CN101606902A - Contraceptive vagina gel with function of killing microorganism - Google Patents
Contraceptive vagina gel with function of killing microorganism Download PDFInfo
- Publication number
- CN101606902A CN101606902A CNA2008100535627A CN200810053562A CN101606902A CN 101606902 A CN101606902 A CN 101606902A CN A2008100535627 A CNA2008100535627 A CN A2008100535627A CN 200810053562 A CN200810053562 A CN 200810053562A CN 101606902 A CN101606902 A CN 101606902A
- Authority
- CN
- China
- Prior art keywords
- gel
- contraceptive
- stir
- antibacterial
- substrate
- 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
- 210000001215 vagina Anatomy 0.000 title claims abstract description 28
- 230000002254 contraceptive effect Effects 0.000 title claims abstract description 26
- 239000003433 contraceptive agent Substances 0.000 title claims abstract description 24
- 244000005700 microbiome Species 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 238000003756 stirring Methods 0.000 claims abstract description 28
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 23
- 239000000758 substrate Substances 0.000 claims abstract description 22
- 239000008213 purified water Substances 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 20
- -1 antibacterial Substances 0.000 claims abstract description 18
- 239000000080 wetting agent Substances 0.000 claims abstract description 16
- 239000000934 spermatocidal agent Substances 0.000 claims abstract description 15
- 230000002421 anti-septic effect Effects 0.000 claims abstract description 14
- 239000012456 homogeneous solution Substances 0.000 claims abstract description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 57
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 54
- JYCQQPHGFMYQCF-UHFFFAOYSA-N 4-tert-Octylphenol monoethoxylate Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCO)C=C1 JYCQQPHGFMYQCF-UHFFFAOYSA-N 0.000 claims description 20
- 229920001607 Policresulen Polymers 0.000 claims description 20
- 229950004053 octoxinol Drugs 0.000 claims description 20
- ACZKMKGNTMOPBD-UHFFFAOYSA-N policresulen Chemical compound CC1=CC(O)=C(S(O)(=O)=O)C=C1CC1=CC(S(O)(=O)=O)=C(O)C(CC=2C(=CC(O)=C(C=2)S(O)(=O)=O)C)=C1C ACZKMKGNTMOPBD-UHFFFAOYSA-N 0.000 claims description 20
- 229960002954 policresulen Drugs 0.000 claims description 20
- 235000011187 glycerol Nutrition 0.000 claims description 18
- 239000002994 raw material Substances 0.000 claims description 10
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 8
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 6
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical group [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 6
- 239000004302 potassium sorbate Substances 0.000 claims description 6
- 235000010241 potassium sorbate Nutrition 0.000 claims description 6
- 229940069338 potassium sorbate Drugs 0.000 claims description 6
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 6
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 6
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 229960005053 tinidazole Drugs 0.000 claims description 4
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 claims description 3
- LKAPTZKZHMOIRE-KVTDHHQDSA-N (2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolane-2-carbaldehyde Chemical compound OC[C@H]1O[C@H](C=O)[C@@H](O)[C@@H]1O LKAPTZKZHMOIRE-KVTDHHQDSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229960004125 ketoconazole Drugs 0.000 claims description 3
- 229960000282 metronidazole Drugs 0.000 claims description 3
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 3
- 239000004299 sodium benzoate Substances 0.000 claims description 3
- 235000010234 sodium benzoate Nutrition 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 229960004365 benzoic acid Drugs 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 229960003885 sodium benzoate Drugs 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 27
- 230000000845 anti-microbial effect Effects 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 210000004877 mucosa Anatomy 0.000 abstract description 5
- 231100000419 toxicity Toxicity 0.000 abstract description 4
- 230000001988 toxicity Effects 0.000 abstract description 4
- 238000001228 spectrum Methods 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 98
- 238000012360 testing method Methods 0.000 description 35
- 239000001963 growth medium Substances 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- 241000283973 Oryctolagus cuniculus Species 0.000 description 17
- 208000019802 Sexually transmitted disease Diseases 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 241000894006 Bacteria Species 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 241000186660 Lactobacillus Species 0.000 description 12
- 229940039696 lactobacillus Drugs 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 238000005303 weighing Methods 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 239000013641 positive control Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 241000233866 Fungi Species 0.000 description 10
- 208000030507 AIDS Diseases 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000001954 sterilising effect Effects 0.000 description 8
- 238000004659 sterilization and disinfection Methods 0.000 description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 7
- 229920001817 Agar Polymers 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229920002125 Sokalan® Polymers 0.000 description 6
- 206010047786 Vulvovaginal discomfort Diseases 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000008272 agar Substances 0.000 description 6
- 230000003509 anti-fertility effect Effects 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 229960001631 carbomer Drugs 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 235000015097 nutrients Nutrition 0.000 description 6
- 210000000582 semen Anatomy 0.000 description 6
- 241000222122 Candida albicans Species 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 241000191967 Staphylococcus aureus Species 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 229940087419 nonoxynol-9 Drugs 0.000 description 5
- 229920004918 nonoxynol-9 Polymers 0.000 description 5
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 description 5
- 229940095731 candida albicans Drugs 0.000 description 4
- 239000012531 culture fluid Substances 0.000 description 4
- 230000009849 deactivation Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000006916 nutrient agar Substances 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 241000143437 Aciculosporium take Species 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 230000027326 copulation Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 210000003754 fetus Anatomy 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 230000016087 ovulation Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- OJIYIVCMRYCWSE-UHFFFAOYSA-M Domiphen bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 OJIYIVCMRYCWSE-UHFFFAOYSA-M 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010018612 Gonorrhoea Diseases 0.000 description 2
- 240000001046 Lactobacillus acidophilus Species 0.000 description 2
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000003851 azoles Chemical class 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 229940082484 carbomer-934 Drugs 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229960001859 domiphen bromide Drugs 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 230000012173 estrus Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 208000001786 gonorrhea Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 1
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 1
- XWBADQOPXPRKBX-FMIVXFBMSA-N 1-n,1-n-diethyl-4-n-[6-methoxy-2-[(e)-2-(4-nitrophenyl)ethenyl]quinolin-4-yl]pentane-1,4-diamine Chemical compound N=1C2=CC=C(OC)C=C2C(NC(C)CCCN(CC)CC)=CC=1\C=C\C1=CC=C([N+]([O-])=O)C=C1 XWBADQOPXPRKBX-FMIVXFBMSA-N 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- MBRHNTMUYWQHMR-UHFFFAOYSA-N 2-aminoethanol;6-cyclohexyl-1-hydroxy-4-methylpyridin-2-one Chemical compound NCCO.ON1C(=O)C=C(C)C=C1C1CCCCC1 MBRHNTMUYWQHMR-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- UYIFTLBWAOGQBI-BZDYCCQFSA-N Benzhormovarine Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3OC(=O)C1=CC=CC=C1 UYIFTLBWAOGQBI-BZDYCCQFSA-N 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000543821 Oestrus Species 0.000 description 1
- 229920000153 Povidone-iodine Polymers 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000007313 Reproductive Tract Infections Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047799 Vulvovaginitis trichomonal Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003716 antitrichomonal agent Substances 0.000 description 1
- 238000004500 asepsis Methods 0.000 description 1
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 239000003364 biologic glue Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229940097572 chloromycetin Drugs 0.000 description 1
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 description 1
- 229960004022 clotrimazole Drugs 0.000 description 1
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical class [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229950002007 estradiol benzoate Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000002304 glucoses Chemical class 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 description 1
- 229940025878 hesperidin Drugs 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 1
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 235000007079 manganese sulphate Nutrition 0.000 description 1
- BZDIAFGKSAYYFC-UHFFFAOYSA-N manganese;hydrate Chemical compound O.[Mn] BZDIAFGKSAYYFC-UHFFFAOYSA-N 0.000 description 1
- 238000011177 media preparation Methods 0.000 description 1
- 230000029052 metamorphosis Effects 0.000 description 1
- 229960002509 miconazole Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229960001621 povidone-iodine Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 108010009004 proteose-peptone Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical class [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
- 235000011046 triammonium citrate Nutrition 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229940044950 vaginal gel Drugs 0.000 description 1
- 239000000029 vaginal gel Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003253 viricidal effect Effects 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of contraceptive vagina gel, belong to contraceptive with function of killing microorganism.Gel of the present invention is made up of spermicide, antibacterial, substrate, wetting agent, antiseptic and water, and make gel: substrate is added in the wetting agent by following steps, stir while adding and make it to be uniformly dispersed, add spermicide again, stir; Get antibacterial, antiseptic and add in the purified water of preparation amount and stir into homogeneous solution, more than two kinds of solution mix, stir the back deaeration and promptly make.The present invention is a compound preparation, except that contraceptive efficacy is arranged, also has the wide spectrum anti-microbial effect, select for use hydroxypropyl emthylcellulose to do gel, make medicine and vaginal mucosa that excellent biological compatibility be arranged, it is strong and adhesion time is long, difficult loss to have an adhesion, advantages such as the time of remaining valid is long, and toxicity is low, zest is little.
Description
Technical field
The present invention relates to contraceptive and preparation method, specifically is a kind of contraceptive vagina gel with function of killing microorganism.
Background technology
Acquired immune deficiency syndrome (AIDS) has entered the quick rise period at the popular of China, and is nearly 1,000,000 according to China's Ministry of Public Health 2002 annual reports whole nations patients infected hiv, and the number of the infected of China's acquired immune deficiency syndrome (AIDS), sexually transmitted disease (STD) is just with annual 30% speed increment.In the women of AIDS viral infection, the overwhelming majority is the women of child-bearing age, and the trafficability characteristic behavior contagion also can cause mother-to-baby transmission after they are infected.In order to reduce propagation unwillingly pregnant and sexually transmitted disease (STD) such as preventing AIDS, as a kind of strategy that prevents AIDS, international organizations such as World Health Organization (WHO) and UNAIDS will first develop project by the microbicidel contraception preparation conduct that the women initiatively uses.In order to safeguard women's healthy reproduction; the legitimate rights and interests that shield women; study and a kind ofly initiatively to use and control by the women; the external microbicidel contraception preparation that can prevent AIDS, spread of sexually transmitted diseases can reduce unwillingly gestation again is very important, this to reduce gestation unwillingly and prevent AIDS, the propagation of sexually transmitted disease (STD) has double meaning.
The research in this field now is very active, and the precious sterilization of the microbicidel contraceptive-health and happiness cream of domestic the Changjiang river Bioceuticals Inc. development is a kind of compound gel, obtains the font size product that disappears of Ministry of Public Health.Also there is the people it to be claimed " liquid condom ".
U.S. Rush-Presbyterian-St. Luke's Medical Center in Chinese patents number is the patent of 01809090.7 " catching compositions and method with inactivating pathogenic microbes and sperm ", the method of antimicrobial and composition for contraception is provided, can have prevented and/or reduce the sexually transmitted disease (STD) that the trafficability characteristic activity is propagated.With prevent and/or reduce conceivedly dangerous that 1. compositions contains that substrate forms agent, 2. biological adhesive, 3. buffer agent, 4. optional wetting agent, 5. optional antiseptic and 6. water; Wherein compositions is suitable for being coated in intravaginal, with after seminal fluid contacts, forms semisolid matrix (thereby catching microorganism and the sperm that ejaculation discharges); Wherein compositions causes cervical mucus sclerosis (thereby reducing probability that sperm enters), and forms bioadhesive layer (thereby prevent or reduce the danger that the microorganism that causes sexually transmitted disease (STD) contacts with vagina surface) at vagina surface; Compositions is kept acid vagina less than pH5 in the presence of the seminal fluid that male ejaculation discharges; And wherein compositions can obviously not damaged intravaginal normal microbial balance.Antimicrobial and composition for contraception can also contain other antimicrobial and/or contraceptive (as the hesperidin of nonoxynolum, Octoxinol, benzalkonium chloride, phosphorylation, Sulfonated hesperidin, polystyrolsulfon acid ester, the benzenesulfonic acid copolyoxymethylenes of replacement, H
2SO
4The mandelic acid of modification, povidone iodine, itraconazole, ketoconazole, metronidazole, clotrimazole, fluconazol, Te Lakang azoles, miconazole, tinidazole, Yi Kang azoles, chloromycetin, nystatin, ciclopiroxolamin etc.).Though the numerous prescriptions of this patent one-tenth capable of being combined are not that each prescription can both be prepared adaptable compositions.
Summary of the invention
The present invention is big to vaginal irritation in order to solve the prior art Chinese medicine, formula material is many, preparation method complicated problems and provide a kind of and can reduce unwillingly gestation by the autonomous use of women and can reduce HIV and other sexually transmitted disease (STD) sickness rate, the contraceptive rate height, the prevention reproductive tract infection is effective, technology is simple, and is easy to use, the contraceptive vagina gel with function of killing microorganism little to vaginal irritation.
Contraceptive vagina gel with function of killing microorganism involved in the present invention, its component comprises spermicide, antibacterial, substrate, wetting agent, antiseptic and water, and make gel: substrate is added in the wetting agent by following steps, stir while adding and make it to be uniformly dispersed, add spermicide again, stir; Get antibacterial, antiseptic and add in the purified water of preparation amount and stir into homogeneous solution, more than two kinds of solution mix, stir the back deaeration and promptly make gel.
The proportioning of this gel raw material weight percentage ratio is as follows: spermicide 0.1～5, antibacterial 0.1～3, substrate 1～10, wetting agent 1～50, antiseptic 0.01～0.5, surplus are purified water.
The proportioning of this gel raw material weight percentage ratio is as follows: spermicide 2, antibacterial 1.8, substrate 5, wetting agent 20, antiseptic 0.15, surplus are purified water.
Above-mentioned spermicide is selected from a kind of in Nonoxynol-9 and the Octoxinol, and antibacterial is selected from policresulen, ketoconazole, metronidazole and the tinidazole any one or two kinds.Substrate is selected from sodium carboxymethyl cellulose, sodium alginate, poly-chitose, polyvinylpyrrolidone and the hydroxypropyl emthylcellulose any one or two kinds, and wetting agent is selected from propylene glycol, glycerol and the Polyethylene Glycol any one or two kinds of.Antiseptic is selected from one or both in sorbic acid, potassium sorbate, benzoic acid, sodium benzoate and the parabens.
Gel of the present invention mainly comprises substrate, antibacterial, spermicide, wetting agent and antiseptic.
The spermicide Octoxinol has same spermicide effect with the sub-agent nonoxynolum of using always of external use sperm killing, but little to the stimulation of vagina, makes user more acceptant, so antibacterial of the present invention adopts Octoxinol.
Policresulen is a kind of strong acid; the surface has negative charge; its biggest advantage is that selectively acting is in the time of pathological tissues; still keep normal acid vagina environment; be unfavorable for various pathogenic microorganism growth and breedings; and help the breeding of growing of lactobacillus, and protect normal vagina squamous epithelial cancer.Policresulen has broad-spectrum antibacterial action, comprises gram positive bacteria, gram-negative bacteria, fungus and some virus, wherein, the vagina Gartner all, anaerobe infusorian and candidiasis to particularly responsive.But vagina lactobacillus flora is unaffected substantially, therefore can keep the balance of the normal microorganism of vagina.
Can be many as the material of gel-type vehicle, as carbomer, sodium carboxymethyl cellulose (CMC-Na), poly-chitose, polyvinylpyrrolidone, hydroxypropyl emthylcelluloses etc. are several macromolecular materials that are commonly used for gel-type vehicle, but be not that every kind of material all is fit to do gel-type vehicle of the present invention, be suitable for substrate of the present invention and should be able in lower pH value scope, keep the stable of performance, make medicine and vaginal mucosa that excellent biological compatibility be arranged, it is long also should to have the time of sticking simultaneously, adhesion strength is strong, be difficult for running off, the time of remaining valid is long, toxicity is low, bland characteristics.The present invention selects carbomer, sodium carboxymethyl cellulose, three kinds of materials of hydroxypropyl emthylcellulose to screen by following experiment, finally selects hydroxypropyl emthylcellulose (HPMC) as gel-type vehicle.
1. carbomer matrix gel agent
Prescription policresulen 1.8g
Octoxinol 2.0g
Carbomer 934 P 2.0g
Glycerol 10g
Propylene glycol 10g
Triethanolamine is an amount of
Purified water is an amount of
Gross weight 100g
Preparation process: following each raw material takes by weighing by formula ratio.
A. take by weighing glycerol, propylene glycol is poured beaker into, add carbomer and stir; Add purified water 60ml, add Octoxinol again, continue to stir, drip triethanolamine and make pH ≈ 4.5, be transparent, colourless gel.
B. add policresulen in above-mentioned gel, the limit edged stirs, and it is thin that gel becomes, and is rufous liquid, can't be shaped.Record pH value with the pH reagent paper and be about 2.
Conclusion: carbomer is not suitable for doing the gel substrate that contains above-mentioned principal agent composition.
2. sodium carboxymethyl cellulose (CMC-Na) matrix gel agent
Prescription policresulen 1.8g
Octoxinol 2.0g
Glycerol 10g
Propylene glycol 10g
CMC-Na 2.5g
Purified water is an amount of
Gross weight 100g
Preparation process: following each raw material takes by weighing by formula ratio.
A. take by weighing glycerol, propylene glycol is poured beaker into, adds CMC-Na and stirs, and adds Octoxinol, continues to stir, and makes mixture 1.
B. claim policresulen in beaker, add the purified water of preparation amount, stir, solution is rufous, makes solution 2.
C. solution 2 is poured in the mixture 1, stirred while adding, the solution thickness that becomes gradually is until being uniform state.
3. the blank gel of CMC-Na substrate that does not contain medicine
Prescription glycerol 10g
Propylene glycol 10g
CMC-Na 2.5g
Purified water is an amount of
Gross weight 100g
Preparation process: following each raw material takes by weighing by formula ratio.
Take by weighing glycerol, propylene glycol is poured beaker into, adds CMC-Na and stirs, adding the purified water ad pond om is 100g, stirs while adding, and is the semi-solid gel state until liquid, colourless opaque.
Viscosity measurement
Sample thief 100ml puts into beaker, measures with NDJ-85 type Digital Viscometer, and the blank sample average viscosity is 30.0Pa.S.
Two kinds of CMC-Na matrix gel agent viscosity ratios
Conclusion: can make with CMC-Na behind the adding medicine is the gel viscosity degradation of substrate.
4. hydroxypropyl emthylcellulose (HPMC) matrix gel agent
Prescription policresulen 1.8g
Octoxinol 2.0g
Glycerol 10g
Propylene glycol 10g
HPMC 3.0g
Purified water is an amount of
Gross weight 100g
Preparation process: following each raw material takes by weighing by formula ratio.
A. take by weighing glycerol, propylene glycol is poured beaker into, adds HPMC and stirs, and adds Octoxinol, continues to stir, and makes mixture 1.
B. take by weighing policresulen in beaker, add the purified water of preparation amount, stir, solution is rufous, makes solution 2.
C. solution 2 is poured in the mixture 1, stirred while pour into, solution becomes sticky thick gradually, and until being semi-solid state, transparent red is brown.
5. the blank gel of HPMC substrate that does not contain medicine
Prescription glycerol 10g
Propylene glycol 10g
HPMC 3.0g
Purified water adds ad pond om 100g
Preparation process: the preparation method that does not ditto contain the blank gel of CMC-Na substrate of medicine.
Viscosity measurement: method is the same.
Ratio of viscosities
Conclusion: HPMC is suitable for doing the gel-type vehicle of above-mentioned main component.
In the test viscosity and outward appearance are compared:
1.2, the gel that does not contain principal agent made as gel-type vehicle with 2.5% sodium carboxymethyl cellulose (CMC-Na) in No. 3 prescriptions compares with the gel that contains the principal agent composition, dynamic viscosity descends, and reduces to 15～20Pa.S by 30～40Pa.S.The gel brownish red of making is opaque.
2.1 the gel of making as gel-type vehicle with 2% carbomer 934 P in number prescription, behind the adding principal agent, dynamic viscosity sharply descends, and solution becomes is thin.Because principal agent is acidic materials, carbomer is done gel-type vehicle, and influenced by acid-base value very big, the too high or too low formation that all influences dosage form of pH value.The gel that carbomer forms is very stable in pH 5～11 scopes, the thickness o'clock the most in pH 6～12, when pH＜3 or＞12 the time, viscosity is 1000mPa.S, pH is that 8 o'clock viscosity increases to 50Pa.S.The brownish red of principal agent is thin out in can be made into the pH scope of gel, influences content.
3. hydroxypropyl emthylcellulose is more stable to soda acid, but as exceed pH 2～11 scopes and be subjected to higher temperature simultaneously or deposit the long period, then can make viscosity degradation.With 2.5% to 3.2% hydroxypropyl emthylcellulose (HPMC) is that the gel viscosity made of gel-type vehicle is moderate, the dynamic viscosity 25-30Pa.S vaginal application that suits.The gel brownish red of making, transparent.
The present invention selects for use the macromolecular material hydroxypropyl emthylcellulose to do gel substrate, it dissolves in water and not influenced by pH value, has thickening capabilities, salt discharge, pH stability, water-retaining property, dimensional stability, and anti-widely enzyme, dispersibility and caking property, make medicine and vaginal mucosa that excellent biological compatibility be arranged, it is strong and adhesion time is long to have adhesion, be difficult for running off, the time of remaining valid is long, advantages such as toxicity is low, zest is little, be an effective new vaginal gel substrate, have good potential applicability in clinical practice.
Being suitable for wetting agent of the present invention has polyhydric alcohol such as glycerol, propylene glycol, Polyethylene Glycol, and toxicity is little, nonirritant, and the mixed solvent of a certain proportion of propylene glycol and water can delay the hydrolysis of many medicines, increases stability.To the be absorbed with facilitation of medicine at skin and mucosa, the present invention adopts glycerol, propylene glycol not only can preserve moisture as wetting agent but also can increase the transparency of gel.
Manufacture method of the present invention is simple, because policresulen itself is acid, so there is no need to add acid buffer agent, reuse alkali is transferred the ph value again, has therefore reduced cost, has reduced operation.
Advantage and good effect that the present invention has are
The present invention is a compound preparation, except that contraceptive efficacy is arranged, also has the wide spectrum anti-microbial effect, comprising: virus, antibacterial, mycete and protozoon.This gel can independently be used and controlled by the women, and existing effect of killing smart contraception can reduce HIV and other sexually transmitted disease (STD) sickness rate again, thereby is reducing the healthy reproduction right that the women has unwillingly protected the women aspect gestation and the reduction women HIV infection rate two.Compared with prior art, it is simple that the present invention has a preparation process, use convenient, little to the zest of vagina, the advantage that comfort is strong.
The specific embodiment
The preparation method of embodiment 1 gel of the present invention
Raw material:
Hydroxypropyl emthylcellulose, propylene glycol, glycerol, potassium sorbate are all commercially available.Policresulen: Qihe synthetic Fine Chemical Co., Ltd in Jinan provides lot number: 050802; Octoxinol: Sigma's aldrich (Shanghai) trading company (ICEPL CA 630), lot number: 075K0071; Purified water: self-control.
Prescription
Hydroxypropyl emthylcellulose 3.0g
Propylene glycol 10g
Glycerol 10g
Policresulen 1.8g
Octoxinol 2.0g
Potassium sorbate 0.15g
Purified water is an amount of
Total amount 100g
Preparation method:
Take by weighing propylene glycol, glycerol by formula ratio, behind the mix homogeneously, add hydroxypropyl emthylcellulose while stirring mixed liquor is uniformly dispersed, add Octoxinol again, stir.Stir into homogeneous solution in the purified water with potassium sorbate and policresulen adding preparation amount respectively, solution is poured in the above-mentioned mixed liquor, stir the back deaeration and get final product.The gel of preparation is the translucent semisolid of brownish red.
Below by toxicology, pharmacological every test, further specify the good effect of gel of the present invention.
One. acute toxicity test (LD
50)
1. material
1.1 medicine
Gel of the present invention is pressed embodiment 1 preparation; Provide by the Birth Control Institute, Tianjing City.
1.2 animal
Kunming kind healthy mice, male and female half and half, body weight are between 18g-22g, and institute provides by the Tianjin drug research, and the laboratory animal quality certification is that big mice laboratory animal, production facility meet the barrier grade standard, accurate No. 012.
2. method
Adopt the Bliss method to measure the LD of the contraceptive vagina gel of energy deactivation microorganism
50Conform after animal is bought a week, do trial test with a small amount of mice earlier, survey its complete dead and full sublethal dose.Mice is divided into 5 groups at random by body weight, and 10 every group, male and female half and half.Each dosage group spacing is 0.8, and each is organized dosage and is respectively 66mg/kg, 82mg/kg, 102mg/kg, 128mg/kg and 160mg/kg.Carry out once abdominal cavity injection by 0.1ml/10g.Observe the reaction of mice after the administration immediately, observe a week continuously, write down the weight of animals variation, toxic reaction situation and dead animal every day and distribute.Dead animal in time performs an autopsy on sb, and record pathological changes situation is calculated LD with computer
50Value.Concrete data see Table 1.
The LD of the conception control gel agent of table 1 energy deactivation microorganism
50Experimental data
Can get conclusion by above data: the LD of gel intraperitoneal administration of the present invention
50Be 95.88mg/kg, credible scope is 83.78-109.71mg/kg.When mouse peritoneal drug administration by injection amount is 16.7 times of people's kg body weight, still can tolerate.
Two. to the test of lactobacillus influence
Lactobacillus is the dominant bacteria in the normal flora in the vagina, plays an important role to keeping the intravaginal colony balance.Gel of the present invention is as the vagina preparation that microbicidel and contraceptive efficacy are arranged, and it is very meaningful to observe its influence to the vagina lactobacillus.Therefore be test strain with lactobacillus acidophilus, observe the influence of gel the lactobacillus of cultivation, for the safety of further estimating this gel preparation provides scientific basis,
Materials and methods
1. material
Experimental strain: lactobacillus acidophilus (ATCC4356): purchase in Institute of Microorganism, Academia Sinica strain center;
Sample: gel: press embodiment 1 preparation; The Birth Control Institute, Tianjing City provides
Negative control thing: normal saline;
Positive control: domiphen bromide (bromination N, N-dimethyl-N-(2-benzene oxygen ethyl)-1-dodecane ammonium monohydrate) Qingyang pharmaceutcal corporation, Ltd; Lot number: 031003;
Lactic acid bacteria culture fluid (MRS): by formulated;
Prescription:
Casein peptone 10.0 gram beef leaching things 10.0 grams
Yeast extract 5.0 gram glucoses 20.0 grams
Sodium acetate 5.0 gram triammonium citrates 2.0 grams
Tween 80 1.0 gram dipotassium hydrogen phosphates 2.0 grams
Magnesium sulfate heptahydrate 0.2 gram four water manganese sulfates 0.05 gram
Distilled water 1000ml
Compound method: in conical flask, after stirring, at 121 ℃ of sterilization 15min, pH 6.2～6.4, and is standby with pressure cooker with above-mentioned formula ratio material.
2. equipment
Detest foster culture tank: 2.4 liters of Beijing Orient of bo3-A type are believed Bioisystech Co., Ltd in vain; The Maxwell opacity tube
3. method
3.1. the preparation of sample: precision takes by weighing an amount of gel sample, makes it contain policresulen with normal saline dilution gel and is respectively 4.5,9, and the solution of 18,36 (mg/ml) is sample, and is standby.Precision takes by weighing an amount of domiphen bromide, is mixed with concentration with normal saline and is respectively 4.5,9, and the positive contrast of the solution of 18,36 (mg/ml) is standby.The negative contrast of normal saline.
3.2. the cultivation of bacterium liquid: with 121 ℃ of MRS culture fluid, 15mi n sterilization.Lactobacillus is inoculated in the MRS culture fluid, and 37 ℃ of anaerobism are cultivated 48h, use the Maxwell opacity tube and make standard, determine that the lactobacillus concentration of cultivating is 1.5-3.0 * 10
8The time standby
3.3. experimental technique: adopt the filter paper agar diffusion method to test.With MRS culture fluid and 3% agar solution by after 1: 1 mixed, 121 ℃ of 20min sterilizations.Finish following operation in superclean bench: adding the 20ml mixed liquor in each culture dish is the bottom culture medium, and after waiting to solidify, essence is got the lactobacillus of the fresh propagation of 0.3ml, fills with in the culture dish of completing bottom.Get aseptic and exsiccant circular filter paper sheet (diameter is 6mm), go up the solution 10u l that drips a kind of concentration for every, with tweezers filter paper is put into culture dish gently then, the class of operation of reference substance is same as sample, each culture dish is put 3 sample filter papers, 1 positive control sheet and 1 negative control sheet, totally 5.After subsides are put well, gently press print, make it be close to the plate surface, build plate with aseptic nipper.Then culture dish is put into to produce to detest and supported foster jar of detesting of mist, place 37 ℃ of incubators to detest foster the cultivation after 48 hours and take out observed result, with the diameter of kind of calliper inhibition zone.Test repeats 3 times.The results are shown in Table 2
The antibacterial circle diameter (mm) that table 2 sample produces lactobacillus (n=3)
4. result and discussion
The gel of the present invention's development is a compound preparation, and the rabbit antifertility result of the test of once carrying out shows that when gel reached 100% contraceptive effect, the Octoxinol concentration in the gel was 14.4mg/ml, and the concentration of cresol sulphur aldehyde is 13mg/ml.This result of the test is that policresulen concentration does not produce inhibition zone to lactobacillus in 4.5～18mg/ml scope.Conclusion: vagina gel of the present invention growth, breeding to the vagina lactobacillus under antifertility dosage is the unrestraint effect.
Three. to the test of vaginal irritation
1. material
1.1 medicine
1. gel of the present invention is pressed embodiment 1 formulation; The Birth Control Institute, Tianjing City provides.
2. blank excipient provides for the Birth Control Institute, Tianjing City.
3. Nonoxynol-9 gel (nonoxynolum gel) is purchased the pharmaceutical Co. Ltd in Chinese Medical Sciences University.Lot number: 050502.。
1.2 animal
16 of female big ear man white rabbits, body weight 2.5-3.0kg, available from Tianjin Chun Le plant, the quality certification number 00666.
2. method
Rabbit is divided into four groups at random, 1. mechanical stimulus group; 2. blank vehicle group; 3. positive drug (happy ether gel) matched group; 4. investigational agent group.Regularly slowly push the vagina depths with special disinfectant glass bushing with gel every day, and the mechanical stimulus group is only with not dosing of glass bushing, and rabbit is dorsal position and puts back to successive administration 7 days after 10 minutes after the administration in special wire mesh cage.In last test back 24h rabbit is put to death dissection, perusal is also write down vaginal congest and the inflammation situation.After rabbit vaginal wall tissue fixed 24 hours with 10% formalin, vaginal wall branch upper, middle and lower three parts are drawn materials, through specimens paraffin embedding slices, HE dyeing (with two kinds of dyeings of h and E), fluorescence microscope is observed down.
The result: the vaginal mucosa pathomorphism changes four kinds of performances: 1. 2. 3. 4. epithelium ulcer of leukocyte infiltration of edema of the congestion of blood vessel, each part lesion degree is by 4 grades of scorings.Every stimulation degree by the level Four scoring (from anosis fade to the heaviest).The results are shown in Table 3.
Grade form is respectively organized in the test of table 3 vaginal irritation
Estimate: by the scoring of this experimental result as seen, gel of the present invention is 4 to four part pathological changes of vaginal irritation total points, and 0-8 is divided into tolerance interval according to standard, so the test of the vaginal irritation of gel of the present invention is tolerance interval.
Four. antifertility and contraceptive efficacy test
1. material
1.1 medicine
1. gel of the present invention is pressed embodiment 1 preparation; Provide by the Birth Control Institute, Tianjing City.
2. Nonoxynol-9 gel (nonoxynolum gel) is purchased the pharmaceutical Co. Ltd in Chinese Medical Sciences University, lot number: 050502.
1.2 animal
The white big ear rabbit both sexes are available from Tianjin Chun Le plant, body weight 2.5-3.0kg.The quality certification number 00666.
2. method
Conformed after white big ear rabbit is bought for 1 week, be divided into 5 groups at random by body weight, 5 every group is blank group, positive controls, high, normal, basic 3 the dosage groups of gel of the present invention.The blank group gives the gel that equivalent does not have medicine, and positive controls awards happy ether gel 48mg/kg, and the high, medium and low dosage group of gel of the present invention is respectively gel 48mg/kg of the present invention, 24mg/kg, 3 kinds of dosage of 12mg/kg.For urging rabbit to oestrus, every doe only oestruses preceding 24 hours intramuscular injection estradiol benzoate 0.1mg/ of copulation.With homemade glass latex syringe sleeve the gel medicinal liquid is slowly pushed the vagina depths during administration, each group all after administration 10 minutes by 1: 2 ratio and there is the male rabbit of fertility to carry out copulation, copulation was dissected after 21 days, record ovary ovulation point, uterus implantation point, tire number alive, stillborn fetus number and unpregnancy number of animals are also calculated contraceptive prevalence rate, and result of the test is carried out statistical procedures with ins tat software.
Result and conclusion
1. gel of the present invention is to the antifertility action of rabbit
High, medium and low 3 the dosage group ovary ovulation points of gel of the present invention are respectively 10.2 ± 1.3,10.2 ± 1.6 and 10.4 ± 1.5.Positive controls is 10.4 ± 1.1.The blank group is 10.4 ± 2.1.Statistical result shows that respectively to organize rabbit ovary ovulation function normal and do not have group difference, sees Table 4.
The conception control gel agent of table 4 energy deactivation microorganism is to the effect of the antifertility of rabbit.
* compares P＜0.01 with the blank group; * compare P＜0.05 with the blank group
The same uterus with positive controls of gel high dose group of the present invention implantation point is zero, in, low dose group is respectively 2.2 ± 4.9 and 6.0 ± 3.7, the blank group is 8.2 ± 1.9.High dose group is compared the difference (P＜0.01) that highly significant is arranged with the blank group, middle dosage group is compared with the blank group has only significant difference (P＜0.05), and low dose group is compared no significant difference (P＞0.05) with the blank group, see Table 2
Gel high dose group of the present invention is the same with positive controls does not all have stillborn fetus, and middle dosage group has only an animal that tire alive is arranged, and the tire number of living is 2.2 ± 4.9, and the low dose group animal tire number of living is 6.0 ± 3.7, and the tire number alive of blank group is 8.2 ± 1.9.High, medium and low 3 the dosage groups of gel of the present invention are compared the difference (P＜0.01) that is respectively highly significant on the statistics with the blank group, significant difference (P＜0.05) and no significant difference (P＞0.05) are arranged.Test each group and there is no stillborn fetus, see Table 2.
2. gel of the present invention is to the contraceptive efficacy of rabbit
High, medium and low 3 the dosage group rabbit unpregnancy numbers of gel of the present invention are respectively 5,4 and 1.Contraceptive prevalence rate is respectively 100%, 80% and 20%.Compare the difference (P＜0.01) that is respectively highly significant statistically with the blank group, significant difference (P＜0.05) and no significant difference (P＞0.05) are arranged.See Table 5.
Table 5 gel of the present invention is to the contraceptive efficacy of rabbit.
* compares P＜0.01 with the blank group; * compare P＜0.05 with the blank group
Conclusion: (24-48mg/kg) gel of the present invention has tangible antifertility action and contraceptive efficacy to rabbit under test dose.Identical with the happy ether glue of commercially available pleasure contraceptive effect.
Five. external test of killing essence
For observe can deactivation microorganism the conception control gel agent kill smart effect, we have done the external smart test of killing.
1. medicine and instrument
1.1 medicine
Gel of the present invention is pressed embodiment 1 preparation; Provide by the Birth Control Institute, Tianjing City.
Octoxinol gel (not adding policresulen in embodiment 1 prescription) provides for the Birth Control Institute, Tianjing City.
Nonoxynol-9 (nonoxynolum gel) is purchased in Pharmaceutical Co Ltd, China Univ. of Pharmacy lot number: 050502.。
Seminal fluid: take from the volunteer that ascetic all health has fertility.
1.2 instrument: OLYMPUS CH2 microscope, calorstat, stopwatch etc.
2. method
Gather the Freshman seminal fluid in an ascetic week, treat that its liquefaction back carries out the mensuration of sperm sum and mobility by the specified standard method of WHO, all sums are higher than 20 * 10
6/ ml, activity ratio is used for this test greater than 80%.Improvement Sander-Cramer method is adopted in this test, medicine to be measured and seminal fluid were mixed in 5: 1 by volume, and fully mixing was got a mixed liquor rapidly on microscope slide after 5 seconds, observe continuously 10 high power fields in room temperature (25 ℃) with microscope, write down in 20 seconds and have or not motile sperm.Have motile sperm for (+), no motile sperm be (-), calculate the minimum smart concentration of killing.3 different volunteers' semen sample is adopted in each test, and each test repeats 3 times.Do positive control drug with happy ether.
3. result and discussion
Gel of the present invention is minimum in 20 seconds kills smart concentration and is 0.5mg/ml, identical with the happy ether of positive control drug, and concrete data see Table 6
The external effect of killing essence of table 6 gel.
Annotate: "-" do not have motile sperm in 20 seconds."+" had motile sperm in 20 seconds
Result of the test shows, Octoxinol gel and Nonoxynol-9 be minimum to kill smart concentration and be the smart effect of killing of 0.5mg/ml and gel of the present invention roughly the same.Policresulen does not influence Octoxinol and kills smart effect.
Six. the bactericidal action test
1, sample
Title: gel of the present invention provides by embodiment 1 preparation Birth Control Institute, Tianjing City.
2, culture medium and strain
Culture medium: nutrient broth medium (lot number: 060323)
Nutrient agar (lot number: 060908)
Fungi culture medium (lot number: 071017)
Agar powder (lot number: 060903) be Beijing three medicine scientific and technological development companies and produce
Strain: staphylococcus aureus [CMCC (B) 26003]
Escherichia coli [CMCC (B) 44103]
Candida albicans [CMCC (F) 98001]
All available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute
3, test method
3.1 culture medium preparation: getting above-mentioned nutrient broth medium 4g, to add water to 100ml be extra quality culture medium, and getting above-mentioned nutrient broth medium 2g, to add water to 100ml be pure culture medium; Get above-mentioned fungi culture medium 5.7g, adding water to 100ml is extra quality culture medium, gets above-mentioned fungi culture medium 2.85g, and adding water to 100ml is pure culture medium, 121 ℃ of autoclavings 15 minutes; Get above-mentioned nutrient agar 6.8g and add water to 200ml, get above-mentioned fungi culture medium 5.7g and above-mentioned agar powder 3.8g adds water to 200ml, 121 ℃ of autoclavings 15 minutes, more than each culture medium inject plate when placing about 50 ℃, the about 20ml of each plate, standby after solidifying.
3.2 the preparation of bacteria suspension: Nutrient agar culture 1 oese of getting above-mentioned staphylococcus aureus, escherichia coli is inoculated in the 15ml bactericidal nurishing broth bouillon 35 ℃ respectively and cultivated 24 hours; Fungi agar medium culture 1 oese of getting above-mentioned Candida albicans is inoculated in the 15ml sterilization fungi culture medium 25 ℃ and cultivates 48 hours as original bacteria liquid, gets each original bacteria liquid 1ml and sterilizes in the 0.9% sodium chloride solution test tube as 10 to filling 9ml respectively
-1Bacterium liquid waits doubly to be diluted to 10
-6, bacteria containing amount is 50～100cfu/ml, and is standby.
3.3 sample treatment: get each 3 parts of gel 2ml, 2 parts add to respectively in the sterile tube that contains extra quality nutrient broth medium 2ml, and 1 part adds in the sterile tube that contains extra quality fungi culture medium 2ml, and mixing is first pipe, and concentration is 0.9%; Get the corresponding first pipe solution 2ml respectively to the sterile tube that contains pure nutrient broth medium 2ml and contain in the sterile tube of pure fungi culture medium 2ml, mixing is second pipe, and concentration is 0.45%; With 11 pipes of method doubling dilution to the successively, the concentration of the 3rd pipe to the 11 pipes is respectively 0.225%, 0.1125%, 0.05625%, 0.02812%, 0.01406%, 0.00703%, 0.00352%, 0.00176% and 0.00088%.It is 10 that one group of every pipe in the nutrient broth medium multiple proportions series pipe adds bacteria containing amount respectively
-6A dilution level staphylococcus aureus bacterium liquid 0.1ml, another organizes every pipe, and to add bacteria containing amount respectively be 10
-6Dilution level escherichia coli bacterium liquid 0.1ml cultivated 24 hours for 35 ℃; Every pipe adds respectively and is diluted to 10 in the fungi culture medium multiple proportions series pipe
-6Candida albicans bacterium liquid 0.1ml, cultivated 48 hours for 25 ℃.Do positive control (the 12nd pipe adds contrast bacterium 0.1ml respectively among the culture medium 2ml), negative control (the 13rd pipe, culture medium 2ml) and blank gel contrast (the 14th pipe adds contrast bacterium 0.1ml in blank gel of 1ml and the extra quality culture medium of 1ml) simultaneously.
4, result of the test
The sterilization experimental data sees Table 7
Table 7 gel bactericidal effect data
Annotate :-expression asepsis growth; + expression has bacteria growing; * represent minimum bactericidal concentration; # represents minimum inhibitory concentration
With preceding 5 pipes of the staphylococcus aureus pipe of not seeing bacterial growth, preceding 4 each 0.1ml of pipe culture of escherichia coli pipe add respectively in the Nutrient agar plate, smear evenly with the sterilization rod, cultivate 24 hours for 35 ℃; 3 pipe culture 0.1ml before not seeing the Candida albicans of bacterial growth are added respectively in the mycobiotic agar plate, smear evenly, 25 ℃ of cultivations 48 hours with the sterilization rod.Clump count on the plate is minimum bactericidal concentration (being respectively staphylococcus aureus the 5th pipe, escherichia coli the 3rd pipe and Candida albicans the 2nd pipe) less than 5 minimum dilution drug level, sees Table 8
5, conclusion
This test repeats 2 times, comes to the same thing.
Table 8 minimum bactericidal concentration and minimum inhibitory concentration
Blank gel contrast is noiseless to this test.
Seven, the external infusorian test (can simplify) extremely of microbicidel conception control gel agent
1 material
The worm strain: trichomonal vaginitis is collected in gynecological of Tianjin Nankai Hospital
Culture medium: parasitology teaching and research room of Medical University Of Tianjin preparation
Sample: 1. embodiment 1 preparation is pressed in the agent of microbicidel conception control gel
2. solution (not containing gel-type vehicle)
3. tinidazole injection lot number 070731
2 test methods
2.1 preparation trichomonacide liquid: cultivate 800～1000 active polypide/0.1ml.
2.2 trial drug preparation: trial drug respectively by 1: 1,1: 2,1: 4, is diluted at 1: 8.
2.3 take a sample respectively by the listed time period of form, low power lens is observed the polypide active situation down, and high power lens is observed the polypide metamorphosis down.
3 insecticidal effect criterion
1. active, the form good (-) of polypide; 2. polypide fine motion, form normal (±); 3. polypide inertia, form become circle (+); 4. complete, the granulating (++) of polypide; 5. polypide cracking (+++)
4 result of the tests
Pressed down the worm degree 1: 1 10 minutes 4.1 gel is minimum,
Minimum parasite killing degree 1: 1 30 minutes
Pressed down the worm degree 1: 8 10 minutes 4.2 solution is minimum
Minimum parasite killing degree 1: 8 30 minutes
Result of the test shows, gel can satisfy during administration 10min and kill infusorian under the design dosage.
Eight, the external effect of directly killing the virus of gel
The dilution medicine 100 μ l of difference are mixed in the EP pipe with 100 μ l HIV supernatants, positive drug sodium hypochlorite, negative control and positive control hole are set simultaneously, hatch 0min, 5min, 10min, 30min taking-up under the room temperature, inhale the above-mentioned mixed liquor of 1 μ l in 96 orifice plates of the C8166 cell that has added 4 * 104/ holes, 37 ℃, cultivate (100 *) counting syncytium number under three days inverted microscopes in the 5%CO2 incubator, calculate suppression ratio (%).Result of the test shows: gel is when 1% concentration, and 10min and 30min suppression ratio about 90% show stronger direct viricidal effect.
Nine, anti-Neisseria of external anti-gonorrhea and anti-Ureaplasma urealyticum test
Result of the test shows that gel also has anti-Neisseria of tangible anti-gonorrhea and anti-Ureaplasma urealyticum active function under the design dosage.
Embodiment 2
Raw material
Carboxymethyl cellulose, propylene glycol, glycerol, potassium sorbate are all commercially available; Policresulen: Qihe synthetic Fine Chemical Co., Ltd in Jinan provides lot number: 050802; Octoxinol: Sigma's aldrich: (Shanghai) trading company (ICEPL CA 630) provide lot number: 075K0071.Purified water: self-control.
Prescription
Carboxymethyl cellulose 3.0g
Propylene glycol 1.0g
Glycerol 1.0g
Policresulen 1.8g
Octoxinol 2.0g
Sodium benzoate 0.15g
Purified water is an amount of
Total amount 100g
Preparation method is with embodiment 1
Claims (4)
1. contraceptive vagina gel with function of killing microorganism, the component that it is characterized in that this gel comprises spermicide, antibacterial, substrate, wetting agent, antiseptic and water, and make gel: substrate is added in the wetting agent by following steps, stir while adding and make it to be uniformly dispersed, add spermicide again, stir; Get antibacterial, antiseptic and add in the purified water of preparation amount and stir into homogeneous solution, more than two kinds of solution mix, stir the back deaeration and promptly make gel.
2. the contraceptive vagina gel with function of killing microorganism according to claim 1, the proportioning that it is characterized in that this gel raw material weight percentage ratio is as follows: spermicide 0.1～5, antibacterial 0.1～3, substrate 1～10, wetting agent 1～50, antiseptic 0.01～0.5, surplus are purified water.
3. the contraceptive vagina gel with function of killing microorganism according to claim 1, the proportioning that it is characterized in that this gel raw material weight percentage ratio is as follows: spermicide 2, antibacterial 1.8, substrate 5, wetting agent 20, antiseptic 0.15, surplus are purified water.
4. the contraceptive vagina gel with function of killing microorganism according to claim 1, it is characterized in that spermicide is selected from a kind of in nonoxynolum and the Octoxinol, antibacterial is selected from policresulen, ketoconazole, metronidazole and the tinidazole any one or two kinds.Substrate is selected from sodium carboxymethyl cellulose, sodium alginate, poly-chitose, polyvinylpyrrolidone and the hydroxypropyl emthylcellulose any one or two kinds, and wetting agent is selected from propylene glycol, glycerol and the Polyethylene Glycol any one or two kinds of.Antiseptic is selected from sorbic acid, potassium sorbate, benzoic acid, sodium benzoate and the parabens any one or two kinds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100535627A CN101606902A (en) | 2008-06-19 | 2008-06-19 | Contraceptive vagina gel with function of killing microorganism |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100535627A CN101606902A (en) | 2008-06-19 | 2008-06-19 | Contraceptive vagina gel with function of killing microorganism |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101606902A true CN101606902A (en) | 2009-12-23 |
Family
ID=41480918
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008100535627A Pending CN101606902A (en) | 2008-06-19 | 2008-06-19 | Contraceptive vagina gel with function of killing microorganism |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101606902A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106727849A (en) * | 2017-01-22 | 2017-05-31 | 李忠泽 | A kind of gynecological gel |
| CN107811964A (en) * | 2016-09-09 | 2018-03-20 | 国家卫生计生委科学技术研究所 | Antibacterial conception control gel that is biodegradable and realizing dosed administration |
| CN109730985A (en) * | 2019-03-27 | 2019-05-10 | 丹东欣时代生物医药科技有限公司 | A kind of production method of conception control gel |
| CN109745300A (en) * | 2019-02-02 | 2019-05-14 | 沈阳得康医药科技有限公司 | Physics conception control gel film forming agent without spermicide |
| CN110051657A (en) * | 2013-09-24 | 2019-07-26 | 上海市计划生育科学研究所 | Uses of Mandelic Acid |
| CN111012902A (en) * | 2020-01-17 | 2020-04-17 | 金方卓越(厦门)生物科技有限公司 | Female antibacterial contraception maintenance gel and preparation method thereof |
| CN114903918A (en) * | 2022-05-27 | 2022-08-16 | 北京恩吉赛生物科技有限公司 | Female micro-ecological bacteriostatic restoration gel and preparation method and application thereof |
-
2008
- 2008-06-19 CN CNA2008100535627A patent/CN101606902A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051657A (en) * | 2013-09-24 | 2019-07-26 | 上海市计划生育科学研究所 | Uses of Mandelic Acid |
| CN107811964A (en) * | 2016-09-09 | 2018-03-20 | 国家卫生计生委科学技术研究所 | Antibacterial conception control gel that is biodegradable and realizing dosed administration |
| CN106727849A (en) * | 2017-01-22 | 2017-05-31 | 李忠泽 | A kind of gynecological gel |
| CN109745300A (en) * | 2019-02-02 | 2019-05-14 | 沈阳得康医药科技有限公司 | Physics conception control gel film forming agent without spermicide |
| CN109745300B (en) * | 2019-02-02 | 2023-01-03 | 沈阳得康医药科技有限公司 | Physical contraceptive gel film-forming agent without spermicide |
| CN109730985A (en) * | 2019-03-27 | 2019-05-10 | 丹东欣时代生物医药科技有限公司 | A kind of production method of conception control gel |
| CN111012902A (en) * | 2020-01-17 | 2020-04-17 | 金方卓越(厦门)生物科技有限公司 | Female antibacterial contraception maintenance gel and preparation method thereof |
| CN111012902B (en) * | 2020-01-17 | 2022-06-03 | 金方卓越(厦门)生物科技有限公司 | Female antibacterial contraception maintenance gel and preparation method thereof |
| CN114903918A (en) * | 2022-05-27 | 2022-08-16 | 北京恩吉赛生物科技有限公司 | Female micro-ecological bacteriostatic restoration gel and preparation method and application thereof |
| CN114903918B (en) * | 2022-05-27 | 2024-04-16 | 北京恩吉赛生物科技有限公司 | Female micro-ecological antibacterial restoration gel, and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3777499B2 (en) | Antifungal composition | |
| CN101606902A (en) | Contraceptive vagina gel with function of killing microorganism | |
| CN1431895A (en) | Compsns-and methods for trapping and inactivating pathogenic microbes and spermatozoa | |
| CN104398500A (en) | Antimicrobial compositions and methods | |
| CN1084612C (en) | Viracidal, bactericidal and spermicidal vaginal suppository | |
| CN102470117A (en) | Composition comprising benzoic acid in combination with organic acid preservatives as active components and use thereof | |
| CN109620798A (en) | An antibacterial and antibacterial intimate care gel for anti-gynecological diseases | |
| CN101099735B (en) | Wide-spectrum high-efficient microorganism killing agent | |
| CN118845629B (en) | Chitosan copper ion composite hydrogel, preparation method and application | |
| CN106421217A (en) | Benzalkonium chloride solution and preparation method thereof | |
| CN100457084C (en) | Nanometer silver type external use antibiotic gel for female external use and its prepn. method | |
| CN108404111B (en) | A bacteriostatic and antiviral preparation containing semen Phaseoli vulgaris phytohemagglutinin as main ingredient | |
| CN102048729B (en) | Preparation for treating vaginitis | |
| CN109432201A (en) | Gynaecologic antibiotic gel and preparation method thereof | |
| CN119950416A (en) | A kind of andrographolide gel and its preparation method and application | |
| CN111329846A (en) | Vaginal sterilization adhesive film and preparation method thereof | |
| CN106267329A (en) | A kind of plants essential oil gel dressing and its preparation method and application | |
| CN101933895A (en) | Fenticonazole nitrate vaginal suppository composition | |
| CN101327304A (en) | Use of Ningbingtai in medicament for treating gynecology inflammation | |
| CN101766813A (en) | Suppository for treating mammalian endometritis and preparation method thereof | |
| CN101450082B (en) | Medicine for treating vaginal diseases by using biological viable bacteria | |
| CN109771595A (en) | A kind of Chinese medicine composition and preparation method thereof for treating gynaecological imflammation | |
| CN103127490B (en) | Medicinal composition for treating vulvovaginal candidiasis | |
| CN101612392A (en) | A kind ofly be used to prevent and treat preparation of mammalian endometritis and preparation method thereof | |
| AU2021104085A4 (en) | Hpv-resistant lactic acid bacteria gynecological preparation and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20091223 |