part of the disclosure of the present invention, and which are mainly used for illustrating the embodiments and for explaining the principles of the operation of the embodiments in conjunction with the description thereof, and with reference to these matters, it will be apparent to those skilled in the art to which the present invention pertains that other possible embodiments and advantages of the present invention may be practiced.
According to an embodiment of the invention, an oral film preparation for endometriosis and a preparation method thereof are provided.
The invention will be further described with reference to the accompanying drawings and specific embodiments, wherein the oral film preparation for endometriosis according to the embodiment of the invention comprises the following raw materials in parts by weight:
40-50 parts of active medicine, 35-50 parts of high water-solubility film forming material, 1-5 parts of surfactant, 7-16 parts of ready-mixed component and 3-6 parts of digestion aid.
Wherein the active drug is progesterone, and the weight ratio of progesterone is at least 1-50%.
It should be noted that Progesterone (progestrone) is an endogenous steroid hormone and is also a synthetic artificial hormone which is secreted in females mainly by ovarian corpus luteum cells and is produced mainly by the placenta during pregnancy. The main functions of progesterone include:
regulating menstrual cycle: progesterone plays an important role in the second phase of the menstrual cycle, maintaining endometrial stability, promoting its shedding, and if no fertilization or pregnancy occurs, the progesterone level decreases, resulting in endometrial shedding, inducing menstrual onset.
Preparation of endometrium: progesterone promotes endometrial preparation during the post-ovulatory luteal phase, facilitates implantation of fertilized eggs and pregnancy, increases endometrial blood supply, and secretes fluid to provide nutrients for embryo development.
Maintenance of pregnancy: during pregnancy, the placenta secretes large amounts of progesterone, which plays an important role in maintaining pregnancy, and can inhibit uterine contraction, maintain relaxation of uterine smooth muscle, and prevent premature delivery.
The progesterone selected in the invention can inhibit the growth and proliferation of the endometriosis focus, reduce the volume and the number of the focus, block the vascular supply of the endometriosis focus by regulating the proliferation and apoptosis of cells in the endometriosis focus, and reduce the invasion and damage of the focus to surrounding tissues. Meanwhile, endometriosis is often accompanied by pain and inflammatory symptoms, and progesterone can reduce pain and discomfort caused by endometriosis by inhibiting inflammatory reaction and pain conduction.
Wherein the high water-solubility film forming material comprises at least one of polyvinyl alcohol, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone and polyvinyl polyether.
Wherein the ready-mixed component comprises a plasticizer, a flavoring agent and a cosolvent.
Wherein the plasticizer comprises at least one of sorbitol, polysorbate, xylitol, maltitol, glycerol, polyethylene glycol, propylene glycol, glyceride and fatty acid.
The flavoring agent comprises at least one of sucrose, glucose, fructose, saccharin, aspartame and maltitol.
The cosolvent comprises at least one of ethylene glycol, dimethyl sulfoxide, methanol, ethanol, acetone and dichloromethane.
Wherein the digestive aid comprises at least one of digestive enzyme, probiotics, gastric acid inhibitor, bile acid, plant extract and ferment auxiliary agent;
the digestive enzyme comprises at least one of pepsin, trypsin and amylase.
As shown in fig. 1, according to another embodiment of the present invention, there is also provided a method for preparing an oral film preparation for endometriosis, the method comprising the steps of:
s1, crushing and screening the progesterone, and adding the crushed progesterone into water for stirring and dissolving to obtain a stirring mixture.
Wherein, the preparation method of the progesterone comprises the following steps:
and (3) carrying out an addition reaction on acetone cyanohydrin and 4-androstenedione to obtain the hydrocyanic acid compound.
The weight ratio of acetone cyanohydrin to 4-androstenedione is 1.2-1.5: androstenedione is an important raw material and intermediate for synthesizing steroid hormone medicaments.
The hydrocyanic acid compound reacts with the acid catalyst and the organic solution, and the acid catalyst is separated after the reaction to obtain a reaction solution.
Wherein the acid catalyst comprises at least one of boron trifluoride diethyl etherate, hydrochloric acid and sulfonic acid.
And (3) carrying out an oxidation reaction on the reaction solution and a strong oxidizing catalyst to obtain a crude progesterone product.
Wherein the strong oxidizing catalyst is a mixture of sodium periodate and potassium permanganate, and the potassium permanganate accounts for 0.7-1% of the total mass of the strong oxidizing catalyst.
And respectively crystallizing, washing and solvent extracting the crude progesterone to obtain high-purity refined progesterone.
The method for preparing the high-purity progesterone fine product comprises the following steps of respectively crystallizing, washing and solvent extracting crude progesterone, wherein the steps are as follows:
the crude progesterone is dissolved in a suitable solvent, usually an organic solvent such as ethyl acetate or methanol, the solvent is heated to completely dissolve the progesterone, then the solution is slowly cooled to room temperature or low temperature, and the progesterone is gradually crystallized in the solution by stirring, ultrafiltration or centrifugation, etc.
The resulting crystals of progesterone are transferred to a washing device, which may be a filter funnel or a centrifuge, the crystals are dissolved with a washing liquid (usually a diluted solvent), and the solid is repeatedly washed with the washing liquid to remove impurities.
The washed progesterone solid is transferred into a solvent, usually an organic solvent such as ethyl acetate or acetone, and the progesterone is dissolved to form a solution, and the solution is reacted with an acidic or basic solution to adjust the solubility of the progesterone.
The recovered progesterone solution is subjected to acidification or alkalization treatment to adjust the pH value, the progesterone is recrystallized, and the refined progesterone is separated from the solvent by filtration, centrifugation or drying.
S2, dispersing the high water-solubility film-forming material into purified water at 70-90 ℃, and stirring and dissolving to obtain a high water-solubility film-forming material solution.
S3, sequentially adding the high-water-solubility film-forming material solution, the surfactant, the ready-mixed components and the digestion aid into the stirring mixture, and homogenizing after uniformly stirring to obtain the medicine-containing layer glue solution.
S4, performing ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the defoamed medicine-containing layer glue solution into a film, and then performing drying treatment.
S5, cutting the dried film to obtain the oral soluble film preparation for endometriosis.
The following is a further description of embodiments of the invention, taken in conjunction with the examples and comparative examples:
example 1
The oral membrane preparation for endometriosis comprises the following raw materials in parts by weight:
40 parts of progesterone, 35 parts of high water-solubility film forming material, 1 part of surfactant, 3 parts of plasticizer, 2 parts of flavoring agent, 2 parts of cosolvent and 3 parts of digestion aid.
The raw materials with the weight portions are selected, and the oral film preparation is prepared according to the preparation method of the oral film preparation for endometriosis, and the preparation method comprises the following steps:
sequentially adding a high water-solubility film forming material solution, a surfactant, a plasticizer, a flavoring agent, a cosolvent and a digestion aid into the progesterone mixture to obtain a medicine-containing layer glue solution, performing ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the medicine-containing layer glue solution subjected to the defoaming treatment into a film, drying the film, and cutting the dried film to obtain the oral solution film preparation for endometriosis.
Example 2
The oral membrane preparation for endometriosis comprises the following raw materials in parts by weight:
45 parts of progesterone, 40 parts of high water-solubility film forming material, 3 parts of surfactant, 4 parts of plasticizer, 3 parts of flavoring agent, 3 parts of cosolvent and 4 parts of digestion aid.
The raw materials with the weight portions are selected, and the oral film preparation is prepared according to the preparation method of the oral film preparation for endometriosis, and the preparation method comprises the following steps:
sequentially adding a high water-solubility film forming material solution, a surfactant, a plasticizer, a flavoring agent, a cosolvent and a digestion aid into the progesterone mixture to obtain a medicine-containing layer glue solution, performing ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the medicine-containing layer glue solution subjected to the defoaming treatment into a film, drying the film, and cutting the dried film to obtain the oral solution film preparation for endometriosis.
Example 3
The oral membrane preparation for endometriosis comprises the following raw materials in parts by weight:
50 parts of progesterone, 50 parts of high water-solubility film forming material, 5 parts of surfactant, 6 parts of plasticizer, 5 parts of flavoring agent, 5 parts of cosolvent and 6 parts of digestion aid.
The raw materials with the weight portions are selected, and the oral film preparation is prepared according to the preparation method of the oral film preparation for endometriosis, and the preparation method comprises the following steps:
sequentially adding a high water-solubility film forming material solution, a surfactant, a plasticizer, a flavoring agent, a cosolvent and a digestion aid into the progesterone mixture to obtain a medicine-containing layer glue solution, performing ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the medicine-containing layer glue solution subjected to the defoaming treatment into a film, drying the film, and cutting the dried film to obtain the oral solution film preparation for endometriosis.
Comparative example 1
The oral membrane preparation for endometriosis comprises the following raw materials in parts by weight:
40 parts of progesterone, 35 parts of high water-solubility film forming material, 3 parts of plasticizer, 2 parts of flavoring agent, 2 parts of cosolvent and 3 parts of digestion aid.
The raw materials with the weight portions are selected, and the oral film preparation is prepared according to the preparation method of the oral film preparation for endometriosis, and the preparation method comprises the following steps:
sequentially adding a high water-solubility film forming material solution, a plasticizer, a flavoring agent, a cosolvent and a digestion aid into the progesterone mixture to obtain a medicine-containing layer glue solution, carrying out ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the defoamed medicine-containing layer glue solution into a film, then carrying out drying treatment, and cutting the dried film to obtain the oral solution film preparation for endometriosis.
Comparative example 2
The oral membrane preparation for endometriosis comprises the following raw materials in parts by weight:
40 parts of progesterone, 35 parts of high water-solubility film forming material, 2 parts of flavoring agent, 2 parts of cosolvent and 3 parts of digestion aid.
The raw materials with the weight portions are selected, and the oral film preparation is prepared according to the preparation method of the oral film preparation for endometriosis, and the preparation method comprises the following steps:
sequentially adding a high water-solubility film forming material solution, a flavoring agent, a cosolvent and a digestion aid into the progesterone mixture to obtain a medicine-containing layer glue solution, performing ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the defoamed medicine-containing layer glue solution into a film, drying, and cutting the dried film to obtain the oral solution preparation for endometriosis.
Comparative example 3
An oral membrane preparation for endometriosis, which consists of the following raw materials in parts by weight.
40 parts of progesterone, 35 parts of high water-solubility film forming material, 2 parts of flavoring agent and 3 parts of digestion aid;
the raw materials with the weight portions are selected, and the oral film preparation is prepared according to the preparation method of the oral film preparation for endometriosis, and the preparation method comprises the following steps:
sequentially adding a high water-solubility film forming material solution, a flavoring agent and a digestion aid into the progesterone mixture to obtain a medicine-containing layer glue solution, carrying out ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the defoamed medicine-containing layer glue solution into a film, then carrying out drying treatment, and cutting the dried film to obtain the oral dissolving film preparation for endometriosis.
Table 1: comparative Table of oral film preparation Properties of examples and comparative examples
As shown in Table 1, the oral film preparation for endometriosis provided by the invention has better extensibility and tensile strength, and faster drug release and absorption speed, and also has shorter disintegration time and faster dissolution rate, so that the bioavailability and curative effect of the drug can be improved.
In summary, by means of the above technical solution, the oral membrane preparation for endometriosis provided by the invention uses progesterone as an active ingredient, so that the preparation can play an anti-inflammatory role by inhibiting the release of inflammatory mediators and regulating the function of an immune system, alleviate pain and inflammation symptoms, inhibit the growth and proliferation of endometriosis focus, block the vascular supply of endometriosis focus, and reduce the volume and the number of focus; the oral dissolving film preparation for endometriosis provided by the invention can take progesterone as an active medicine component, and selects proper carrier and preparation technology, and the progesterone is wrapped in a film with proper dissolution rate, so that the progesterone is rapidly dissolved and absorbed on oral mucosa, thereby providing faster medicine release and absorption rate, having shorter disintegration time limit and faster dissolution, improving bioavailability and curative effect of the medicine, being convenient for patients to use and carry, and simultaneously, the oral dissolving film preparation can also reduce first pass metabolism of the progesterone, and increase stability and tolerance of the medicine; the oral membrane preparation for endometriosis provided by the invention can improve the solubility and absorbability of the medicine through the use of the plasticizer and the cosolvent, improve the bioavailability and curative effect of the medicine, and improve the taste and the taste of the oral membrane preparation through the use of the flavoring agent, thereby improving the satisfaction and compliance of patients.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (10)
1. The oral membrane preparation for endometriosis is characterized by comprising the following raw materials in parts by weight:
40-50 parts of active medicine, 35-50 parts of high water-solubility film forming material, 1-5 parts of surfactant, 7-16 parts of ready-mixed component and 3-6 parts of digestion aid.
2. An endometriosis oral membrane preparation as claimed in claim 1, wherein the active drug is a progestin and the progestin is present in an amount of at least 1-50% by weight.
3. An endometriosis oral membrane preparation as claimed in claim 2, wherein the highly water-soluble membrane-forming material comprises at least one of polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone and polyvinyl polyether.
4. An endometriosis oral membrane preparation as claimed in claim 3, wherein the ready-mixed components comprise a plasticiser, a flavouring agent and a co-solvent.
5. An endometriosis oral membrane preparation as claimed in claim 4, wherein the plasticiser comprises at least one of sorbitol, polysorbate, xylitol, maltitol, glycerol, polyethylene glycol, propylene glycol, glycerate and fatty acid;
the flavoring agent comprises at least one of sucrose, glucose, fructose, saccharin, aspartame and maltitol;
the cosolvent comprises at least one of ethylene glycol, dimethyl sulfoxide, methanol, ethanol, acetone and dichloromethane.
6. An endometriosis oral membrane preparation as claimed in claim 5, wherein the digestion aid comprises at least one of digestive enzymes, probiotics, gastric acid inhibitors, bile acids, plant extracts and ferment auxiliary agents;
the digestive enzyme comprises at least one of pepsin, trypsin and amylase.
7. A method for producing an oral solution preparation for endometriosis, for achieving the production of an oral solution preparation for endometriosis as claimed in any one of claims 1 to 6, characterized in that the method comprises the steps of:
s1, crushing and screening progesterone, and adding crushed progesterone into water for stirring and dissolving to obtain a stirring mixture;
s2, dispersing the high-water-solubility film-forming material into purified water, and stirring and dissolving to obtain a high-water-solubility film-forming material solution;
s3, sequentially adding a high water-solubility film-forming material solution, a surfactant, ready-mixed components and a digestion aid into the stirring mixture, and homogenizing after uniformly stirring to obtain a medicine-containing layer glue solution;
s4, performing ultrasonic defoaming treatment on the medicine-containing layer glue solution, casting the defoamed medicine-containing layer glue solution into a film, and then performing drying treatment;
s5, cutting the dried film to obtain the oral soluble film preparation for endometriosis.
8. A method for preparing an oral film preparation for endometriosis as claimed in claim 7, wherein the method for preparing the progesterone comprises the following steps:
carrying out addition reaction on acetone cyanohydrin and 4-androstenedione to obtain a hydrocyanic acid compound;
reacting a hydrocyanic acid compound with an acid catalyst and an organic solution, and separating the acid catalyst after the reaction to obtain a reaction solution;
oxidizing reaction liquid with a strong oxidizing catalyst to obtain a crude progesterone product;
and respectively crystallizing, washing and solvent extracting the crude progesterone to obtain high-purity refined progesterone.
9. The method for producing an oral film preparation for endometriosis according to claim 8, wherein the acidic catalyst comprises at least one of boron trifluoride diethyl etherate, hydrochloric acid and sulfonic acid.
10. The method for preparing an oral film preparation for endometriosis according to claim 9, wherein the strong oxidizing catalyst is a mixture of sodium periodate and potassium permanganate, and the potassium permanganate accounts for 0.7-1% of the total mass of the strong oxidizing catalyst.
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