CN104586888A - Pharmaceutical composition for treating periodontitis and method for preparing pharmaceutical composition for treating periodontitis - Google Patents
Pharmaceutical composition for treating periodontitis and method for preparing pharmaceutical composition for treating periodontitis Download PDFInfo
- Publication number
- CN104586888A CN104586888A CN201410843035.1A CN201410843035A CN104586888A CN 104586888 A CN104586888 A CN 104586888A CN 201410843035 A CN201410843035 A CN 201410843035A CN 104586888 A CN104586888 A CN 104586888A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- plga
- iodine
- periodontitis
- lactide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 201000001245 periodontitis Diseases 0.000 title claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title description 9
- 239000003814 drug Substances 0.000 claims abstract description 40
- 238000011282 treatment Methods 0.000 claims abstract description 30
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 13
- 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 claims abstract description 10
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims abstract description 10
- OKJPEAGHQZHRQV-UHFFFAOYSA-N iodoform Chemical compound IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 claims abstract description 10
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 229960002233 benzalkonium bromide Drugs 0.000 claims abstract description 6
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims abstract description 6
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 claims abstract description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 5
- 229920000153 Povidone-iodine Polymers 0.000 claims abstract description 5
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229960000686 benzalkonium chloride Drugs 0.000 claims abstract description 5
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims abstract description 5
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 claims abstract description 5
- 229960001621 povidone-iodine Drugs 0.000 claims abstract description 5
- 229910052709 silver Inorganic materials 0.000 claims abstract description 5
- 239000004332 silver Substances 0.000 claims abstract description 5
- 229910001961 silver nitrate Inorganic materials 0.000 claims abstract description 5
- 230000002195 synergetic effect Effects 0.000 claims abstract description 5
- 229960003500 triclosan Drugs 0.000 claims abstract description 5
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 25
- 239000002671 adjuvant Substances 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000000758 substrate Substances 0.000 claims description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 6
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 claims description 6
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 4
- 229930182843 D-Lactic acid Natural products 0.000 claims description 4
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 claims description 4
- OJIYIVCMRYCWSE-UHFFFAOYSA-M Domiphen bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 OJIYIVCMRYCWSE-UHFFFAOYSA-M 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 229940022769 d- lactic acid Drugs 0.000 claims description 4
- CIKWKGFPFXJVGW-UHFFFAOYSA-N ethacridine Chemical compound C1=C(N)C=CC2=C(N)C3=CC(OCC)=CC=C3N=C21 CIKWKGFPFXJVGW-UHFFFAOYSA-N 0.000 claims description 4
- 229960001588 ethacridine Drugs 0.000 claims description 4
- 229960000349 nitrofural Drugs 0.000 claims description 4
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 4
- 229920000151 polyglycol Polymers 0.000 claims description 4
- 239000010695 polyglycol Substances 0.000 claims description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 4
- JJTUDXZGHPGLLC-ZXZARUISSA-N (3r,6s)-3,6-dimethyl-1,4-dioxane-2,5-dione Chemical compound C[C@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-ZXZARUISSA-N 0.000 claims description 3
- 229940116333 ethyl lactate Drugs 0.000 claims description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 235000001014 amino acid Nutrition 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 2
- 229940074076 glycerol formal Drugs 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 239000004626 polylactic acid Substances 0.000 claims description 2
- 208000005888 Periodontal Pocket Diseases 0.000 abstract description 25
- 230000000694 effects Effects 0.000 abstract description 9
- 239000000463 material Substances 0.000 abstract description 4
- 239000007788 liquid Substances 0.000 abstract description 3
- 239000007787 solid Substances 0.000 abstract description 2
- 229960003260 chlorhexidine Drugs 0.000 abstract 2
- IYLLULUTZPKQBW-UHFFFAOYSA-N Acrinol Chemical compound CC(O)C(O)=O.C1=C(N)C=CC2=C(N)C3=CC(OCC)=CC=C3N=C21 IYLLULUTZPKQBW-UHFFFAOYSA-N 0.000 abstract 1
- 229960000629 domiphen Drugs 0.000 abstract 1
- YXUPZGKORWTXID-UHFFFAOYSA-N domiphen Chemical compound CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 YXUPZGKORWTXID-UHFFFAOYSA-N 0.000 abstract 1
- 239000011159 matrix material Substances 0.000 abstract 1
- 229960001907 nitrofurazone Drugs 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
- 208000028169 periodontal disease Diseases 0.000 description 13
- 230000003239 periodontal effect Effects 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 10
- 230000003115 biocidal effect Effects 0.000 description 10
- 239000011630 iodine Substances 0.000 description 10
- 229910052740 iodine Inorganic materials 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 239000013642 negative control Substances 0.000 description 8
- 239000013641 positive control Substances 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 6
- YADZBEISHVCBSJ-UHFFFAOYSA-N [I].OCC(O)CO Chemical compound [I].OCC(O)CO YADZBEISHVCBSJ-UHFFFAOYSA-N 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 210000004195 gingiva Anatomy 0.000 description 6
- 229960004023 minocycline Drugs 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 210000000988 bone and bone Anatomy 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000004098 Tetracycline Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 238000002651 drug therapy Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000000214 mouth Anatomy 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 229960002180 tetracycline Drugs 0.000 description 4
- 229930101283 tetracycline Natural products 0.000 description 4
- 235000019364 tetracycline Nutrition 0.000 description 4
- 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
- 206010059866 Drug resistance Diseases 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 244000052616 bacterial pathogen Species 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229960004082 doxycycline hydrochloride Drugs 0.000 description 3
- 210000004283 incisor Anatomy 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 150000003522 tetracyclines Chemical class 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 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 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 206010068052 Mosaicism Diseases 0.000 description 2
- LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 241000656145 Thyrsites atun Species 0.000 description 2
- 229920006221 acetate fiber Polymers 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 229960003722 doxycycline Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 229960000282 metronidazole Drugs 0.000 description 2
- 244000000010 microbial pathogen Species 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229960002800 prednisolone acetate Drugs 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000003765 sex chromosome Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- QJVHTELASVOWBE-AGNWQMPPSA-N (2s,5r,6r)-6-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 QJVHTELASVOWBE-AGNWQMPPSA-N 0.000 description 1
- WTJXVDPDEQKTCV-UHFFFAOYSA-N 4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydron;chloride Chemical compound Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2C1CC1C(N(C)C)C(=O)C(C(N)=O)=C(O)C1(O)C2=O WTJXVDPDEQKTCV-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000031968 Cadaver Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 208000006558 Dental Calculus Diseases 0.000 description 1
- 235000009161 Espostoa lanata Nutrition 0.000 description 1
- 240000001624 Espostoa lanata Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- IPWKIXLWTCNBKN-UHFFFAOYSA-N Madelen Chemical compound CC1=NC=C([N+]([O-])=O)N1CC(O)CCl IPWKIXLWTCNBKN-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 206010072574 Periodontal inflammation Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 description 1
- 206010044029 Tooth deposit Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 229960002152 chlorhexidine acetate Drugs 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000001277 chronic periodontitis Diseases 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000009189 diving Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011841 epidemiological investigation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 201000007119 infective endocarditis Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940063189 metrogel Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 229960002421 minocycline hydrochloride Drugs 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 150000004957 nitroimidazoles Chemical class 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960002313 ornidazole Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 210000002379 periodontal ligament Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000000710 polymer precipitation Methods 0.000 description 1
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
- 210000003314 quadriceps muscle Anatomy 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000009666 routine test Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- -1 tetracycline vinyl acetate Chemical class 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229960005053 tinidazole Drugs 0.000 description 1
- 235000000112 undernutrition Nutrition 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a pharmaceutical composition for treating periodontitis. The pharmaceutical composition comprises a main medicine, matrix auxiliary materials and a solvent, wherein the main medicine is any one of iodine, iodoform, chlorhexidine, chlorhexidine iodine, benzalkonium bromide, benzalkonium chloride, povidone iodine, triclosan, rivanol, furacilin, domiphen, myristylpicolinum bromide, silver nitrate and nanometer silver, or is a mixture of two or more of synergetic main medicines. The pharmaceutical composition disclosed by the invention automatically turns into a semisolid or solid substance with sustained-release effect and slowly releases with the effective treatment medicine amount for 3-6 days when injected into the periodontal pocket of a patient in the liquid form, thereby greatly bringing convenience for the patient to use the pharmaceutical composition and reducing the treatment expense.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of periodontitis and preparation method thereof, belong to field of medicaments, concrete belongs to department of stomatology periodontitis Drug therapy field.
Background technology
One, the harm of periodontitis
periodontitisbe involve four kinds of Periodontal Supporting Tissue (
gingiva,
periodontal membrane, alveolar bone and cementum) chronic infectious disease, often cause the inflammatory destruction of Periodontal Supporting Tissue.Its harm is large, and sickness rate is high, is come to a conclusion as after cancer and cardiovascular and cerebrovascular disease at present in medical circle, and human body health is produced to the third-largest killer of harm, be also oral health " number one killer " simultaneously.
Periodontal disease can cause the infringement of teeth, periodontal, if can not get timely medical treatment, its pathogenic bacterium can arrive each position of health by blood circulation, cause the disease of other Organ and tissues of health.Such as antibacterial coagulation platelet can form thrombosis, and clinical research finds that infective endocarditis and odontogenic infection have substantial connection.The antibacterial causing periodontal local chronic to infect and toxic product thereof can enter in the blood of patient, and these antibacterials and toxic product can increase and increase the weight of arteriosclerosis and thrombosis, make periodontitis become the risk factor of apoplexy generation.Research finds can helicobacter pylori be detected in the saliva of patients with periodontal disease, in subgingival plaque in patient's periodontal pocket, the recall rate of this bacterium is higher, periodontal disease likely increases helicobacter pylori infections as can be seen here, and the increase of the latter can cause the generation of chronic gastritis, gastric ulcer and gastric cancer.Diabetics is high with the Hazard ratio ND of periodontitis, and periodontitis can promote that patient blood glucose raises, therebetween have common genetic base, diabetes also promote the generation of periodontitis by the impact of the function on periodontal flora, neutrophilic granulocyte, inflammatory reaction, organization healing ability.Periodontitis pathogen cell toxin can damage nephron and blood vessel bunch cell, thus kidney is worked the mischief, and the periodontitis prevalence of Patients with Chronic Kidney Disease also can increase, according to Third National oral health epidemiological investigation display, China adult periodontal disease prevalence can reach more than 80%.
Under army corps and special operation environment, periodontitis sickness rate is higher.Officers and men under the special operation environment such as submarine, remote island, due to reasons such as work strain undernutritions, periodontal disease is particularly outstanding.And the crewman of long-time oceangoing voyage due to narrow space on ship, hygienic habit poor, restricted with water, and the reason such as nutritional imbalance, its onset of periodontitis rate is up to 91%.Research finds that ship rocking periodontal disease condition is apparently higher than the diligent personnel of bank, and its reason is on ship rocking long-term work life naval vessels, and because fresh water is limited during oceangoing voyage, shipwreck for toothbrushing is to be protected.All ages and classes, post, schooling ship rocking suffers from periodontal situation also difference, officer is apparently higher than soldier, sergeant, this is obviously longer than young soldier and sergeant due to officer's life-time on naval vessels, makes its periodontitis and gingivitis prevalence showed increased.Also there is certain relation generation and the region of army's periodontal inflammation, the prevalence of rural area officers and men is a little more than city, cities and towns officers and men, not only relevant with personal oral hygiene, depend primarily on guard station ambient water quality comparatively hard, add the ratio that this officers and men suffer from dental calculus, periodontitis.Therefore the healthy of people in periodontal disease serious harm, threatens officers and men and particularly performs the healthy of the officers and men of special duty, cause harmful effect to combat effectiveness of the troops.
Two, periodontitis Current medicine treatment
Periodontal disease is mainly due to the microbial infectious disease that causes a disease, and the major virulent factor of periodontitis is bacterial plaque microorganism.Adopt separately the method removing diseased Root Surfaces tooth maculose clinically, usually can not remove the pathogenic microorganism in periodontal pocket, need to coordinate antibacterial drug therapy could eradicate the cause of disease of periodontal disease.
(1) systemic treatment.Kind difference according to pathogenic bacterium can orally use agents: the 1) compound formulation of the amoxicillin of penicillins, ampicillin or amoxicillin and clavulanic acid; 2) tetracycline, Doxycycline or minocycline; 3) Macrocyclolactone lactone kind medicine azithromycin; 4) nitroimidazoles medicine metronidazole, tinidazole or ornidazole; 5) quinolones; 6) metronidazole and other antibiotic therapeutic alliances.
(2) topical therapeutic.1) tetracycline vinyl acetate fiber controlled release preparation, containing tetracycline 2.5%, can maintain active drug concentration about 10 days in periodontal pocket, because vinyl acetate fiber belongs to non-biodegradation type, needs to take out after 10 days.2) minocycline gel and minocycline microcapsule the former be slow release lipid gel containing 2% minocycline, the latter is the Absorbable rod Microencapsulated Slow system containing 2% minocycline.3) doxycycline hydrochloride gel is containing the gel controlled release agent of 10% doxycycline hydrochloride, can maintain valid density 7 days.4) Metrogel degradable gel shape controlled release agent, drug content 25%, can maintain active drug concentration 1 week after being injected into periodontal pocket.5) the hydrochloric doxycycline 10% of doxycycline hydrochloride situ-gel, is injected in periodontal pocket and can forms semisolid drug-reservoir, and slow releasing medicine about 10 days, is still in conceptual phase.6) iodine glycerol treatment periodontitis.
Three, the deficiency of periodontitis Drug therapy
Compared with topical therapeutic, whole body therapeutic dosage is relatively large, and the dose arriving affected part, local is relatively less, and bioavailability is relatively low, and from the viewpoint of safety and effectiveness, periodontitis local application is more excellent.But no matter be whole body application antibiotic or periodontal pocket topical application antibiotic, all there is following deficiency: 1) antimicrobial spectrum problem: antibiotic has good therapeutical effect to the microbial periodontitis of sensitivity, poor to the curative effect of non-sensitive microbial periodontitis, and the pathogenic bacterium of periodontitis are diversified, there are gram positive bacteria, gram negative bacteria, anaerobe etc.The difference of antibiotic antimicrobial spectrum and periodontitis Pathogen category, makes antibiotic be difficult to meet the Treatment need of periodontitis.2) drug resistance problems: antibiotics resistance sex chromosome mosaicism makes the antibiotic of a lot of anti-microbial property excellence in the past lose antibacterial action gradually, how long can the antibiotic therapeutic effect for the treatment of periodontitis maintain at present?
Iodine glycerol can be used for the treatment of periodontitis, and its shortcoming is: because dosage form is simple, medicine is difficult to be directly used in affected part: in periodontal pocket, and medicine is applied to the curative effect that have impact on medicine outside periodontal band; Iodine glycerol is very fast after smearing to dissipate from affected part, and within one day, need smear for several times, its dosage is inaccurate, easily causes the excessive and corresponding side effect of iodine systemic Absorption.
Summary of the invention
In view of the deficiency of current periodontitis Drug therapy, technical problem to be solved by this invention is, prepares the pharmaceutical preparation of a kind of safe and effective, has a broad antifungal spectrum, the problem that has no drug resistance, treatment periodontitis easy to use, to solve the deficiency of this medicine treatment at present.
After deliberation, iodine has following antibacterial characteristics: fungicidal spectrum is wide, sterilizing ability is strong, and not only to antibacterial, all having very strong inhibitory or killing effect to pathogenic microorganisms such as fungus, spore, viruses, is wide-spectrum bactericide; Not easily producing drug resistance, is a kind of desirable oral care medication.When current antibiotic bacterial resistance sex chromosome mosaicism is day by day serious, iodine is made the treatment that suitable preparation is used for periodontitis, be expected to play good therapeutical effect.The selection of dosage form: according to the Pathophysiology feature of periodontitis and the anatomical structure of periodontal tissue, prepare iodine polymer precipitation situ-gel, liquid preparation quantitatively injects after in periodontal pocket and automatically becomes solid-state or semisolid, this material can adhere to periodontal affected part and discharge medicine slowly, by the rate of release of the proportioning and concentration adjustment medicine that control wherein macromolecular material, make it reach the effect of single administration slow releasing therapeutic dose medicine for 3 ~ 6 days, be all better than conventional formulation iodine glycerol from curative effect, safety, compliance aspect.This dosage form substantially increases the medication compliance of patient, is particularly useful for officers and men, particularly performs the officers and men of special duty, as large-scale water surface naval vessels operating personnel, submarine personnel, diving operation personnel etc.
Therefore, for solving the problem, the technical solution used in the present invention is as follows:
A kind of pharmaceutical composition for the treatment of periodontitis, by principal agent, substrate adjuvant, solvent composition, described principal agent is iodine, in iodoform, hibitane, hibitane iodine, benzalkonium bromide, benzalkonium chloride, povidone iodine, triclosan, ethacridine, nitrofural, oradol, myristylpicolinum bromide, silver nitrate, nanometer silver any one or there is two or more combination synergistic.
A kind of preparation method for the treatment of the pharmaceutical composition of periodontitis, comprise the following steps: principal agent, substrate adjuvant are dissolved in solvent respectively, mix homogeneously, obtain, wherein said principal agent be iodine, in iodoform, hibitane, hibitane iodine, benzalkonium bromide, benzalkonium chloride, povidone iodine, triclosan, ethacridine, nitrofural, oradol, myristylpicolinum bromide, silver nitrate, nanometer silver any one or there is two or more combination synergistic.
Wherein, substrate adjuvant is two or more the mixture in following adjuvant: poly-levorotatory lactide, poly-meso-lactide, PLGA 90/10, PLGA 75/25, PLGA 60/40, PLGA 50/50, end carboxyl polylactic acid, end carboxyl PLGA, D-lactic acid/co-glycolic acid, D-lactic acid/racemic lactic acid copolymer, polyethylene glycol modified polylactide, polyethylene glycol modified polylactide-co-glycolic acid, poly glycol monomethyl ether polydactyl acid, poly glycol monomethyl ether modification PLGA, lactide coglycolide--caprolactone copolymer, lactide--caprolactone copolymer, lactide coglycolide-trimethylene carbonate PLGTmc, polyvinylpyrrolidone, Polyethylene Glycol, the husky nurse of POLO, aminoacid, potassium iodide.
Wherein, substrate adjuvant is: PLGA 50/50, PLGA 75/25 and polyvinylpyrrolidone, and three's mixed weight is than being 20-80:6-35:0.6-13.
Wherein, solvent is METHYLPYRROLIDONE, ethyl acetate, triacetyl glycerine, 2-Pyrrolidone, ethyl lactate, dimethyl sulfoxide, glycerol formal.
Wherein, in compositions, drug content is 0.5%-20% (percentage by weight).
Wherein, the content of compositions mesostroma adjuvant is 10%-92% (percentage by weight).
The purposes of aforementioned pharmaceutical compositions in periodontitis treatment.
Detailed description of the invention
For the ease of understanding, below will be described in detail the present invention by specific embodiment.It is important to note that these descriptions are only exemplary descriptions, do not form limitation of the scope of the invention.
Embodiment 1
By the iodine 1.3g of recipe quantity, polyvinylpyrrolidone 12.1g, PLGA 50/5021.6g, PLGA 60/4011.3g, be dissolved in qs glycerin formal respectively, mix homogeneously, obtains pharmaceutical composition.
Embodiment 2
By the iodine 2.1g of recipe quantity, polyvinylpyrrolidone 5.1g, PLGA 60/4023.8g PLGA 75/259.8g, be dissolved in appropriate ethyl lactate respectively, mix homogeneously, obtains pharmaceutical composition.
Embodiment 3
By the iodine 11.6g of recipe quantity, poly-meso-lactide 43.1g, polyvinylpyrrolidone 6.4g, be dissolved in appropriate METHYLPYRROLIDONE respectively, mix homogeneously, obtains pharmaceutical composition.
Embodiment 4
By the iodine 4.9g of recipe quantity, polyvinylpyrrolidone 12.6g, PLGA 50/5065.3g, PLGA 75/2510.9g, be dissolved in respectively in dimethyl sulfoxide, mix homogeneously, obtains pharmaceutical composition.
Embodiment 5
By the iodine 8.9g of recipe quantity, polyvinylpyrrolidone 5.9g, PLGA 60/4053.6g, be dissolved in respectively in appropriate 2-Pyrrolidone, mix homogeneously, obtains pharmaceutical composition.
Embodiment 6
By chlorhexidine acetate 0.05g, benzalkonium bromide 0.01g, polyvinylpyrrolidone 6.1g, PLGA 60/4035.8g, PLGA 75/258.8g, be dissolved in appropriate METHYLPYRROLIDONE respectively, mix homogeneously, obtains pharmaceutical composition.
This medicine injects periodontal pocket in liquid form, automatically becomes the semisolid or solid matter with slow releasing function, and slow releasing effective dose medicine reaches about 5 days, greatly facilitates patient medication, reduces medical expense.Technique effect of the present invention is verified below by animal pharmacodynamic experiment and human body pharmacodynamic experiment.
(1) animal pharmacodynamic experiment
1. the foundation of Periodontitis Model and grouping: select 38 tooth body dentures complete, the SD rat of and periodontal disease bad without dental caries, random selecting 5 is matched group (N group), and all the other are periodontitis group (P group).After N group 20% urethane anesthetized animal, fixing animal, be slightly separated the labial surface gingiva of Rat Mandibular incisor, artificial formation does not amputate alveolar bone, only peels off the periodontal pocket of dark about 5mm completely from alveolar bone surface, does not do other process, to compare.Routine Test Lab feedstuff and clear water are fed.After P group 20% urethane anesthetized animal, fixing animal, slightly be separated the labial surface gingiva of Rat Mandibular incisor, artificial formation does not amputate alveolar bone, the periodontal pocket of dark about 5mm is only peeled off completely from alveolar bone surface, use sterile suture ligation in neck portion (taking to stitch the way of 2 pins on neck) again, to cause persistence, the mechanical irritation to periodontal tissue.In rat hindlimb quadriceps femoris, inject prednisolone acetate, every 125mgkg-1d-1, injects 7d continuously simultaneously, replaces clear water to feed simultaneously, and loosen tooth every day with conventional feed+10% sucrose solution.
Through the rat of above-mentioned process after experiment starts, the Clinical changes at routine observation rat experiment position is also noted down.After experiment, within the 4th week, often organize each execution 1 rat, draw materials from Test sites, basis of microscopic observation gingiva tissue pathologic condition.
2. divide into groups: at random rat model is divided into 3 groups, often organize 8, every only 16 teeth.Administration group: injection the present embodiment 1 medicine in periodontal pocket; Positive drug control group: injection minocycline hydrochloride situ-gel in periodontal pocket; Negative control group: in periodontal pocket, injection is not containing the bare substrate of iodine.Each group is all carried out normal diet above, does not inject prednisolone acetate.
3. administration: time baseline (0d), checks animal oral cavity, is loaded in special syringe by the present embodiment 1 medicine in advance.After ether light anesthesia animal, fixing animal, exposes incisor and gingiva position thereof, and use periodontal probe to be removed by gum edge pyorrhea, be then inserted at the bottom of periodontal pocket by the syringe needle of the syringe that normal saline is housed, slow saline injection, flushes out periodontal pocket by pyorrhea.Suck the normal saline in periodontal pocket with filter paper or cotton balls after, inject the present embodiment 1 medicine, until the present embodiment 1 medicine slightly overflows from periodontal pocket.Per-Hop behavior 1 time, continuous 4 weeks.
4. inspection target: respectively at before administration and after administration 1 day, 4 days, 7 days, 2 weeks, 3 weeks, 4 weeks, detect the gingival index of each group of rat, depth of pocket and spy and examine bleeding.
5. statistical procedures
Compare employing variance analysis between group, compare between two and adopt SNK-q inspection.With P < 0.05 for difference has statistical significance.
6. result
As shown in Table 1, drug containing component and positive controls indices (hemorrhage, gingival index, depth of pocket are examined in spy) all have statistical significance with difference during baseline in 1 day upon administration, the present embodiment 1 medicine prepared by explanation and positive drug just make every clinical indices of periodontitis there occurs obvious change for 1 day in administration afterwards, along with the increase of giving number of times, the indices of two groups all constantly declines, and the present embodiment 1 medicine prepared by explanation has therapeutical effect to periodontitis.All there is not obvious change in every periodontal disease index of negative control group, indices and baseline phase, than no significant difference, illustrate that the treatment of bare substrate to periodontitis does not act in experimental period.
Compare between two between many groups that at the end of experiment, (4th week) has carried out the sick index of rat periodontal ligament, result shows, positive controls and the present embodiment 1 medicine all have good therapeutical effect to periodontitis, the two no difference of science of statistics; Negative control group is without therapeutical effect.
Table 1 is respectively organized before treatment and the rear different time periodontal disease Indexes Comparison for the treatment of
(2) human body pharmacodynamics test
1 data and method
Severe chronic periodontitis patient 150 example in 1.1 physical data, wherein male 96 example, women 54 example, 31 ~ 66 years old age, 43.2 years old mean age; Include condition in: 1. healthy, unsystematic disease.2. without pregnant or non-nursing women.3. without tetracycline allergies.4. antibiotic and NSAID (non-steroidal anti-inflammatory drug) is not taken in 2 months.5. do not carry out periodontal disease therapeutic at least 1 week, in oral cavity, retain tooth > 20.6. the Periodontal Probing Depth (PD) of every patient at least 4 teeth reaches 5mm, and there have spy to examine to be hemorrhage.All patients are divided into 3 groups at random, administration group (injecting the present embodiment 2 medicine in periodontal pocket), positive controls (injecting pike change in periodontal pocket), negative control group (giving iodine glycerol to smear), each 50 routine patients, three groups of patients equal no significant difference in sex, age, the course of disease and Clinical typing etc., and no significant difference (P > 0.05), three groups have comparability.
1.2 method three groups patients all give that gingiva is clean, lower gum is scraped treatments such as controlling, and kept root planing, apply 3% hydrogen peroxide and 0.9% normal saline fully rinses periodontal pocket.The present embodiment 2 medicine is filled in the syringe of oral cavity by administration group on this basis, and is put into bottom periodontal pocket by syringe tip and inject gently, until medicine overflows in bag mouth; Pike change ointment (Minocycline ointment) injects in periodontal pocket with method by positive controls, and iodine glycerol injects in periodontal pocket with method by negative control group.Three groups of patients inject all weekly once, judge after treating 4 weeks to curative effect, and advise patient must not drink water, take food and gargle in 2h after medication.
Before 1.3 observation index treatments and treatment respectively the gingival index (GI) of patient, depth of pocket (PD) are carried out mensuration and are compared after 4 weeks.
1.4 curative effect determinate standards are effective: clinical symptoms disappears completely or substantially, and more than GI drop by half, PD minimizing >=2mm; Effective: clinical symptoms is obviously improved, PD reduces by 1 ~ 2mm; Invalid: clinical symptoms is without improvement or even increase the weight of.
1.5 this data of statistical method the data obtaineds all adopt SPSS16.0 to carry out statistical analysis, and measurement data adopts t inspection to analyze, enumeration data application chi-square criterion; P < 0.05 has statistical significance for difference.
2 results
2.1 clinical indices relatively compare GI and the PD index before three groups of patient treatments and after treatment, treatment first three groups index no significant difference, GI and the PD index of the rear administration group for the treatment of and positive controls is significantly less than negative control group and difference has significant statistical significance (P < 0.05), after treatment, GI and the PD index of administration group and positive controls is in the same size, no difference of science of statistics.Refer to table 2.
Before and after table 2 three groups of patient treatments, clinical indices change is compared
The total effective rate of 2.2 comparitive study administration groups and positive controls is 95%, is obviously greater than the total effective rate 70% of negative control group, and difference has significant statistical significance (P < 0.05).The results are shown in Table 3.
Table 3 three groups of patients's comparitive study (n)
| Group | n | Effective | Effectively | Invalid | Total effective rate (%) |
| Administration group | 50 | 36 | 11 | 3 | 94.0 |
| Positive controls | 50 | 37 | 10 | 3 | 94.0 |
| Negative control group | 50 | 24 | 11 | 15 | 70 |
To those skilled in the art, obviously the invention is not restricted to the details of above-mentioned one exemplary embodiment, and when not deviating from spirit of the present invention or basic feature, the present invention can be realized in other specific forms.Therefore, no matter from which point, all should embodiment be regarded as exemplary, and be nonrestrictive, scope of the present invention is limited by claims instead of above-mentioned explanation, and all changes be therefore intended in the implication of the equivalency by dropping on claim and scope are included in the present invention.
Claims (8)
1. treat the pharmaceutical composition of periodontitis for one kind, by principal agent, substrate adjuvant, solvent composition, it is characterized in that: described principal agent is iodine, in iodoform, hibitane, hibitane iodine, benzalkonium bromide, benzalkonium chloride, povidone iodine, triclosan, ethacridine, nitrofural, oradol, myristylpicolinum bromide, silver nitrate, nanometer silver any one or there is two or more combination synergistic.
2. treat the preparation method of the pharmaceutical composition of periodontitis for one kind, comprise the following steps: principal agent, substrate adjuvant are dissolved in solvent respectively, mix homogeneously, obtain, it is characterized in that: described principal agent is iodine, in iodoform, hibitane, hibitane iodine, benzalkonium bromide, benzalkonium chloride, povidone iodine, triclosan, ethacridine, nitrofural, oradol, myristylpicolinum bromide, silver nitrate, nanometer silver any one or there is two or more combination synergistic.
3. compositions according to claim 1 and 2, is characterized in that: described substrate adjuvant is two or more the combination in following adjuvant: poly-levorotatory lactide, poly-meso-lactide, PLGA 90/10, PLGA 75/25, PLGA 60/40, PLGA 50/50, end carboxyl polylactic acid, end carboxyl PLGA, D-lactic acid/co-glycolic acid, D-lactic acid/racemic lactic acid copolymer, polyethylene glycol modified polylactide, polyethylene glycol modified polylactide-co-glycolic acid, poly glycol monomethyl ether polydactyl acid, poly glycol monomethyl ether modification PLGA, lactide coglycolide--caprolactone copolymer, lactide--caprolactone copolymer, lactide coglycolide-trimethylene carbonate PLGTmc, polyvinylpyrrolidone, Polyethylene Glycol, the husky nurse of POLO, aminoacid, potassium iodide.
4. compositions according to claim 3, it is characterized in that: described substrate adjuvant is: PLGA 50/50, PLGA 75/25 and polyvinylpyrrolidone, three's mixed weight is than being 20-80:6-35:0.6-13.
5. compositions according to claim 1 and 2, is characterized in that: described solvent is METHYLPYRROLIDONE, ethyl acetate, triacetyl glycerine, 2-Pyrrolidone, ethyl lactate, dimethyl sulfoxide, glycerol formal.
6. compositions according to claim 1 and 2, is characterized in that: described drug content is 0.5%-20% (percentage by weight).
7. compositions according to claim 1 and 2, is characterized in that: the content of described substrate adjuvant is 10-92% (percentage by weight).
8. the arbitrary described purposes of pharmaceutical composition in periodontitis treatment of claim 1-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410843035.1A CN104586888A (en) | 2014-12-30 | 2014-12-30 | Pharmaceutical composition for treating periodontitis and method for preparing pharmaceutical composition for treating periodontitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410843035.1A CN104586888A (en) | 2014-12-30 | 2014-12-30 | Pharmaceutical composition for treating periodontitis and method for preparing pharmaceutical composition for treating periodontitis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104586888A true CN104586888A (en) | 2015-05-06 |
Family
ID=53113160
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410843035.1A Pending CN104586888A (en) | 2014-12-30 | 2014-12-30 | Pharmaceutical composition for treating periodontitis and method for preparing pharmaceutical composition for treating periodontitis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104586888A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2600036C1 (en) * | 2015-07-21 | 2016-10-20 | Автономная некоммерческая организация высшего профессионального образования "Белгородский университет кооперации, экономики и права" | Method of producing biocide agent in the form of furacilin solution |
| CN107898521A (en) * | 2017-12-22 | 2018-04-13 | 大连三生科技发展有限公司 | A kind of cleaning method of planting body |
| CN107920510A (en) * | 2015-08-24 | 2018-04-17 | 史密夫和内修有限公司 | Synergistic antimicrobial activity of the combination of middle polarity oil and antiseptic in bacterial biof iotalm |
| CN108030788A (en) * | 2017-12-15 | 2018-05-15 | 保髓特（天津）生物科技有限公司 | A kind of pulpitis treatment paste and its application |
| WO2018202687A1 (en) * | 2017-05-02 | 2018-11-08 | Pierre Fabre Medicament | Antiseptic composition combining chlorhexidine and iodine |
| CN110151945A (en) * | 2019-04-26 | 2019-08-23 | 西安交通大学 | Anti-periodontitis composition and its application in the preparation of medicines for treating periodontitis |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101584889A (en) * | 2009-07-10 | 2009-11-25 | 山东大学威海分校 | External in-situ forming matrix used for treating periodontal diseases |
| WO2011012855A2 (en) * | 2009-07-28 | 2011-02-03 | Raymond Stanley Steggles | Antibacterial compositions |
| CN102240277A (en) * | 2011-06-02 | 2011-11-16 | 深圳南粤药业有限公司 | Pharmaceutical composition for treating periodontitis, and preparation method and application thereof |
| CN103006444A (en) * | 2011-09-28 | 2013-04-03 | 韩冰 | Use of gel material in therapeutic process of dental disease |
| CN103784394A (en) * | 2014-02-11 | 2014-05-14 | 凌春生 | Intelligent temperature-sensitive sustained-release gel and preparation method thereof |
-
2014
- 2014-12-30 CN CN201410843035.1A patent/CN104586888A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101584889A (en) * | 2009-07-10 | 2009-11-25 | 山东大学威海分校 | External in-situ forming matrix used for treating periodontal diseases |
| WO2011012855A2 (en) * | 2009-07-28 | 2011-02-03 | Raymond Stanley Steggles | Antibacterial compositions |
| CN102240277A (en) * | 2011-06-02 | 2011-11-16 | 深圳南粤药业有限公司 | Pharmaceutical composition for treating periodontitis, and preparation method and application thereof |
| CN103006444A (en) * | 2011-09-28 | 2013-04-03 | 韩冰 | Use of gel material in therapeutic process of dental disease |
| CN103784394A (en) * | 2014-02-11 | 2014-05-14 | 凌春生 | Intelligent temperature-sensitive sustained-release gel and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| NING LIU,ET AL: "Preparation and in vitro drug release studies of iodine thermosensitive in situ ge", 《CANCER CELL RESEARCH》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2600036C1 (en) * | 2015-07-21 | 2016-10-20 | Автономная некоммерческая организация высшего профессионального образования "Белгородский университет кооперации, экономики и права" | Method of producing biocide agent in the form of furacilin solution |
| CN107920510A (en) * | 2015-08-24 | 2018-04-17 | 史密夫和内修有限公司 | Synergistic antimicrobial activity of the combination of middle polarity oil and antiseptic in bacterial biof iotalm |
| US11197476B2 (en) | 2015-08-24 | 2021-12-14 | Smith & Nephew, Inc. | Synergistic antibacterial activity of medium polarity oils in combination with antibacterial agents on bacterial biofilms |
| US11641856B2 (en) | 2015-08-24 | 2023-05-09 | Smith & Nephew, Inc. | Synergistic antibacterial activity of medium polarity oils in combination with antibacterial agents on bacterial biofilms |
| WO2018202687A1 (en) * | 2017-05-02 | 2018-11-08 | Pierre Fabre Medicament | Antiseptic composition combining chlorhexidine and iodine |
| FR3065879A1 (en) * | 2017-05-02 | 2018-11-09 | Pierre Fabre Medicament | ANTISEPTIC COMPOSITION OF A CHLORHEXIDINE AND IODINE ASSOCIATION |
| CN108030788A (en) * | 2017-12-15 | 2018-05-15 | 保髓特（天津）生物科技有限公司 | A kind of pulpitis treatment paste and its application |
| CN107898521A (en) * | 2017-12-22 | 2018-04-13 | 大连三生科技发展有限公司 | A kind of cleaning method of planting body |
| CN110151945A (en) * | 2019-04-26 | 2019-08-23 | 西安交通大学 | Anti-periodontitis composition and its application in the preparation of medicines for treating periodontitis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104586888A (en) | Pharmaceutical composition for treating periodontitis and method for preparing pharmaceutical composition for treating periodontitis | |
| Hong | Considerations in the pediatric population with cancer | |
| NO331317B1 (en) | Use of moxifloxacin for the preparation of a drug for topical and / or topical treatment of wounds caused by infections | |
| WO1995009601A1 (en) | Use of azithromycin for the treatment of adult periodontitis and topical compositions for this use | |
| DE202016102375U1 (en) | Dental agent based on hyaluronan and octenidine dihydrochloride | |
| Amaliya et al. | The effectiveness of 0.2% chlorhexidine gel on early wound healing after tooth extraction: a randomized controlled trial | |
| Ahmed et al. | Ozone applications in dentistry: an overview. | |
| CN1238054C (en) | Biotechnological formulation for suppressing and killing helicobacter pylori, its preparation and use | |
| CN106309483A (en) | Inflammation-diminishing paste for dental pulp, and preparation method of inflammation-diminishing paste | |
| Tirali et al. | Antimicrobial efficacy of octenidine hydrochloride, MTAD and chlorhexidine gluconate mixed with calcium hydroxide | |
| Steinberg et al. | The effect of parabens in a mouthwash and incorporated into a sustained release varnish on salivary bacteria | |
| Kumari et al. | Comparative evaluation of intracanal cryotherapy and curcumin as a final irrigant in reducing post endodontic pain in primary teeth | |
| Hrynovets et al. | Research design of the release of Amizon, Decametoxine, and Chlorhexidine from the composition of dental medicinal films | |
| CN108299372B (en) | Medicine for preventing and treating gingivitis and preparation method thereof | |
| ES2308975T3 (en) | ENDODONTIC FIBERS AND THEIR PROCEDURES OF USE. | |
| De Freitas et al. | Aggressive periodontitis associated with Papillon‐Lefèvre syndrome: Report of a 14‐year follow‐up | |
| Giboin et al. | Safety and efficacy of cefovecin (Convenia®) as an adjunctive treatment of periodontal disease in dogs | |
| RU2580615C1 (en) | Method of treating periodontitis | |
| Khlyebas | A comparative analysis of the clinical efficiency of the treatment of chronic granulomatous periodontitis using different protocols of drug treatment of the root canals | |
| Dixit et al. | Comparative evaluation of antimicrobial efficacy of various intracanal medicament in young permanent teeth: An in vivo study | |
| US20070020200A1 (en) | Therapeutic compositions and methods of use thereof | |
| Tymofieiev et al. | Prevention of Inflammatory Complications in Fractures of Alveolar Processes of the Jaw | |
| Badiea | Efficacy of Intra-Pocket Application of Two Antimicrobial Agents as an Adjunct to Mechanotherapy of Chronic Periodontitis (a Comparative Study) | |
| Masruri et al. | Case Report: Early Detection of Leukemia at Oral Mucosa on an Elderly Woman Patient | |
| CN103623414A (en) | Local medicine delivery sustained-release preparation for treating periodontosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150506 |
|
| WD01 | Invention patent application deemed withdrawn after publication |