WO2016126217A1 - Stable pharmaceutical combination containing benzydamine - Google Patents
Stable pharmaceutical combination containing benzydamine Download PDFInfo
- Publication number
- WO2016126217A1 WO2016126217A1 PCT/TR2015/000038 TR2015000038W WO2016126217A1 WO 2016126217 A1 WO2016126217 A1 WO 2016126217A1 TR 2015000038 W TR2015000038 W TR 2015000038W WO 2016126217 A1 WO2016126217 A1 WO 2016126217A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- composition according
- zinc
- benzydamine
- quaternary ammonium
- Prior art date
Links
- CNBGNNVCVSKAQZ-UHFFFAOYSA-N benzydamine Chemical compound C12=CC=CC=C2C(OCCCN(C)C)=NN1CC1=CC=CC=C1 CNBGNNVCVSKAQZ-UHFFFAOYSA-N 0.000 title claims description 37
- 229960000333 benzydamine Drugs 0.000 title claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 230000002421 anti-septic effect Effects 0.000 claims abstract description 19
- 239000003589 local anesthetic agent Substances 0.000 claims abstract description 11
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims abstract description 10
- 150000003751 zinc Chemical class 0.000 claims abstract description 10
- HNNIWKQLJSNAEQ-UHFFFAOYSA-N Benzydamine hydrochloride Chemical compound Cl.C12=CC=CC=C2C(OCCCN(C)C)=NN1CC1=CC=CC=C1 HNNIWKQLJSNAEQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229960001689 benzydamine hydrochloride Drugs 0.000 claims abstract description 7
- NEUSVAOJNUQRTM-UHFFFAOYSA-N cetylpyridinium Chemical compound CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NEUSVAOJNUQRTM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229960004830 cetylpyridinium Drugs 0.000 claims abstract description 6
- 229960004393 lidocaine hydrochloride Drugs 0.000 claims abstract 2
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 claims abstract 2
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 claims description 19
- 229960001927 cetylpyridinium chloride Drugs 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 11
- 229960004194 lidocaine Drugs 0.000 claims description 10
- 201000007100 Pharyngitis Diseases 0.000 claims description 9
- 239000007937 lozenge Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 5
- 238000005550 wet granulation Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
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- 230000000063 preceeding effect Effects 0.000 claims 4
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- 238000002360 preparation method Methods 0.000 abstract description 5
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 9
- 239000011701 zinc Substances 0.000 description 9
- 229910052725 zinc Inorganic materials 0.000 description 9
- 208000002193 Pain Diseases 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000007794 irritation Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 206010068319 Oropharyngeal pain Diseases 0.000 description 3
- 230000003444 anaesthetic effect Effects 0.000 description 3
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- -1 cationic quaternary ammonium compound Chemical class 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
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- 208000007565 gingivitis Diseases 0.000 description 3
- 230000004968 inflammatory condition Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
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- 230000000699 topical effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000011787 zinc oxide Substances 0.000 description 3
- 235000014692 zinc oxide Nutrition 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- 208000005232 Glossitis Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
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- 239000012530 fluid Substances 0.000 description 2
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- 239000006186 oral dosage form Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000007483 tonsillectomy Methods 0.000 description 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- WFJIVOKAWHGMBH-UHFFFAOYSA-N 4-hexylbenzene-1,3-diol Chemical compound CCCCCCC1=CC=C(O)C=C1O WFJIVOKAWHGMBH-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 206010028034 Mouth ulceration Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 201000010927 Mucositis Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 206010065016 Post-traumatic pain Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010043183 Teething Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010047473 Viral pharyngitis Diseases 0.000 description 1
- FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 description 1
- CANRESZKMUPMAE-UHFFFAOYSA-L Zinc lactate Chemical compound [Zn+2].CC(O)C([O-])=O.CC(O)C([O-])=O CANRESZKMUPMAE-UHFFFAOYSA-L 0.000 description 1
- 239000004110 Zinc silicate Substances 0.000 description 1
- 239000005083 Zinc sulfide Substances 0.000 description 1
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
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- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
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- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 208000002399 aphthous stomatitis Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960000386 benzocaine hydrochloride Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940105847 calamine Drugs 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- KNZADIMHVBBPOA-UHFFFAOYSA-N dyclonine hydrochloride Chemical compound [Cl-].C1=CC(OCCCC)=CC=C1C(=O)CC[NH+]1CCCCC1 KNZADIMHVBBPOA-UHFFFAOYSA-N 0.000 description 1
- 229960003462 dyclonine hydrochloride Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- MFGZXPGKKJMZIY-UHFFFAOYSA-N ethyl 5-amino-1-(4-sulfamoylphenyl)pyrazole-4-carboxylate Chemical compound NC1=C(C(=O)OCC)C=NN1C1=CC=C(S(N)(=O)=O)C=C1 MFGZXPGKKJMZIY-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
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- 229910052864 hemimorphite Inorganic materials 0.000 description 1
- 229960003258 hexylresorcinol Drugs 0.000 description 1
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical class Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
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- 230000001225 therapeutic effect Effects 0.000 description 1
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- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229940072358 xylocaine Drugs 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 239000011667 zinc carbonate Substances 0.000 description 1
- 235000004416 zinc carbonate Nutrition 0.000 description 1
- 229910000010 zinc carbonate Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011746 zinc citrate Substances 0.000 description 1
- 235000006076 zinc citrate Nutrition 0.000 description 1
- 229940068475 zinc citrate Drugs 0.000 description 1
- SRWMQSFFRFWREA-UHFFFAOYSA-M zinc formate Chemical compound [Zn+2].[O-]C=O SRWMQSFFRFWREA-UHFFFAOYSA-M 0.000 description 1
- 239000011576 zinc lactate Substances 0.000 description 1
- 235000000193 zinc lactate Nutrition 0.000 description 1
- 229940050168 zinc lactate Drugs 0.000 description 1
- XSMMCTCMFDWXIX-UHFFFAOYSA-N zinc silicate Chemical compound [Zn+2].[O-][Si]([O-])=O XSMMCTCMFDWXIX-UHFFFAOYSA-N 0.000 description 1
- 235000019352 zinc silicate Nutrition 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 229910052984 zinc sulfide Inorganic materials 0.000 description 1
- 229940006174 zinc valerate Drugs 0.000 description 1
- VRGNUPCISFMPEM-ZVGUSBNCSA-L zinc;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Zn+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VRGNUPCISFMPEM-ZVGUSBNCSA-L 0.000 description 1
- LPEBYPDZMWMCLZ-CVBJKYQLSA-L zinc;(z)-octadec-9-enoate Chemical compound [Zn+2].CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O LPEBYPDZMWMCLZ-CVBJKYQLSA-L 0.000 description 1
- ZNVKGUVDRSSWHV-UHFFFAOYSA-L zinc;4-hydroxybenzenesulfonate Chemical compound [Zn+2].OC1=CC=C(S([O-])(=O)=O)C=C1.OC1=CC=C(S([O-])(=O)=O)C=C1 ZNVKGUVDRSSWHV-UHFFFAOYSA-L 0.000 description 1
- MFMKGXZULQONRI-UHFFFAOYSA-L zinc;diiodate Chemical compound [Zn+2].[O-]I(=O)=O.[O-]I(=O)=O MFMKGXZULQONRI-UHFFFAOYSA-L 0.000 description 1
- CPYIZQLXMGRKSW-UHFFFAOYSA-N zinc;iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+3].[Fe+3].[Zn+2] CPYIZQLXMGRKSW-UHFFFAOYSA-N 0.000 description 1
- CHJMFFKHPHCQIJ-UHFFFAOYSA-L zinc;octanoate Chemical compound [Zn+2].CCCCCCCC([O-])=O.CCCCCCCC([O-])=O CHJMFFKHPHCQIJ-UHFFFAOYSA-L 0.000 description 1
- ZPEJZWGMHAKWNL-UHFFFAOYSA-L zinc;oxalate Chemical compound [Zn+2].[O-]C(=O)C([O-])=O ZPEJZWGMHAKWNL-UHFFFAOYSA-L 0.000 description 1
- BUDAIZWUWHWZPQ-UHFFFAOYSA-L zinc;pentanoate Chemical compound [Zn+2].CCCCC([O-])=O.CCCCC([O-])=O BUDAIZWUWHWZPQ-UHFFFAOYSA-L 0.000 description 1
- XDWXRAYGALQIFG-UHFFFAOYSA-L zinc;propanoate Chemical compound [Zn+2].CCC([O-])=O.CCC([O-])=O XDWXRAYGALQIFG-UHFFFAOYSA-L 0.000 description 1
- DRDVZXDWVBGGMH-UHFFFAOYSA-N zinc;sulfide Chemical compound [S-2].[Zn+2] DRDVZXDWVBGGMH-UHFFFAOYSA-N 0.000 description 1
- AMHNZOICSMBGDH-UHFFFAOYSA-L zineb Chemical compound [Zn+2].[S-]C(=S)NCCNC([S-])=S AMHNZOICSMBGDH-UHFFFAOYSA-L 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4425—Pyridinium derivatives, e.g. pralidoxime, pyridostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to the stable pharmaceutical compositions containing benzydamine hydrochloride as an anti-inflammatory agent, an quaternary ammonium compound of antiseptics, a local anesthetic agent and optionally zinc salt.
- sore throats are caused cold and viruses. Some sore throats can be caused by infection by bacteria. Antibiotics is rarely required in some cases. Viral sore throats, on the other hand, do not respond to antibiotics, and therefore management of the symptoms is required until the virus has been eliminated by the body.
- Sore throat products are available as lozenges, sprays, gargles, and, most recently, pain strips that are applied directly to the tongue, providing immediate pain relief.
- These agents usually contain anesthetics, such as benzocaine and dyclonine hydrochloride, which provide temporary relief.
- Other products available contain local antiseptics, such as cetylpyridinium chloride, hexylresorcinol, and/or menthol or camphor. Some products also may contain phenol.
- Benzydamine is a locally acting anesthetic and analgesic drug. It is used for gingivitis, stomatitis, glossitis apthous ulcers, dental surgery and oral ulceration due to radiation therapy, pharyngitis, tonsillitis, post tonsillectomy radiation or intubation mucositis.
- Benzydamine has analgesic, antipyretic, and anti-inflammatory effects.
- Benzydamine hydrochloride is painkiller medicine utilized to relieve mild to moderate pain and inflammation in a particular area. If it directly applied to the affected area, it can be very effective.
- Benzydamine also works by preventing the formation of prostaglandins.
- topically applied benzydamine is effective in attenuating a variety of inflammatory conditions including oral mucositis induced by antineoplastic radiation or chemotherapy.
- Antiseptics can be used for handwashing, pre-operative skin disinfection, mucous membrane disinfection, preventing and treating infected wounds and burns, treating mouth and throat infections.
- Antiseptics can be classified according to their chemical structure. Commonly used antiseptic groups are alcohols, quaternary ammonium compounds, chlorhexidine and other diguanides, antibacterial dyes, chlorine and hypochlorites, inorganic iodine compounds, metals, peroxides and permanganates, halogenated phenol derivatives and quinolone derivatives. Cetylpyridinium chloride is a member of quaternary ammonium compounds.
- Cetylpyridinium chemical name is 1-Hexadecylpyridinium, is a cationic bactericidal surfactant used as a topical antiseptic for skin.
- Cetylpyridinium chloride can be purchased in two forms: cetylpyridinium chloride and cetylpyridinium chloride monohydrate. Cetylpyridinium chloride is commonly used in oral rinses for cleaning mouth and treating throat or mouth infections and teething problems.
- Cetylpyridinium chloride is a cationic quaternary ammonium compound that is known to have antibacterial properties and helps fight plaque and gingivitis. Cetylpyridinium chloride has a combination of antibacterial and anti-fungal activity.
- Cetylpyridinium is a topical antiseptic for skin, wounds, mucous membranes, instruments. It is used in solutions or lozenges for the treatment of minor infections of the mouth and throat depending antiseptic properties.
- Local anesthetics have been used in the aim of having a local analgesic effect, including absence of pain sensation for many years. Local anesthetics can be used for acute and chronic pain, also industry of surgery, podiatry and dentistry.
- Lidocaine chemical name is (1 E)-2-(Diethylamino)-N-(2,6-dimethylphenyl)ethanimidic acid, is also called xylocaine or lignocaine.
- Zinc is a metal that is called an "essential trace element" because very small amounts of zinc are necessary for human health. It can be used for boosting the immune system, treating the common cold and recurrent ear infections, and preventing lower respiratory infections. Also zinc is used for malaria and other diseases caused by parasites.
- Zinc salts is applied to the skin for treating acne, aging skin, herpes simplex infections, and to speed wound healing.
- Zinc preparation can be sprayed in the nostrils for treating the common cold.
- EP 0812193 relates to the oral hygiene compositions containing an anti-inflammatory agent; benzydamine and a anti-microbial agent; cetyl pyridinium chloride and having improved antimicrobial activity.
- composition of the invention may contain benzydamine and cetyl pyridinium chloride in the ratio (by weight) of from 10:1 to 1 :10.
- EP0759739 describes a method of adding chemotherapeutic preparations including cetylpyridinium chloride and lidocaine to dental containing several bundles comprising multiple fibres.
- EP2570123 there is provided the use of one or more anti-bacterial compounds including cetylpyridinium chloride and lidocaine for the preparation of a medicament wherein the one or more anti-bacterial compounds exhibits an anaesthetic effect.
- the present invention provides pharmaceutical formulations comprising active ingredients combination characterized by 1.) good stability properties, 2.) controlling the release of the active ingredient according to desired therapeutical needs, and finally 3.) simple and also competitive manufacturing process.
- the major subject of the present invention is to provide a formulation which has resistant against physical and environmental conditions and also have a high bioavailability.
- composition characterized in that it comprises:
- benzydamine, lidocaine and also a zinc salt may be effectively combined with cetylpyridinium chloride, comparing with single activity of benzydamine and with an enhancement of the activity of cetylpyridinium chloride and other compounds, so as to provide an effective antiseptic, anti-inflammatory and analgesic treatment.
- cetylpyridinium chloride comparing with single activity of benzydamine and with an enhancement of the activity of cetylpyridinium chloride and other compounds, so as to provide an effective antiseptic, anti-inflammatory and analgesic treatment.
- This invention is related to a pharmaceutical product that contains a local anesthetic called lidocaine or its salts, which relieves pain and irritation; and nonsteroidal anti-inflammatory agent called benzydamine or its salts in anti-inflammatory treatment for the relief of painful inflammatory conditions of the mouth; and an antiseptic called cetylpyridinium chloride, which kills bacteria and helps prevent infection.
- a local anesthetic called lidocaine or its salts
- benzydamine or its salts in anti-inflammatory treatment for the relief of painful inflammatory conditions of the mouth
- an antiseptic called cetylpyridinium chloride
- a preferred embodiment according to the present invention relates to a pharmaceutical composition, characterized in that it comprises:
- a) active ingredient selected from nonsteroidal anti-inflammatory agents is benzydamine hydrochloride,
- active ingredient selected from quaternary ammonium compound of antiseptics is cetylpyridinium chloride
- active ingredient selected from local anesthetic agents is lidocaine
- Benzydamine may be used as a pharmaceutically acceptable salt thereof, for example benzydamine hydrochloride.
- Cetylpyridinium may be used as a pharmaceutically acceptable salt thereof, for example cetylpyridinium chloride.
- zinc means a compound including, but not limited to; zinc,zinc acetate, zinc bromide, zinc caprylate, zinc carbonate, zinc chloride, zinc citrate, zinc formate, zinc hexafluorosilicate, zinc iodate, zinc iodide, zinc iodide-starch, zinc lactate, zinc nitrate, zinc oleate, zinc oxalate, zinc oxide, calamine (zinc oxide with a small proportion of ferric oxide), zinc p-phenolsulfonate, zinc propionate, zinc salicylate, zinc silicate, zinc stearate, zinc sulfate, zinc sulfide, zinc tarmate, zinc tartrate, zinc valerate, zinc ethylenebis(dithiocarbamate), poly(zinc acryfate) or a combination thereof and their pharmaceutically acceptable salts.
- the formulation according to the present invention may be in the form of lozenge and other solid oral dosage forms or liquid oral dosage forms.
- the preferred dosage form according to the present invention is the solid dosage form, preferably a tablet or lozenge form.
- Lozenges are the most commonly used OTC products for the treatment of sore throat pain. There are 3 main types: lozenges with a weak topical anesthetic, lozenges with menthol, and unmeditated lozenges.
- composition of the present invention may comprise one or more pharmaceutically acceptable excipient(s).
- Pharmaceutically acceptable excipients comprise, but are not limited to, fillers, disintegrants, binders, lubricants, glidants, sweeteners, aromatic agents, preservatives, coloring agents, and the mixtures thereof, to facilitate the physical formulation of various dosage forms like orally disintegrating tablets, chewable tablets and suspensions (including dry powders or granules for suspension).
- a preferred embodiment according to the present invention provides a method for preparing pharmaceutical granules in wet granulation, comprising the steps of
- Benzydamine hydrochloride an quaternary ammonium compound of antiseptics, a local anesthetic agent, optionally a zinc salt and excipients are mixed with a binder solution comprising PVP, ethanol or water or a combination thereof,
- a further preferred embodiment according to the present invention provides a method for preparing pharmaceutical granules in wet granulation, comprising the steps of
- benzydamine HCI, cetylpyridinium chloride, lidocaine and optionally a zinc salt and excipients are mixed with a binder solution comprising PVP, ethanol or water or a combination thereof, b. after wet granulation process, next steps are fluid bed drying, sieving and finally blend is obtained,
- compositions of this invention may be used in therapy or as a prophylatic against microbial infections accompanied by irritation, such as skin infections.
- composition can be used for oral application: as an antiseptic, anti-inflammatory and analgesic treatment of gums, mouth and throat, especially for treatment of plaque, gingivitis and periodontitis, denture irritation. It is useful for treating sore or bacteria infected throat, cough-irritated sore throat, and other oral ailments wherein the source of irritation is partly or wholly derived from microbial infection.
- pharyngitis eg following tonsillectomy
- aphthous ulcers e.g following tonsillectomy
- aspecific odontostomatoligic affections e.g following glossitis and stomatitis
- teeting troubles pain and may be used before and/or after dental extractions.
- Intra-granular powders are weighed and mixed, and optionally a zinc salt is added in a pharmaceutically effective amount.
- Binder solution is prepared by adding PVP K30 to water, 3. Dry mix of Step 1 is granulated with binder of step 2 and granules are dried.
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- General Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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Abstract
The present invention relates to the preparation of stable pharmaceutical compositions comprising benzydamine hydrochloride as an anti-inflammatory agent, cetylpyridinium as an quaternary ammonium compound of antiseptics, lidocaine hydrochloride as a local anesthetic agent and optionally a zinc salt.
Description
STABLE PHARMACEUTICAL COMBINATION CONTAINING BENZYDAMINE
Field of invention
The present invention relates to the stable pharmaceutical compositions containing benzydamine hydrochloride as an anti-inflammatory agent, an quaternary ammonium compound of antiseptics, a local anesthetic agent and optionally zinc salt.
Background of the invention
Most sore throats are caused cold and viruses. Some sore throats can be caused by infection by bacteria. Antibiotics is rarely required in some cases. Viral sore throats, on the other hand, do not respond to antibiotics, and therefore management of the symptoms is required until the virus has been eliminated by the body.
Sore throat products are available as lozenges, sprays, gargles, and, most recently, pain strips that are applied directly to the tongue, providing immediate pain relief. These agents usually contain anesthetics, such as benzocaine and dyclonine hydrochloride, which provide temporary relief. Other products available contain local antiseptics, such as cetylpyridinium chloride, hexylresorcinol, and/or menthol or camphor. Some products also may contain phenol.
Benzydamine is a locally acting anesthetic and analgesic drug. It is used for gingivitis, stomatitis, glossitis apthous ulcers, dental surgery and oral ulceration due to radiation therapy, pharyngitis, tonsillitis, post tonsillectomy radiation or intubation mucositis.
Benzydamine has analgesic, antipyretic, and anti-inflammatory effects. Benzydamine hydrochloride is painkiller medicine utilized to relieve mild to moderate pain and inflammation in a particular area. If it directly applied to the affected area, it can be very effective. Benzydamine also works by preventing the formation of prostaglandins.
It is used to reduce post-surgical and post-traumatic pain and edema and to promote healing. It is also used topically in treatment of rheumatic diseases and inflammation of the mouth and throat.
Several clinical studies suggest that topically applied benzydamine is effective in attenuating a variety of inflammatory conditions including oral mucositis induced by antineoplastic radiation or chemotherapy.
The preparation of benzydamine is described in US 3318905. Chemical name is 3-[(1-Benzyl- 1H-indazol-3-yl)oxy]-N,N-dimethyl-1-propanamine. There have been proposals to use benzydamine in mouth washes in many sources.
l
Antiseptics can be used for handwashing, pre-operative skin disinfection, mucous membrane disinfection, preventing and treating infected wounds and burns, treating mouth and throat infections.
Antiseptics can be classified according to their chemical structure. Commonly used antiseptic groups are alcohols, quaternary ammonium compounds, chlorhexidine and other diguanides, antibacterial dyes, chlorine and hypochlorites, inorganic iodine compounds, metals, peroxides and permanganates, halogenated phenol derivatives and quinolone derivatives. Cetylpyridinium chloride is a member of quaternary ammonium compounds.
Cetylpyridinium, chemical name is 1-Hexadecylpyridinium, is a cationic bactericidal surfactant used as a topical antiseptic for skin. Cetylpyridinium chloride can be purchased in two forms: cetylpyridinium chloride and cetylpyridinium chloride monohydrate. Cetylpyridinium chloride is commonly used in oral rinses for cleaning mouth and treating throat or mouth infections and teething problems.
Cetylpyridinium chloride is a cationic quaternary ammonium compound that is known to have antibacterial properties and helps fight plaque and gingivitis. Cetylpyridinium chloride has a combination of antibacterial and anti-fungal activity.
Cetylpyridinium is a topical antiseptic for skin, wounds, mucous membranes, instruments. It is used in solutions or lozenges for the treatment of minor infections of the mouth and throat depending antiseptic properties.
Benzydamine Cetylpyridinium Lidocaine
Local anesthetics have been used in the aim of having a local analgesic effect, including absence of pain sensation for many years. Local anesthetics can be used for acute and chronic pain, also industry of surgery, podiatry and dentistry.
Lidocaine, chemical name is (1 E)-2-(Diethylamino)-N-(2,6-dimethylphenyl)ethanimidic acid, is also called xylocaine or lignocaine.
Zinc is a metal that is called an "essential trace element" because very small amounts of zinc are necessary for human health. It can be used for boosting the immune system, treating the
common cold and recurrent ear infections, and preventing lower respiratory infections. Also zinc is used for malaria and other diseases caused by parasites.
Zinc salts is applied to the skin for treating acne, aging skin, herpes simplex infections, and to speed wound healing. Zinc preparation can be sprayed in the nostrils for treating the common cold.
EP 0812193 relates to the oral hygiene compositions containing an anti-inflammatory agent; benzydamine and a anti-microbial agent; cetyl pyridinium chloride and having improved antimicrobial activity. This document is relevant to provide an effective antiseptic, anti-inflammatory and analgesic treatment for microbial infections in suitable forms of the gum, mouth and throat. According to this document, composition of the invention may contain benzydamine and cetyl pyridinium chloride in the ratio (by weight) of from 10:1 to 1 :10.
EP0759739 describes a method of adding chemotherapeutic preparations including cetylpyridinium chloride and lidocaine to dental containing several bundles comprising multiple fibres.
According to EP2570123, there is provided the use of one or more anti-bacterial compounds including cetylpyridinium chloride and lidocaine for the preparation of a medicament wherein the one or more anti-bacterial compounds exhibits an anaesthetic effect.
Summary of the invention
The present invention provides pharmaceutical formulations comprising active ingredients combination characterized by 1.) good stability properties, 2.) controlling the release of the active ingredient according to desired therapeutical needs, and finally 3.) simple and also competitive manufacturing process.
The major subject of the present invention is to provide a formulation which has resistant against physical and environmental conditions and also have a high bioavailability.
Pharmaceutical composition, characterized in that it comprises:
a) Benzydamine or pharmaceutical acceptable salt thereof as nonsteroidal antiinflammatory agent,
b) a quaternary ammonium compound of antiseptic,
c) a local anesthetic agent,
d) optionally a zinc salt,
We have now surprisingly found that benzydamine, lidocaine and also a zinc salt may be effectively combined with cetylpyridinium chloride, comparing with single activity of benzydamine and with an enhancement of the activity of cetylpyridinium chloride and other compounds, so as to provide an effective antiseptic, anti-inflammatory and analgesic treatment.
Detailed description of the invention
This invention is related to a pharmaceutical product that contains a local anesthetic called lidocaine or its salts, which relieves pain and irritation; and nonsteroidal anti-inflammatory agent called benzydamine or its salts in anti-inflammatory treatment for the relief of painful inflammatory conditions of the mouth; and an antiseptic called cetylpyridinium chloride, which kills bacteria and helps prevent infection.
A preferred embodiment according to the present invention relates to a pharmaceutical composition, characterized in that it comprises:
a) active ingredient selected from nonsteroidal anti-inflammatory agents is benzydamine hydrochloride,
b) active ingredient selected from quaternary ammonium compound of antiseptics is cetylpyridinium chloride,
c) active ingredient selected from local anesthetic agents is lidocaine,
d) optionally a zinc salt,
in combination with at least one pharmaceutically acceptable excipient.
Benzydamine may be used as a pharmaceutically acceptable salt thereof, for example benzydamine hydrochloride.
Cetylpyridinium may be used as a pharmaceutically acceptable salt thereof, for example cetylpyridinium chloride.
In this invention, the term " zinc" means a compound including, but not limited to; zinc,zinc acetate, zinc bromide, zinc caprylate, zinc carbonate, zinc chloride, zinc citrate, zinc formate, zinc hexafluorosilicate, zinc iodate, zinc iodide, zinc iodide-starch, zinc lactate, zinc nitrate, zinc oleate, zinc oxalate, zinc oxide, calamine (zinc oxide with a small proportion of ferric oxide), zinc p-phenolsulfonate, zinc propionate, zinc salicylate, zinc silicate, zinc stearate, zinc sulfate, zinc sulfide, zinc tarmate, zinc tartrate, zinc valerate, zinc ethylenebis(dithiocarbamate), poly(zinc acryfate) or a combination thereof and their pharmaceutically acceptable salts.
The formulation according to the present invention may be in the form of lozenge and other solid oral dosage forms or liquid oral dosage forms. The preferred dosage form according to the present invention is the solid dosage form, preferably a tablet or lozenge form.
Lozenges are the most commonly used OTC products for the treatment of sore throat pain. There are 3 main types: lozenges with a weak topical anesthetic, lozenges with menthol, and unmeditated lozenges.
Pharmaceutical composition of the present invention may comprise one or more pharmaceutically acceptable excipient(s). Pharmaceutically acceptable excipients comprise, but are not limited to, fillers, disintegrants, binders, lubricants, glidants, sweeteners, aromatic agents, preservatives, coloring agents, and the mixtures thereof, to facilitate the physical
formulation of various dosage forms like orally disintegrating tablets, chewable tablets and suspensions (including dry powders or granules for suspension).
A preferred embodiment according to the present invention provides a method for preparing pharmaceutical granules in wet granulation, comprising the steps of
a. Benzydamine hydrochloride, an quaternary ammonium compound of antiseptics, a local anesthetic agent, optionally a zinc salt and excipients are mixed with a binder solution comprising PVP, ethanol or water or a combination thereof,
b. after wet granulation process, next steps are fluid bed drying, sieving and finally blend is obtained,
c. obtained blend is mixed with sweetener or flavour agents,
d. lubricating the final blend of step c,
e. compressing the mixture into tablets.
A further preferred embodiment according to the present invention provides a method for preparing pharmaceutical granules in wet granulation, comprising the steps of
a. benzydamine HCI, cetylpyridinium chloride, lidocaine and optionally a zinc salt and excipients are mixed with a binder solution comprising PVP, ethanol or water or a combination thereof, b. after wet granulation process, next steps are fluid bed drying, sieving and finally blend is obtained,
c. obtained blend is mixed with sweetener or flavour agents,
d. lubricating the final blend of step c,
e. compressing the mixture into tablets.
Compositions of this invention may be used in therapy or as a prophylatic against microbial infections accompanied by irritation, such as skin infections. In particular, composition can be used for oral application: as an antiseptic, anti-inflammatory and analgesic treatment of gums, mouth and throat, especially for treatment of plaque, gingivitis and periodontitis, denture irritation. It is useful for treating sore or bacteria infected throat, cough-irritated sore throat, and other oral ailments wherein the source of irritation is partly or wholly derived from microbial infection. It may be used for painful inflammatory conditions of the mouth and throat including pharyngitis (eg following tonsillectomy), aphthous ulcers, aspecific odontostomatoligic affections, glossitis and stomatitis, and teeting troubles, pain and may be used before and/or after dental extractions.
Examples
The manufacturing method of Examples 1 and 2 are described below:
1. Intra-granular powders are weighed and mixed, and optionally a zinc salt is added in a pharmaceutically effective amount.
2. Binder solution is prepared by adding PVP K30 to water,
3. Dry mix of Step 1 is granulated with binder of step 2 and granules are dried.
4. Then dried granules are shifted through 1.0 mm mesh.
5. According to yield, extragranular materials are weighed and shifted and added to dried shifted granules and blended for 5 min.
6. Then lubricant is weighed and shifted and added to above step and lubricated for 3 min and finally resulting powder is compressed.
Claims
1. A pharmaceutical composition, characterized in that it comprises:
a) Benzydamine or pharmaceutical acceptable salt thereof as nonsteroidal antiinflammatory agent,
b) a quaternary ammonium compound of antiseptic,
c) a local anesthetic agent,
d) optionally a zinc salt,
in combination with at least one pharmaceutically acceptable excipient.
2. A pharmaceutical composition according to claim 1, wherein the nonsteroidal anti- inflammatory drug is benzydamine hydrochloride.
3. A pharmaceutical composition according to claims 1-2, wherein quaternary ammonium compound of antiseptic drug is cetylpyridinium and/or pharmaceutically acceptable salts thereof.
4. A pharmaceutical composition according to claim 3, wherein quaternary ammonium compound of antiseptic drug is cetylpyridinium chloride.
5. A pharmaceutical composition according to claims 1-4, wherein local anesthetic drug is lidocaine and/or pharmaceutically acceptable salts thereof.
6. A pharmaceutical composition according to claim 5, wherein local anesthetic drug is lidocaine hydrochloride.
7. A pharmaceutical composition according to any one of the preceeding claims, wherein the pharmaceutical composition is solid dosage form.
8. A pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is tablet or lozenge.
9. A pharmaceutical composition according to any one of the preceeding claims, wherein the pharmaceutical composition is prepared by wet granulation.
10. A pharmaceutical composition according to any one of the preceeding claims, wherein all active ingredients are in the internal phase of composition.
11. A pharmaceutical composition according to any one of the preceeding claims, for use in the treatment of mouth ulcers and sore throats.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2015/000038 WO2016126217A1 (en) | 2015-02-03 | 2015-02-03 | Stable pharmaceutical combination containing benzydamine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2015/000038 WO2016126217A1 (en) | 2015-02-03 | 2015-02-03 | Stable pharmaceutical combination containing benzydamine |
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| WO2016126217A1 true WO2016126217A1 (en) | 2016-08-11 |
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| PCT/TR2015/000038 WO2016126217A1 (en) | 2015-02-03 | 2015-02-03 | Stable pharmaceutical combination containing benzydamine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2741388C1 (en) * | 2020-08-06 | 2021-01-25 | Закрытое акционерное общество "АФОФАРМ" (ЗАО "АФОФАРМ") | Medicinal preparation in the form of tablets for prevention and / or treatment of catarrhal, acute respiratory and other infectious-inflammatory diseases of throat and oral cavity |
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| US3318905A (en) | 1963-08-09 | 1967-05-09 | Acraf | 1-substituted 3-dialkylaminoalkoxy-in-dazoles and 1-substituted-3-hydroxyindazoles |
| EP0759739A1 (en) | 1994-05-10 | 1997-03-05 | Whitehill Oral Technologies Inc. | Improvements in dental floss |
| EP0812193A1 (en) | 1995-02-28 | 1997-12-17 | Smithkline Beecham Farmaceutici S.p.A. | Pharmaceutical compositions containing a benzydamine or its salt and an antimicrobial agent |
| WO2003089007A1 (en) * | 2002-04-22 | 2003-10-30 | Adcock Ingram Intellectual Property (Proprietary) Limited | Pharmaceutical compositions comprising a decongenstant and further active ingredients for treating cough and flu |
| WO2009106963A2 (en) * | 2008-02-26 | 2009-09-03 | Italmed S.R.L. | Dental composition for preventing and treating stomatitis and mouth ulcers |
| WO2010020772A2 (en) * | 2008-08-22 | 2010-02-25 | Reckitt Benckiser Healthcare (Uk) Limited | Improvements in or relating to compositions |
| EP2570123A1 (en) | 2007-11-15 | 2013-03-20 | Reckitt Benckiser Healthcare (UK) Limited | Use of 2,4-dichlorobenzyl alcohol having an anaesthetic effect |
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| EP0759739A1 (en) | 1994-05-10 | 1997-03-05 | Whitehill Oral Technologies Inc. | Improvements in dental floss |
| EP0812193A1 (en) | 1995-02-28 | 1997-12-17 | Smithkline Beecham Farmaceutici S.p.A. | Pharmaceutical compositions containing a benzydamine or its salt and an antimicrobial agent |
| EP0812193B1 (en) * | 1995-02-28 | 2002-10-16 | GlaxoSmithKline S.p.A. | Pharmaceutical compositions containing a benzydamine or its salt and an antimicrobial agent |
| WO2003089007A1 (en) * | 2002-04-22 | 2003-10-30 | Adcock Ingram Intellectual Property (Proprietary) Limited | Pharmaceutical compositions comprising a decongenstant and further active ingredients for treating cough and flu |
| EP2570123A1 (en) | 2007-11-15 | 2013-03-20 | Reckitt Benckiser Healthcare (UK) Limited | Use of 2,4-dichlorobenzyl alcohol having an anaesthetic effect |
| WO2009106963A2 (en) * | 2008-02-26 | 2009-09-03 | Italmed S.R.L. | Dental composition for preventing and treating stomatitis and mouth ulcers |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2741388C1 (en) * | 2020-08-06 | 2021-01-25 | Закрытое акционерное общество "АФОФАРМ" (ЗАО "АФОФАРМ") | Medicinal preparation in the form of tablets for prevention and / or treatment of catarrhal, acute respiratory and other infectious-inflammatory diseases of throat and oral cavity |
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