CN112972481A - Pharmaceutical composition, preparation method and application thereof - Google Patents
Pharmaceutical composition, preparation method and application thereof Download PDFInfo
- Publication number
- CN112972481A CN112972481A CN202110305079.9A CN202110305079A CN112972481A CN 112972481 A CN112972481 A CN 112972481A CN 202110305079 A CN202110305079 A CN 202110305079A CN 112972481 A CN112972481 A CN 112972481A
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- Prior art keywords
- pharmaceutical composition
- mixture
- wax
- polyethylene glycol
- raw materials
- Prior art date
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Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 86
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 229960004434 doxycycline monohydrate Drugs 0.000 claims abstract description 29
- 239000002994 raw material Substances 0.000 claims abstract description 24
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 19
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 15
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 15
- -1 liquid paraffin Substances 0.000 claims abstract description 13
- 239000011159 matrix material Substances 0.000 claims abstract description 11
- 125000005456 glyceride group Chemical group 0.000 claims abstract description 9
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229920002472 Starch Polymers 0.000 claims abstract description 8
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000019698 starch Nutrition 0.000 claims abstract description 8
- 239000008107 starch Substances 0.000 claims abstract description 8
- 239000001993 wax Substances 0.000 claims abstract description 8
- 239000000758 substrate Substances 0.000 claims abstract description 7
- 235000019483 Peanut oil Nutrition 0.000 claims abstract description 6
- 239000004200 microcrystalline wax Substances 0.000 claims abstract description 6
- 235000019808 microcrystalline wax Nutrition 0.000 claims abstract description 6
- 239000000312 peanut oil Substances 0.000 claims abstract description 6
- WECGLUPZRHILCT-GSNKCQISSA-N 1-linoleoyl-sn-glycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)CO WECGLUPZRHILCT-GSNKCQISSA-N 0.000 claims abstract description 5
- OVYMWJFNQQOJBU-UHFFFAOYSA-N 1-octanoyloxypropan-2-yl octanoate Chemical compound CCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC OVYMWJFNQQOJBU-UHFFFAOYSA-N 0.000 claims abstract description 5
- NFIHXTUNNGIYRF-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate Chemical compound CCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCCC NFIHXTUNNGIYRF-UHFFFAOYSA-N 0.000 claims abstract description 5
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 claims abstract description 5
- 150000002334 glycols Chemical class 0.000 claims abstract description 5
- 239000004209 oxidized polyethylene wax Substances 0.000 claims abstract description 5
- 235000013873 oxidized polyethylene wax Nutrition 0.000 claims abstract description 5
- 239000004698 Polyethylene Substances 0.000 claims abstract description 4
- 239000004743 Polypropylene Substances 0.000 claims abstract description 4
- 229920000573 polyethylene Polymers 0.000 claims abstract description 4
- 229920001155 polypropylene Polymers 0.000 claims abstract description 4
- 239000008159 sesame oil Substances 0.000 claims abstract description 4
- 235000011803 sesame oil Nutrition 0.000 claims abstract description 4
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 claims abstract 5
- 239000000203 mixture Substances 0.000 claims description 48
- 239000003814 drug Substances 0.000 claims description 16
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
- 239000008119 colloidal silica Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 108010011485 Aspartame Proteins 0.000 claims description 12
- 235000010357 aspartame Nutrition 0.000 claims description 12
- 239000000605 aspartame Substances 0.000 claims description 12
- 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 12
- 229960003438 aspartame Drugs 0.000 claims description 12
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 12
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 12
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 8
- 241000287828 Gallus gallus Species 0.000 claims description 8
- 235000015278 beef Nutrition 0.000 claims description 8
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 8
- 210000004185 liver Anatomy 0.000 claims description 8
- 229910021645 metal ion Inorganic materials 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 239000008139 complexing agent Substances 0.000 claims description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 230000000844 anti-bacterial effect Effects 0.000 claims description 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 235000006708 antioxidants Nutrition 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- 239000002562 thickening agent Substances 0.000 claims description 6
- BVCOHOSEBKQIQD-UHFFFAOYSA-N 2-tert-butyl-6-methoxyphenol Chemical compound COC1=CC=CC(C(C)(C)C)=C1O BVCOHOSEBKQIQD-UHFFFAOYSA-N 0.000 claims description 5
- 230000003078 antioxidant effect Effects 0.000 claims description 5
- 229940110456 cocoa butter Drugs 0.000 claims description 5
- 235000019868 cocoa butter Nutrition 0.000 claims description 5
- 235000013355 food flavoring agent Nutrition 0.000 claims description 5
- 239000004034 viscosity adjusting agent Substances 0.000 claims description 5
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 claims description 4
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 4
- 239000001814 pectin Substances 0.000 claims description 4
- 235000010987 pectin Nutrition 0.000 claims description 4
- 229920001277 pectin Polymers 0.000 claims description 4
- 229940013618 stevioside Drugs 0.000 claims description 4
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 4
- 235000019202 steviosides Nutrition 0.000 claims description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 3
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 3
- 244000215068 Acacia senegal Species 0.000 claims description 3
- 229920001353 Dextrin Polymers 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 3
- 229920000084 Gum arabic Polymers 0.000 claims description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 3
- 239000004376 Sucralose Substances 0.000 claims description 3
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 3
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 3
- 235000010489 acacia gum Nutrition 0.000 claims description 3
- 239000000205 acacia gum Substances 0.000 claims description 3
- 229940072056 alginate Drugs 0.000 claims description 3
- 235000010443 alginic acid Nutrition 0.000 claims description 3
- 229920000615 alginic acid Polymers 0.000 claims description 3
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 239000000499 gel Substances 0.000 claims description 3
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 3
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 3
- 229960005055 sodium ascorbate Drugs 0.000 claims description 3
- 229940001607 sodium bisulfite Drugs 0.000 claims description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 3
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 3
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 3
- 235000019408 sucralose Nutrition 0.000 claims description 3
- 229940080258 tetrasodium iminodisuccinate Drugs 0.000 claims description 3
- GYBINGQBXROMRS-UHFFFAOYSA-J tetrasodium;2-(1,2-dicarboxylatoethylamino)butanedioate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CC(C([O-])=O)NC(C([O-])=O)CC([O-])=O GYBINGQBXROMRS-UHFFFAOYSA-J 0.000 claims description 3
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical class COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 235000015067 sauces Nutrition 0.000 claims description 2
- 238000011861 anti-inflammatory therapy Methods 0.000 claims 1
- 241000282326 Felis catus Species 0.000 abstract description 12
- 241000282472 Canis lupus familiaris Species 0.000 abstract description 11
- 229960003722 doxycycline Drugs 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 9
- 241000894006 Bacteria Species 0.000 abstract description 7
- 206010061218 Inflammation Diseases 0.000 abstract description 7
- 230000004054 inflammatory process Effects 0.000 abstract description 7
- 235000019629 palatability Nutrition 0.000 abstract description 7
- 238000003860 storage Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract 1
- FZKWRPSUNUOXKJ-CVHRZJFOSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrate Chemical compound O.C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O FZKWRPSUNUOXKJ-CVHRZJFOSA-N 0.000 description 35
- 229940079593 drug Drugs 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 210000003238 esophagus Anatomy 0.000 description 5
- 210000002784 stomach Anatomy 0.000 description 5
- PTNZGHXUZDHMIQ-UHFFFAOYSA-N 4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C)C(C(O)C3C(C(O)=C(C(N)=O)C(=O)C3N(C)C)(O)C3=O)C3=C(O)C2=C1O PTNZGHXUZDHMIQ-UHFFFAOYSA-N 0.000 description 3
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 3
- 239000004098 Tetracycline Substances 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 210000000795 conjunctiva Anatomy 0.000 description 3
- 229960004082 doxycycline hydrochloride Drugs 0.000 description 3
- 229940041667 oral paste Drugs 0.000 description 3
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 3
- 229960002180 tetracycline Drugs 0.000 description 3
- 229930101283 tetracycline Natural products 0.000 description 3
- 235000019364 tetracycline Nutrition 0.000 description 3
- 150000003522 tetracyclines Chemical class 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 241000606161 Chlamydia Species 0.000 description 2
- 208000007190 Chlamydia Infections Diseases 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 2
- 208000036071 Rhinorrhea Diseases 0.000 description 2
- 206010039101 Rhinorrhoea Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 229940057847 polyethylene glycol 600 Drugs 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 206010041232 sneezing Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 239000001201 calcium disodium ethylene diamine tetra-acetate Substances 0.000 description 1
- 235000011188 calcium disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- PHALYIWLKRSLME-UHFFFAOYSA-N decanoic acid;2,3-dihydroxypropyl octanoate Chemical group CCCCCCCCCC(O)=O.CCCCCCCC(=O)OCC(O)CO PHALYIWLKRSLME-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
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- 238000001727 in vivo Methods 0.000 description 1
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- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
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- 231100000344 non-irritating Toxicity 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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- 239000004250 tert-Butylhydroquinone Substances 0.000 description 1
- 235000019281 tert-butylhydroquinone Nutrition 0.000 description 1
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- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
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Classifications
-
- 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
- A61K31/65—Tetracyclines
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention relates to a pharmaceutical composition, a preparation method and application thereof. The pharmaceutical composition is prepared from the following raw materials in percentage by mass: 5 to 30 percent of doxycycline monohydrate; 1% -20% of a substrate carrier; 50% -80% of viscosity regulator; the matrix carrier is at least one of caprylic/capric polyethylene glycol glyceride, propylene glycol dicaprylate/dicaprate, starch, liquid paraffin, peanut oil and sesame oil; the viscosity regulator is selected from at least one of microcrystalline wax, polyethylene wax, oxidized polyethylene wax, polypropylene wax, polyethylene glycol compounds, medium-chain triglyceride and glycerol monolinoleate. The pharmaceutical composition can remarkably improve the bioavailability of doxycycline on cats and dogs, has quick effect after being orally taken by dogs and cats, and can quickly resist bacteria and diminish inflammation. In addition, the pharmaceutical composition has good stability, easy storage, good palatability, easy popularization and industrial production, and wide application prospect.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a pharmaceutical composition and a preparation method and application thereof.
Background
Doxycycline (Doxycycline), an alloname in chinese is Doxycycline; CAS number 564-25-0 molecular formula C22H24N2O8, molecular weight 444.4346. It is a broad-spectrum antibiotic of tetracycline, has 10 times stronger antibiotic action than tetracycline, still has effect on tetracycline-resistant bacteria, and has inhibitory action on gram-negative bacteria, gram-positive bacteria, spirochete, rickettsia, mycoplasma, chlamydia, etc. It is mainly used for treating various diseases of pets in veterinary clinic.
At present, the antibacterial and anti-inflammatory medicines for pets clinically are mainly foreign brands, such as American Shuoyeng, French Weilong and the like, domestic independently-developed pet medicines are few, most of the medicines are cattle, sheep or human medicines for pets, the risk and the uncertainty of clinical use are increased, and meanwhile, the curative effect cannot be ensured. Most of the medicines are mainly injections and tablets, so that the use is inconvenient, and the problem that the pet such as cats, dogs and the like is difficult to feed the tablets is also solved. In contrast, oral paste is a particularly convenient form of preparation for animals such as cats and dogs, and is convenient to administer and easy to store, but oral paste is mainly used for treatment of horses and pets abroad, and is rarely used in domestic markets.
Disclosure of Invention
In order to solve the problems, the invention provides a pharmaceutical composition which contains doxycycline drugs, has good stability, is semisolid, is convenient to administer and has small toxic and side effects, and can be used for pet and human to resist bacteria and diminish inflammation.
The technical scheme is as follows:
a pharmaceutical composition is prepared from the following raw materials in percentage by mass:
5 to 30 percent of doxycycline monohydrate;
1% -20% of a substrate carrier;
50% -80% of viscosity regulator;
the matrix carrier is at least one of caprylic/capric polyethylene glycol glyceride, propylene glycol dicaprylate/dicaprate, starch, liquid paraffin, peanut oil and sesame oil;
the viscosity regulator is selected from at least one of microcrystalline wax, polyethylene wax, oxidized polyethylene wax, polypropylene wax, polyethylene glycol compounds, medium-chain triglyceride and glycerol monolinoleate.
In one embodiment, the pharmaceutical composition is prepared from the following raw materials in percentage by mass:
doxycycline monohydrate 10% -25%;
2% -15% of a substrate carrier;
60 to 75 percent of viscosity regulator.
In one embodiment, the medium chain triglyceride is glyceryl caprylate capric acid and the liquid paraffin is light liquid paraffin.
In one embodiment, the weight average molecular weight of the polyethylene glycol compound is 200-1200.
In one embodiment, the polyethylene glycol is selected from at least one of polyethylene glycol-200, polyethylene glycol-400, and polyethylene glycol-600.
In one embodiment, the pharmaceutical composition is prepared from the following raw materials in percentage by mass:
in one embodiment, the flavoring agent is selected from at least one of chicken liver powder, beef sauce, cocoa butter, and vanillin compounds.
In one embodiment, the antioxidant is selected from at least one of t-butyl hydroxyanisole, t-butyl hydroquinone, sodium metabisulfite, sodium ascorbate, and sodium bisulfite.
In one embodiment, the sweetener is selected from at least one of aspartame, stevia, and sucralose and trehalose.
In one embodiment, the metal ion complexing agent is selected from at least one of tetrasodium iminodisuccinate, disodium ethylenediaminetetraacetate, calcium disodium ethylenediaminetetraacetate, citric acid, and glycine.
In one embodiment, the thickening agent is selected from at least one of starch, gum arabic, pectin, alginate gel, dextrin, and colloidal silica.
The invention also provides a preparation method of the pharmaceutical composition, which comprises the following steps:
mixing the matrix carrier and the viscosity modifier to prepare a first mixture;
mixing the doxycycline monohydrate and the first mixture.
The invention also provides application of the pharmaceutical composition in preparation of antibacterial and anti-inflammatory medicines.
Compared with the prior art, the invention has the following beneficial effects:
the raw materials for preparing the pharmaceutical composition comprise doxycycline monohydrate, a specific matrix carrier and a viscosity regulator. Wherein, doxycycline monohydrate is used as the main antibacterial and anti-inflammatory active ingredient, and belongs to an alkaline compound, which can not reduce the pH value of esophagus and stomach of a user. The pharmaceutical composition is in a semisolid state, a paste form and easy administration through the action of a matrix and a viscosity regulator. Compared with the common chewable tablets, the pharmaceutical composition provided by the invention can significantly improve the bioavailability of doxycycline on cats and dogs, and the pharmaceutical composition provided by the invention has quick effect after being taken by dogs and cats, and can quickly resist bacteria and diminish inflammation. In addition, the pharmaceutical composition provided by the invention has good stability and palatability, is easy to popularize and industrially produce, and has wide application prospects.
Detailed Description
The present invention will be described in further detail with reference to specific examples. The present invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
In the present invention, medium chain triglycerides represent glycerides (MCT) corresponding to fatty acids having a carbon chain of 6 to 12 carbon atoms.
The oral paste can be used as a particularly convenient preparation form applied to animals such as cats, dogs and the like, is convenient to administer and easy to store, but is mainly used for treating horses and pets abroad and is rare in domestic markets.
Doxycycline monohydrate and doxycycline hydrochloride are two different existing forms of doxycycline, the two have similar drug effects, the bioavailability is not different, and the main differences are shown in table 1.
TABLE 1 doxycycline hydrochloride and doxycycline monohydrate control
Doxycycline hydrochloride is reported to readily dissociate hydrochloric acid, reducing the formation of low pH in the esophagus and stomach of animals, and to risk causing ulcers in the esophagus and stomach of pets. The doxycycline monohydrate is an alkaline compound, and does not lower the pH value of esophagus and stomach.
Therefore, the invention selects the Qiangliumcao monohydrate as the main active medicament, can efficiently resist bacteria and diminish inflammation, and can effectively avoid the side effect of the medicament.
The technical scheme is as follows:
a pharmaceutical composition is prepared from the following raw materials in percentage by mass:
5 to 30 percent of doxycycline monohydrate;
1% -20% of a substrate carrier;
50% -80% of viscosity regulator;
the matrix carrier is at least one of caprylic/capric polyethylene glycol glyceride, propylene glycol dicaprylate/dicaprate, starch, liquid paraffin, peanut oil and sesame oil;
the viscosity regulator is selected from at least one of microcrystalline wax, polyethylene wax, oxidized polyethylene wax, polypropylene wax, polyethylene glycol compounds, medium-chain triglyceride and glycerol monolinoleate.
The raw materials for preparing the pharmaceutical composition comprise doxycycline monohydrate, a specific matrix carrier and a viscosity regulator. Wherein, doxycycline monohydrate is used as the main antibacterial and anti-inflammatory active ingredient, and belongs to an alkaline compound, which can not reduce the pH value of esophagus and stomach of a user. The pharmaceutical composition is in a semisolid state, a paste form and easy administration through the action of a matrix and a viscosity regulator. Compared with the common chewable tablets, the pharmaceutical composition provided by the invention can significantly improve the bioavailability of doxycycline on cats and dogs, and the pharmaceutical composition provided by the invention has quick effect after being taken by dogs and cats, and can quickly resist bacteria and diminish inflammation. In addition, the pharmaceutical composition provided by the invention has good stability and palatability, is easy to popularize and industrially produce, and has wide application prospects.
In one preferred embodiment, the pharmaceutical composition is prepared from the following raw materials in percentage by mass:
doxycycline monohydrate 10% -25%;
2% -15% of a substrate carrier;
60 to 75 percent of viscosity regulator.
Controlling the ratio of the raw materials within this range is more advantageous in that the pharmaceutical composition is in a semi-solid form, paste form, easy to administer, and better in drug efficacy, stability, and palatability, by the action of the base and the viscosity modifier.
Preferably, the base carrier is liquid paraffin. In one of the preferred embodiments, the liquid paraffin is light liquid paraffin, which has a lower density and better flowability.
Preferably, the viscosity modifier is a medium chain triglyceride. In one preferred embodiment, the medium chain triglyceride is caprylic capric acid glyceride, and the viscosity of the medium chain triglyceride is lower, so that a microemulsion can be formed in vivo, and the bioavailability of the medicament is increased.
In one embodiment, the raw materials used to prepare the pharmaceutical composition of the present invention further comprise flavoring agents, antioxidants, sweeteners, metal ion complexing agents, and thickening agents.
Wherein, the flavoring agent can increase the palatability of the medicine and is beneficial to administration. Preferably, the flavor is selected from at least one of chicken liver powder, beef paste, cocoa butter and vanillin compounds.
The use of the metal ion complexing agent can solve the problem of chelation between metal ions and doxycycline under different water quality conditions, thereby enhancing the stability of the preparation. Preferably, the metal ion complexing agent is selected from at least one of tetrasodium iminodisuccinate, disodium ethylenediaminetetraacetate, disodium calcium ethylenediaminetetraacetate, citric acid, and glycine. More preferably, the metal ion complexing agent is selected from disodium ethylenediaminetetraacetate and/or disodium calcium ethylenediaminetetraacetate. Most preferably, the metal ion complexing agent is selected from disodium ethylenediaminetetraacetate.
The antioxidant can avoid the oxidation problem of doxycycline in the production, storage and transportation processes, and ensure the stability of the pharmaceutical composition. Preferably, the antioxidant is selected from at least one of tert-butyl hydroxyanisole, tert-butyl hydroquinone, sodium metabisulfite, sodium ascorbate and sodium bisulfite. Preferably, the antioxidant is selected from sodium pyrosulfite.
The sweetener can reduce the bitter taste of doxycycline monohydrate. Preferably, the sweetener is selected from at least one of aspartame, stevioside, sucralose and trehalose. More preferably, the sweetener is aspartame.
The thickening agent can improve the system consistency, so that the medicine composition of the invention keeps a uniform and stable suspended state or an opacified state. Preferably, the thickener is selected from at least one of starch, gum arabic, pectin, alginate gel, dextrin and colloidal silica. Preferably, the thickening agent is selected from colloidal silica, and a small amount of colloidal silica achieves a good thickening effect.
In one preferred embodiment, the pharmaceutical composition is prepared from the following raw materials in percentage by mass:
in one embodiment, the weight average molecular weight of the polyethylene glycol compound is 200-1200. Such polyethylene glycol compounds have better fluidity.
In one embodiment, the polyethylene glycol is selected from at least one of polyethylene glycol-200, polyethylene glycol-400, and polyethylene glycol-600.
The invention also provides a preparation method of the pharmaceutical composition, which comprises the following steps:
mixing the matrix carrier and the viscosity modifier to prepare a first mixture;
mixing the doxycycline monohydrate and the first mixture.
By the preparation method, the components can be uniformly mixed, so that the doxycycline monohydrate is prevented from being difficult to disperse in a solid-liquid mixture, and the preparation method is favorable for preparing the pharmaceutical composition with stable performance and uniform quality.
The invention also provides application of the pharmaceutical composition in preparation of antibacterial and anti-inflammatory medicines.
The following are specific examples.
Unless otherwise specified, all starting materials are derived from commercially available products, and if not specified, contain no other components not specifically specified except for unavoidable impurities.
Example 1
The present example provides a pharmaceutical composition and a method for preparing the same.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
uniformly mixing caprylic capric acid glyceride and light liquid paraffin at 45 ℃ to prepare a mixture A;
uniformly mixing doxycycline monohydrate, chicken liver powder, disodium ethylenediamine tetraacetic acid, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 2
The present example provides a pharmaceutical composition and a method for preparing the same.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
uniformly mixing caprylic capric acid glyceride and light liquid paraffin at 45 ℃ to prepare a mixture A;
uniformly mixing doxycycline monohydrate, beef paste, disodium edetate, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 3
The present example provides a pharmaceutical composition and a method for preparing the same.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
dissolving cocoa butter at 45 ℃, adding caprylic capric glyceride and light liquid paraffin, and uniformly mixing to prepare a mixture A;
uniformly mixing doxycycline monohydrate, disodium ethylene diamine tetraacetate, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 4
The present example provides a pharmaceutical composition and a method for preparing the same.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
dissolving cocoa butter at 45 ℃, adding caprylic capric glyceride and light liquid paraffin, and uniformly mixing to prepare a mixture A;
uniformly mixing doxycycline monohydrate, disodium ethylene diamine tetraacetate, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 5
The present example provides a pharmaceutical composition and a method for preparing the same.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
adding polyethylene glycol-200 and light liquid paraffin at 45 ℃, and uniformly mixing to prepare a mixture A;
uniformly mixing doxycycline monohydrate, disodium ethylene diamine tetraacetate, a vanillin compound, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 6
The present example provides a pharmaceutical composition and a method for preparing the same. The main difference compared to example 1 is the replacement of the light liquid paraffin by peanut oil.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
uniformly mixing caprylic capric acid glyceride and peanut oil at 45 ℃ to prepare a mixture A;
uniformly mixing doxycycline monohydrate, chicken liver powder, disodium ethylenediamine tetraacetic acid, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 7
The present example provides a pharmaceutical composition and a method for preparing the same. The main difference compared to example 1 is the replacement of the light liquid paraffin by caprylic/capric macrogol glycerides.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
uniformly mixing caprylic capric acid glyceride and caprylic/capric acid polyethylene glycol glyceride at 45 ℃ to prepare a mixture A;
uniformly mixing doxycycline monohydrate, chicken liver powder, disodium ethylenediamine tetraacetic acid, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 8
The present example provides a pharmaceutical composition and a method for preparing the same. Compared with example 1, the main difference is that microcrystalline wax is used for replacing caprylic capric acid glyceride, and beef paste is used for replacing chicken liver powder.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
uniformly mixing microcrystalline wax and light liquid paraffin at 45 ℃ to prepare a mixture A;
uniformly mixing doxycycline monohydrate, beef paste, disodium edetate, aspartame, sodium metabisulfite and the mixture A at 45 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 45 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 9
The present example provides a pharmaceutical composition and a method for preparing the same.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
uniformly mixing starch and glycerol monolinoleate at 50 ℃ to prepare a mixture A;
uniformly mixing doxycycline monohydrate, chicken liver powder, disodium ethylenediamine tetraacetic acid, stevioside, tert-butyl hydroxyanisole and the mixture A at 50 ℃ to prepare a mixture B;
the colloidal silica and the mixture B were mixed uniformly at 50 ℃ to give 250g of the pharmaceutical composition, and finally the paste was filled into a dispenser and packed in a size of 2.5 g/piece.
Example 10
The present example provides a pharmaceutical composition and a method for preparing the same.
(1) The pharmaceutical composition provided by the embodiment is prepared from the following raw materials in percentage by mass:
(2) the preparation method of the pharmaceutical composition provided in this embodiment includes the following steps:
uniformly mixing oxidized polyethylene wax and propylene glycol dicaprylate/dicaprate at 50 ℃ to prepare a mixture A;
uniformly mixing doxycycline monohydrate, beef paste, disodium ethylenediamine tetraacetic acid, stevioside, tert-butyl hydroxyanisole and the mixture A at 50 ℃ to prepare a mixture B;
mixing pectin and mixture B at 50 deg.C to obtain 250g of pharmaceutical composition, and packaging the paste in a container with a size of 2.5 g/piece.
Test examples
(1) Product properties and stability:
the products of examples 1 to 10 are non-toxic, non-irritating, brown semi-solid and can be stored for two years at 15 ℃ to 30 ℃.
(2) Animal palatability experiments:
the palatability tests of the products of examples 1 to 5 were carried out using the double pot method on 30 cats and 30 dogs, 6 per example, using the animal approach number and first bite preference as indices, and the results are shown in table 2.
TABLE 2
As can be seen from table 2, the use of beef paste as a flavoring agent has a better appeal for dogs and cats.
(3) The application comprises the following steps:
20 cases of upper respiratory tract infection and chlamydia infection of cats were collected in two pet hospitals in Guangzhou city, and mainly manifested by sneezing, rhinorrhea, edema and ulcer of conjunctiva and conjunctiva, secretion increase and bronchial inflammation, laboratory tests showed chlamydia infection, calicivirus, herpes virus and other infections, and blood routinely showed an increase in white blood cell count.
The treatment scheme comprises the following steps: the groups were randomized, and 5 cases were divided into 4 groups. The first group of cases was treated with the pharmaceutical composition prepared in example 1 of the present invention (doxycycline paste) twice daily at 0.25g each for two weeks. The second group of cases was treated twice daily, 0.25g each, for two weeks with the pharmaceutical composition prepared in example 2 of the present invention. The third group of cases was treated twice daily with 0.25g of the pharmaceutical composition prepared in example 7 of the present invention for two weeks. The fourth group of cases was treated with the pharmaceutical composition prepared in example 8 of the present invention twice daily at 0.25g each time for two weeks.
The effect is as follows: after two weeks, the patients were examined for sneezing, rhinorrhea, edema and ulcer of conjunctiva, secretion increase, bronchial inflammation and other symptoms, and normal counts of chlamydia, calicivirus, herpes virus and blood conventional leukocytes were examined. The results are shown in Table 3.
TABLE 3
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. The pharmaceutical composition is characterized by being prepared from the following raw materials in percentage by mass:
5 to 30 percent of doxycycline monohydrate;
1% -20% of a substrate carrier;
50% -80% of viscosity regulator;
the matrix carrier is at least one of caprylic/capric polyethylene glycol glyceride, propylene glycol dicaprylate/dicaprate, starch, liquid paraffin, peanut oil and sesame oil;
the viscosity regulator is selected from at least one of microcrystalline wax, polyethylene wax, oxidized polyethylene wax, polypropylene wax, polyethylene glycol compounds, medium-chain triglyceride and glycerol monolinoleate.
2. The pharmaceutical composition according to claim 1, which is prepared from the following raw materials in percentage by mass:
doxycycline monohydrate 10% -25%;
2% -15% of a substrate carrier;
60 to 75 percent of viscosity regulator.
3. The pharmaceutical composition of claim 1 or 2, wherein the medium chain triglyceride is caprylic capric glyceride and the liquid paraffin is light liquid paraffin; and/or
The weight average molecular weight of the polyethylene glycol compound is 200-1200.
4. The pharmaceutical composition according to claim 1, which is prepared from the following raw materials in percentage by mass:
5. the pharmaceutical composition of claim 4, wherein the flavoring agent is selected from at least one of chicken liver powder, beef sauce, cocoa butter, and vanillin compounds.
6. The pharmaceutical composition of claim 4, wherein the antioxidant is selected from at least one of t-butyl hydroxyanisole, t-butyl hydroquinone, sodium metabisulfite, sodium ascorbate, and sodium bisulfite; and/or
The sweetener is selected from at least one of aspartame, stevioside, sucralose and trehalose.
7. The pharmaceutical composition of claim 4, wherein the metal ion complexing agent is selected from at least one of tetrasodium iminodisuccinate, disodium ethylenediaminetetraacetate, disodium calcium ethylenediaminetetraacetate, citric acid, and glycine.
8. The pharmaceutical composition of claim 4, wherein the thickening agent is selected from at least one of starch, gum arabic, pectin, alginate gel, dextrin, and colloidal silica.
9. A process for the preparation of a pharmaceutical composition according to any one of claims 1 to 8, comprising the steps of:
mixing the matrix carrier and the viscosity modifier to prepare a first mixture;
mixing the doxycycline monohydrate and the first mixture.
10. Use of a pharmaceutical composition according to any one of claims 1 to 8 for the manufacture of a medicament for antibacterial and anti-inflammatory therapy.
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2021
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| CN1262130A (en) * | 1999-01-29 | 2000-08-09 | 许亮 | Application of complexon in veterinary medicines |
| CN1341022A (en) * | 1999-02-23 | 2002-03-20 | 麦克公司 | Pharmaceutical composition containing porton pump inhibitors |
| CN106176611A (en) * | 2016-08-12 | 2016-12-07 | 上海邦森生物科技有限公司 | A kind of doxycycline compound formulation of stability and high efficiency and preparation method thereof |
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Application publication date: 20210618 |