CN1444926A - 生物粘着性药物释放系统 - Google Patents
生物粘着性药物释放系统 Download PDFInfo
- Publication number
- CN1444926A CN1444926A CN02127087A CN02127087A CN1444926A CN 1444926 A CN1444926 A CN 1444926A CN 02127087 A CN02127087 A CN 02127087A CN 02127087 A CN02127087 A CN 02127087A CN 1444926 A CN1444926 A CN 1444926A
- Authority
- CN
- China
- Prior art keywords
- medicine
- agent
- therapeutic activity
- described compositions
- mutually
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 241
- 229940079593 drug Drugs 0.000 title claims abstract description 41
- 230000002378 acidificating effect Effects 0.000 claims abstract description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 43
- 238000012377 drug delivery Methods 0.000 claims abstract description 42
- 230000007935 neutral effect Effects 0.000 claims abstract description 37
- 239000000839 emulsion Substances 0.000 claims abstract description 33
- 230000001225 therapeutic effect Effects 0.000 claims description 106
- 239000000203 mixture Substances 0.000 claims description 99
- 239000000872 buffer Substances 0.000 claims description 91
- -1 antimicrobial Substances 0.000 claims description 60
- 239000003795 chemical substances by application Substances 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 24
- 210000001215 vagina Anatomy 0.000 claims description 22
- 239000000463 material Substances 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 16
- 230000003204 osmotic effect Effects 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 14
- 229940121375 antifungal agent Drugs 0.000 claims description 11
- 210000004877 mucosa Anatomy 0.000 claims description 11
- 150000003851 azoles Chemical class 0.000 claims description 10
- 229960000282 metronidazole Drugs 0.000 claims description 10
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 10
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 9
- 230000000844 anti-bacterial effect Effects 0.000 claims description 9
- 230000036541 health Effects 0.000 claims description 9
- 229910017604 nitric acid Inorganic materials 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 9
- 230000000843 anti-fungal effect Effects 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 8
- 239000002502 liposome Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 239000000934 spermatocidal agent Substances 0.000 claims description 8
- 239000003098 androgen Substances 0.000 claims description 7
- 230000000845 anti-microbial effect Effects 0.000 claims description 7
- 239000003443 antiviral agent Substances 0.000 claims description 7
- 239000007952 growth promoter Substances 0.000 claims description 7
- 229920001282 polysaccharide Polymers 0.000 claims description 7
- 239000005017 polysaccharide Substances 0.000 claims description 7
- BLSQLHNBWJLIBQ-OZXSUGGESA-N (2R,4S)-terconazole Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2N=CN=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 BLSQLHNBWJLIBQ-OZXSUGGESA-N 0.000 claims description 6
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[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 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 6
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 150000002430 hydrocarbons Chemical class 0.000 claims description 6
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 6
- 229960000580 terconazole Drugs 0.000 claims description 6
- 229920002101 Chitin Polymers 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- UFUVLHLTWXBHGZ-MGZQPHGTSA-N [(2r,3r,4s,5r,6r)-6-[(1s,2s)-2-chloro-1-[[(2s,4r)-1-methyl-4-propylpyrrolidine-2-carbonyl]amino]propyl]-4,5-dihydroxy-2-methylsulfanyloxan-3-yl] dihydrogen phosphate Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@@H](SC)O1 UFUVLHLTWXBHGZ-MGZQPHGTSA-N 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 5
- 229960002227 clindamycin Drugs 0.000 claims description 5
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims description 5
- 229960002291 clindamycin phosphate Drugs 0.000 claims description 5
- 238000009792 diffusion process Methods 0.000 claims description 5
- 239000003995 emulsifying agent Substances 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 239000004014 plasticizer Substances 0.000 claims description 5
- 241000894006 Bacteria Species 0.000 claims description 4
- 208000004926 Bacterial Vaginosis Diseases 0.000 claims description 4
- 229920001503 Glucan Polymers 0.000 claims description 4
- 239000004902 Softening Agent Substances 0.000 claims description 4
- 239000004599 antimicrobial Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 229960005074 butoconazole Drugs 0.000 claims description 4
- SWLMUYACZKCSHZ-UHFFFAOYSA-N butoconazole Chemical compound C1=CC(Cl)=CC=C1CCC(SC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 SWLMUYACZKCSHZ-UHFFFAOYSA-N 0.000 claims description 4
- 229960004022 clotrimazole Drugs 0.000 claims description 4
- 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 claims description 4
- 238000000576 coating method Methods 0.000 claims description 4
- 229960000690 flutrimazole Drugs 0.000 claims description 4
- QHMWCHQXCUNUAK-UHFFFAOYSA-N flutrimazole Chemical compound C1=CC(F)=CC=C1C(N1C=NC=C1)(C=1C(=CC=CC=1)F)C1=CC=CC=C1 QHMWCHQXCUNUAK-UHFFFAOYSA-N 0.000 claims description 4
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 4
- 239000000375 suspending agent Substances 0.000 claims description 4
- 239000000080 wetting agent Substances 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
- MQHLMHIZUIDKOO-OKZBNKHCSA-N (2R,6S)-2,6-dimethyl-4-[(2S)-2-methyl-3-[4-(2-methylbutan-2-yl)phenyl]propyl]morpholine Chemical compound C1=CC(C(C)(C)CC)=CC=C1C[C@H](C)CN1C[C@@H](C)O[C@@H](C)C1 MQHLMHIZUIDKOO-OKZBNKHCSA-N 0.000 claims description 3
- AFNXATANNDIXLG-SFHVURJKSA-N 1-[(2r)-2-[(4-chlorophenyl)methylsulfanyl]-2-(2,4-dichlorophenyl)ethyl]imidazole Chemical compound C1=CC(Cl)=CC=C1CS[C@H](C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 AFNXATANNDIXLG-SFHVURJKSA-N 0.000 claims description 3
- LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 claims description 3
- QXHHHPZILQDDPS-UHFFFAOYSA-N 1-{2-[(2-chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound S1C=CC(COC(CN2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1Cl QXHHHPZILQDDPS-UHFFFAOYSA-N 0.000 claims description 3
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 claims description 3
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 3
- 108010064760 Anidulafungin Proteins 0.000 claims description 3
- 108010020326 Caspofungin Proteins 0.000 claims description 3
- 229930186147 Cephalosporin Natural products 0.000 claims description 3
- 241000606161 Chlamydia Species 0.000 claims description 3
- 108090000695 Cytokines Proteins 0.000 claims description 3
- 102000004127 Cytokines Human genes 0.000 claims description 3
- 241000194033 Enterococcus Species 0.000 claims description 3
- 241000588724 Escherichia coli Species 0.000 claims description 3
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 3
- 229930182566 Gentamicin Natural products 0.000 claims description 3
- CTETYYAZBPJBHE-UHFFFAOYSA-N Haloprogin Chemical compound ClC1=CC(Cl)=C(OCC#CI)C=C1Cl CTETYYAZBPJBHE-UHFFFAOYSA-N 0.000 claims description 3
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 3
- 108060003100 Magainin Proteins 0.000 claims description 3
- 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 claims description 3
- 241000203736 Mobiluncus Species 0.000 claims description 3
- 241000588652 Neisseria gonorrhoeae Species 0.000 claims description 3
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 claims description 3
- 229930182555 Penicillin Natural products 0.000 claims description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 3
- NCXMLFZGDNKEPB-UHFFFAOYSA-N Pimaricin Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCC(C)OC(=O)C=CC2OC2CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 NCXMLFZGDNKEPB-UHFFFAOYSA-N 0.000 claims description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 3
- 208000003251 Pruritus Diseases 0.000 claims description 3
- KGZHFKDNSAEOJX-WIFQYKSHSA-N Ramoplanin Chemical compound C([C@H]1C(=O)N[C@H](CCCN)C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C)C(=O)N[C@H](C(=O)O[C@@H]([C@@H](C(N[C@@H](C(=O)N[C@H](CCCN)C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N1)[C@H](C)O)C=1C=CC(O)=CC=1)C=1C=CC(O)=CC=1)[C@@H](C)O)C=1C=CC(O)=CC=1)=O)NC(=O)[C@H](CC(N)=O)NC(=O)\C=C/C=C/CC(C)C)C(N)=O)C=1C=C(Cl)C(O)=CC=1)C=1C=CC(O)=CC=1)[C@@H](C)O)C=1C=CC(O[C@@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=1)C1=CC=CC=C1 KGZHFKDNSAEOJX-WIFQYKSHSA-N 0.000 claims description 3
- 239000004098 Tetracycline Substances 0.000 claims description 3
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 claims description 3
- 229960004150 aciclovir Drugs 0.000 claims description 3
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 3
- 239000003463 adsorbent Substances 0.000 claims description 3
- 229960003204 amorolfine Drugs 0.000 claims description 3
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B 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/C=C/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)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 3
- 229960003942 amphotericin b Drugs 0.000 claims description 3
- JHVAMHSQVVQIOT-MFAJLEFUSA-N anidulafungin Chemical compound C1=CC(OCCCCC)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=O)N[C@@H]2C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N3C[C@H](C)[C@H](O)[C@H]3C(=O)N[C@H](O)[C@H](O)C2)[C@@H](C)O)[C@H](O)[C@@H](O)C=2C=CC(O)=CC=2)[C@@H](C)O)=O)C=C1 JHVAMHSQVVQIOT-MFAJLEFUSA-N 0.000 claims description 3
- 229960003348 anidulafungin Drugs 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 230000002725 anti-mycoplasma Effects 0.000 claims description 3
- 239000003429 antifungal agent Substances 0.000 claims description 3
- 108010078256 antimicrobial peptide IB-367 Proteins 0.000 claims description 3
- 239000003904 antiprotozoal agent Substances 0.000 claims description 3
- 229940124522 antiretrovirals Drugs 0.000 claims description 3
- 239000003903 antiretrovirus agent Substances 0.000 claims description 3
- 239000003716 antitrichomonal agent Substances 0.000 claims description 3
- 229960004099 azithromycin Drugs 0.000 claims description 3
- 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 claims description 3
- 239000003124 biologic agent Substances 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 229960002962 butenafine Drugs 0.000 claims description 3
- ABJKWBDEJIDSJZ-UHFFFAOYSA-N butenafine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)CC1=CC=C(C(C)(C)C)C=C1 ABJKWBDEJIDSJZ-UHFFFAOYSA-N 0.000 claims description 3
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 claims description 3
- JYIKNQVWKBUSNH-WVDDFWQHSA-N caspofungin Chemical compound C1([C@H](O)[C@@H](O)[C@H]2C(=O)N[C@H](C(=O)N3CC[C@H](O)[C@H]3C(=O)N[C@H](NCCN)[C@H](O)C[C@@H](C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N2)[C@@H](C)O)=O)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)[C@H](O)CCN)=CC=C(O)C=C1 JYIKNQVWKBUSNH-WVDDFWQHSA-N 0.000 claims description 3
- 229960003034 caspofungin Drugs 0.000 claims description 3
- 229960002682 cefoxitin Drugs 0.000 claims description 3
- 229960004755 ceftriaxone Drugs 0.000 claims description 3
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims description 3
- 229940124587 cephalosporin Drugs 0.000 claims description 3
- 150000001780 cephalosporins Chemical class 0.000 claims description 3
- 230000000973 chemotherapeutic effect Effects 0.000 claims description 3
- SCKYRAXSEDYPSA-UHFFFAOYSA-N ciclopirox Chemical compound ON1C(=O)C=C(C)C=C1C1CCCCC1 SCKYRAXSEDYPSA-UHFFFAOYSA-N 0.000 claims description 3
- 229960002626 clarithromycin Drugs 0.000 claims description 3
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 3
- 239000003433 contraceptive agent Substances 0.000 claims description 3
- 230000002254 contraceptive effect Effects 0.000 claims description 3
- 229960002488 dalbavancin Drugs 0.000 claims description 3
- 108700009376 dalbavancin Proteins 0.000 claims description 3
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 claims description 3
- 229960000766 danazol Drugs 0.000 claims description 3
- KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical compound C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 claims description 3
- 229960003913 econazole Drugs 0.000 claims description 3
- 229960003276 erythromycin Drugs 0.000 claims description 3
- 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 claims description 3
- GSTNAAOCEHQZDY-UHFFFAOYSA-N formic acid phosphane Chemical class [PH4+].[O-]C=O GSTNAAOCEHQZDY-UHFFFAOYSA-N 0.000 claims description 3
- 239000003205 fragrance Substances 0.000 claims description 3
- 229960002963 ganciclovir Drugs 0.000 claims description 3
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 3
- 229960001906 haloprogin Drugs 0.000 claims description 3
- 230000003054 hormonal effect Effects 0.000 claims description 3
- 230000006872 improvement Effects 0.000 claims description 3
- GUCYBPFJNGVFEB-XELKFLSISA-N iseganan Chemical compound C([C@H]1C(=O)N[C@H]2CSSC[C@H](NC(=O)[C@H](CC=3C=CC=CC=3)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(N1)=O)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@@H](N)CCCNC(N)=N)CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(C)C)C1=CC=C(O)C=C1 GUCYBPFJNGVFEB-XELKFLSISA-N 0.000 claims description 3
- 229950000488 iseganan Drugs 0.000 claims description 3
- 229960004125 ketoconazole Drugs 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 229960002509 miconazole Drugs 0.000 claims description 3
- OZGNYLLQHRPOBR-DHZHZOJOSA-N naftifine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)C\C=C\C1=CC=CC=C1 OZGNYLLQHRPOBR-DHZHZOJOSA-N 0.000 claims description 3
- 229960004313 naftifine Drugs 0.000 claims description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 3
- 150000002790 naphthalenes Chemical class 0.000 claims description 3
- 229960003255 natamycin Drugs 0.000 claims description 3
- NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin 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/C[C@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 claims description 3
- 229940087419 nonoxynol-9 Drugs 0.000 claims description 3
- 229920004918 nonoxynol-9 Polymers 0.000 claims description 3
- 108020004707 nucleic acids Proteins 0.000 claims description 3
- 102000039446 nucleic acids Human genes 0.000 claims description 3
- 150000007523 nucleic acids Chemical class 0.000 claims description 3
- 239000002777 nucleoside Substances 0.000 claims description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 3
- 229960000988 nystatin Drugs 0.000 claims description 3
- 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 claims description 3
- 229960002894 oxiconazole nitrate Drugs 0.000 claims description 3
- WVNOAGNOIPTWPT-NDUABGMUSA-N oxiconazole nitrate Chemical compound O[N+]([O-])=O.ClC1=CC(Cl)=CC=C1CO\N=C(C=1C(=CC(Cl)=CC=1)Cl)/CN1C=NC=C1 WVNOAGNOIPTWPT-NDUABGMUSA-N 0.000 claims description 3
- 229960001179 penciclovir Drugs 0.000 claims description 3
- 229940049954 penicillin Drugs 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- 239000013612 plasmid Substances 0.000 claims description 3
- KQOXLKOJHVFTRN-UHFFFAOYSA-N pleconaril Chemical compound O1N=C(C)C=C1CCCOC1=C(C)C=C(C=2N=C(ON=2)C(F)(F)F)C=C1C KQOXLKOJHVFTRN-UHFFFAOYSA-N 0.000 claims description 3
- 229960000471 pleconaril Drugs 0.000 claims description 3
- 150000004291 polyenes Chemical class 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 claims description 3
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 3
- 229930185107 quinolinone Natural products 0.000 claims description 3
- 229950003551 ramoplanin Drugs 0.000 claims description 3
- 108010076689 ramoplanin Proteins 0.000 claims description 3
- 239000012744 reinforcing agent Substances 0.000 claims description 3
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- 229960002607 sulconazole Drugs 0.000 claims description 3
- 150000003457 sulfones Chemical class 0.000 claims description 3
- 239000012622 synthetic inhibitor Substances 0.000 claims description 3
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 claims description 3
- 229960003604 testosterone Drugs 0.000 claims description 3
- 229960002180 tetracycline Drugs 0.000 claims description 3
- 229930101283 tetracycline Natural products 0.000 claims description 3
- 235000019364 tetracycline Nutrition 0.000 claims description 3
- 150000003522 tetracyclines Chemical class 0.000 claims description 3
- 229960004214 tioconazole Drugs 0.000 claims description 3
- 230000009261 transgenic effect Effects 0.000 claims description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 3
- 229960004319 trichloroacetic acid Drugs 0.000 claims description 3
- 239000000814 tuberculostatic agent Substances 0.000 claims description 3
- 229940075466 undecylenate Drugs 0.000 claims description 3
- 229960005486 vaccine Drugs 0.000 claims description 3
- 229940093257 valacyclovir Drugs 0.000 claims description 3
- KGPGQDLTDHGEGT-JCIKCJKQSA-N zeven Chemical compound C=1C([C@@H]2C(=O)N[C@H](C(N[C@H](C3=CC(O)=C4)C(=O)NCCCN(C)C)=O)[C@H](O)C5=CC=C(C(=C5)Cl)OC=5C=C6C=C(C=5O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@H](O5)C(O)=O)NC(=O)CCCCCCCCC(C)C)OC5=CC=C(C=C5)C[C@@H]5C(=O)N[C@H](C(N[C@H]6C(=O)N2)=O)C=2C(Cl)=C(O)C=C(C=2)OC=2C(O)=CC=C(C=2)[C@H](C(N5)=O)NC)=CC=C(O)C=1C3=C4O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O KGPGQDLTDHGEGT-JCIKCJKQSA-N 0.000 claims description 3
- 241000589220 Acetobacter Species 0.000 claims description 2
- 241000588807 Bordetella Species 0.000 claims description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 2
- 241000193403 Clostridium Species 0.000 claims description 2
- 241000588748 Klebsiella Species 0.000 claims description 2
- 241000204031 Mycoplasma Species 0.000 claims description 2
- 241000607142 Salmonella Species 0.000 claims description 2
- 241000191940 Staphylococcus Species 0.000 claims description 2
- 241000194017 Streptococcus Species 0.000 claims description 2
- 206010047799 Vulvovaginitis trichomonal Diseases 0.000 claims description 2
- 230000008595 infiltration Effects 0.000 claims description 2
- 238000001764 infiltration Methods 0.000 claims description 2
- 239000004576 sand Substances 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- WZOZEZRFJCJXNZ-ZBFHGGJFSA-N cefoxitin Chemical compound N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)CC1=CC=CS1 WZOZEZRFJCJXNZ-ZBFHGGJFSA-N 0.000 claims 2
- 150000004676 glycans Chemical class 0.000 claims 2
- 239000011149 active material Substances 0.000 abstract 1
- 239000012071 phase Substances 0.000 description 36
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 32
- 239000008384 inner phase Substances 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 18
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 15
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 13
- 150000002632 lipids Chemical class 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 230000003213 activating effect Effects 0.000 description 9
- 235000014113 dietary fatty acids Nutrition 0.000 description 9
- 229930195729 fatty acid Natural products 0.000 description 9
- 239000000194 fatty acid Substances 0.000 description 9
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 235000010445 lecithin Nutrition 0.000 description 8
- 239000000787 lecithin Substances 0.000 description 8
- 229940067606 lecithin Drugs 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 230000006641 stabilisation Effects 0.000 description 8
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 150000003904 phospholipids Chemical class 0.000 description 7
- 210000000582 semen Anatomy 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 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 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229940050410 gluconate Drugs 0.000 description 6
- 229930182480 glucuronide Natural products 0.000 description 6
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 6
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 6
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 5
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 5
- 239000004372 Polyvinyl alcohol Substances 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 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 5
- 235000010443 alginic acid Nutrition 0.000 description 5
- 229920000615 alginic acid Polymers 0.000 description 5
- 239000000783 alginic acid Substances 0.000 description 5
- 229960001126 alginic acid Drugs 0.000 description 5
- 150000004781 alginic acids Chemical class 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
- 150000004804 polysaccharides Chemical class 0.000 description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 description 5
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 229960004063 propylene glycol Drugs 0.000 description 5
- 235000013772 propylene glycol Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 229940032147 starch Drugs 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000008117 stearic acid Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 4
- GMBQZIIUCVWOCD-UQHLGXRBSA-N (25R)-5beta-spirostan-3beta-ol Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 GMBQZIIUCVWOCD-UQHLGXRBSA-N 0.000 description 4
- 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 description 4
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 229930091371 Fructose Natural products 0.000 description 4
- 239000005715 Fructose Substances 0.000 description 4
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 4
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 4
- 229940105329 carboxymethylcellulose Drugs 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 4
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 4
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- PCMORTLOPMLEFB-ONEGZZNKSA-N sinapic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-ONEGZZNKSA-N 0.000 description 4
- 235000010413 sodium alginate Nutrition 0.000 description 4
- 239000000661 sodium alginate Substances 0.000 description 4
- 229940005550 sodium alginate Drugs 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 239000007762 w/o emulsion Substances 0.000 description 4
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 3
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 3
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 241000499489 Castor canadensis Species 0.000 description 3
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 3
- 239000004375 Dextrin Substances 0.000 description 3
- 229920001353 Dextrin Polymers 0.000 description 3
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 235000011779 Menyanthes trifoliata Nutrition 0.000 description 3
- 241001597008 Nomeidae Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- 239000012867 bioactive agent Substances 0.000 description 3
- 230000035587 bioadhesion Effects 0.000 description 3
- 230000003139 buffering effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 235000019425 dextrin Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 3
- 235000013773 glyceryl triacetate Nutrition 0.000 description 3
- 229930182470 glycoside Natural products 0.000 description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 3
- 238000000265 homogenisation Methods 0.000 description 3
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 3
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 3
- 229960000201 isosorbide dinitrate Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 229950008882 polysorbate Drugs 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 3
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 3
- 229960003415 propylparaben Drugs 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 3
- 239000004299 sodium benzoate Substances 0.000 description 3
- 235000010234 sodium benzoate Nutrition 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229920001059 synthetic polymer Polymers 0.000 description 3
- 229960002622 triacetin Drugs 0.000 description 3
- 210000004291 uterus Anatomy 0.000 description 3
- 229920001285 xanthan gum Polymers 0.000 description 3
- 235000010493 xanthan gum Nutrition 0.000 description 3
- 239000000230 xanthan gum Substances 0.000 description 3
- 229940082509 xanthan gum Drugs 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- OEANUJAFZLQYOD-CXAZCLJRSA-N (2r,3s,4r,5r,6r)-6-[(2r,3r,4r,5r,6r)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](OC)O[C@H](CO)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](OC)[C@H](C(O)=O)O1 OEANUJAFZLQYOD-CXAZCLJRSA-N 0.000 description 2
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KIHBGTRZFAVZRV-UHFFFAOYSA-N 2-Hydroxyoctadecanoic acid Natural products CCCCCCCCCCCCCCCCC(O)C(O)=O KIHBGTRZFAVZRV-UHFFFAOYSA-N 0.000 description 2
- XPCTZQVDEJYUGT-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-pyrone Chemical compound CC=1OC=CC(=O)C=1O XPCTZQVDEJYUGT-UHFFFAOYSA-N 0.000 description 2
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 2
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 2
- BHYOQNUELFTYRT-UHFFFAOYSA-N Cholesterol sulfate Natural products C1C=C2CC(OS(O)(=O)=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 BHYOQNUELFTYRT-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 229920000045 Dermatan sulfate Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 201000009273 Endometriosis Diseases 0.000 description 2
- 229920000855 Fucoidan Polymers 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 2
- 229920002774 Maltodextrin Polymers 0.000 description 2
- 239000005913 Maltodextrin Substances 0.000 description 2
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 2
- 229920002230 Pectic acid Polymers 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 description 2
- GMBQZIIUCVWOCD-WWASVFFGSA-N Sarsapogenine Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 GMBQZIIUCVWOCD-WWASVFFGSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 238000005411 Van der Waals force Methods 0.000 description 2
- 229920002494 Zein Polymers 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 229960002903 benzyl benzoate Drugs 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- BHYOQNUELFTYRT-DPAQBDIFSA-N cholesterol sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 BHYOQNUELFTYRT-DPAQBDIFSA-N 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229940096516 dextrates Drugs 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 238000007046 ethoxylation reaction Methods 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 229940014259 gelatin Drugs 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- 229940097043 glucuronic acid Drugs 0.000 description 2
- 150000002339 glycosphingolipids Chemical class 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 229940058690 lanosterol Drugs 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000395 magnesium oxide Substances 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 235000012245 magnesium oxide Nutrition 0.000 description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 2
- 229940035034 maltodextrin Drugs 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- RZJRJXONCZWCBN-UHFFFAOYSA-N octadecane Chemical compound CCCCCCCCCCCCCCCCCC RZJRJXONCZWCBN-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 210000003101 oviduct Anatomy 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229960005455 polacrilin Drugs 0.000 description 2
- 229960000502 poloxamer Drugs 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 239000010318 polygalacturonic acid Substances 0.000 description 2
- 229920000193 polymethacrylate Polymers 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 2
- 239000000770 propane-1,2-diol alginate Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- PCMORTLOPMLEFB-UHFFFAOYSA-N sinapinic acid Natural products COC1=CC(C=CC(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-UHFFFAOYSA-N 0.000 description 2
- 229950002323 smilagenin Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 238000009331 sowing Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N trilaurin Chemical compound CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 2
- DUXYWXYOBMKGIN-UHFFFAOYSA-N trimyristin Chemical compound CCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCC DUXYWXYOBMKGIN-UHFFFAOYSA-N 0.000 description 2
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- 229940099259 vaseline Drugs 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229940093612 zein Drugs 0.000 description 2
- 239000005019 zein Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- OQQOAWVKVDAJOI-UHFFFAOYSA-N (2-dodecanoyloxy-3-hydroxypropyl) dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCC OQQOAWVKVDAJOI-UHFFFAOYSA-N 0.000 description 1
- FROLUYNBHPUZQU-IIZJPUEISA-N (2R,3R,4S,5R)-2-(hydroxymethyl)-6-[3-[3-[(3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropoxy]propoxy]oxane-3,4,5-triol Chemical compound OC[C@H]1OC(OCCCOCCCOC2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@H]1O FROLUYNBHPUZQU-IIZJPUEISA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NTWLPZMPTFQYQI-UHFFFAOYSA-N (3alpha)-olean-12-ene-3,23-diol Natural products C1CC(O)C(C)(CO)C2CCC3(C)C4(C)CCC5(C)CCC(C)(C)CC5C4=CCC3C21C NTWLPZMPTFQYQI-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GYVJGLPVHBCECZ-RZLHGTIFSA-N (e)-2-octadecylbut-2-enedioic acid;sodium Chemical compound [Na].CCCCCCCCCCCCCCCCCC\C(C(O)=O)=C/C(O)=O GYVJGLPVHBCECZ-RZLHGTIFSA-N 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 1
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 1
- AFSHUZFNMVJNKX-LLWMBOQKSA-N 1,2-dioleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCC\C=C/CCCCCCCC AFSHUZFNMVJNKX-LLWMBOQKSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- 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 description 1
- YUORFOKCGHOEIV-UHFFFAOYSA-N 2-(2,3-dihydroxypropyl)octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)CC(O)CO YUORFOKCGHOEIV-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- NINCFRRECKAMLC-UHFFFAOYSA-N 24alpha-methylzymosterol acetate Natural products CC12CCC(OC(C)=O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C NINCFRRECKAMLC-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 206010059313 Anogenital warts Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000223678 Aureobasidium pullulans Species 0.000 description 1
- MQTOSJVFKKJCRP-HHZDEWPHSA-N Azythromycin 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-HHZDEWPHSA-N 0.000 description 1
- LVDKZNITIUWNER-UHFFFAOYSA-N Bronopol Chemical compound OCC(Br)(CO)[N+]([O-])=O LVDKZNITIUWNER-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- SFSFKDYZVNYCCN-UHFFFAOYSA-N C(O)CN.P(=O)(O)(O)OCC(COCCCCCCCCCCCCCCCC)OCCCCCCCCCCCCCCCC Chemical compound C(O)CN.P(=O)(O)(O)OCC(COCCCCCCCCCCCCCCCC)OCCCCCCCCCCCCCCCC SFSFKDYZVNYCCN-UHFFFAOYSA-N 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- IJLBJBCDNYOWPJ-MVMUGOIMSA-N Cholesterol glucuronide Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O IJLBJBCDNYOWPJ-MVMUGOIMSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000000907 Condylomata Acuminata Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
- YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-CBPJZXOFSA-N D-Gulose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-CBPJZXOFSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-WHZQZERISA-N D-aldose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-WHZQZERISA-N 0.000 description 1
- WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
- LKDRXBCSQODPBY-JDJSBBGDSA-N D-allulose Chemical compound OCC1(O)OC[C@@H](O)[C@@H](O)[C@H]1O LKDRXBCSQODPBY-JDJSBBGDSA-N 0.000 description 1
- YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-VANFPWTGSA-N D-mannopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-VANFPWTGSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-NQXXGFSBSA-N D-ribulose Chemical compound OC[C@@H](O)[C@@H](O)C(=O)CO ZAQJHHRNXZUBTE-NQXXGFSBSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-UHFFFAOYSA-N D-threo-2-Pentulose Natural products OCC(O)C(O)C(=O)CO ZAQJHHRNXZUBTE-UHFFFAOYSA-N 0.000 description 1
- YTBSYETUWUMLBZ-QWWZWVQMSA-N D-threose Chemical compound OC[C@@H](O)[C@H](O)C=O YTBSYETUWUMLBZ-QWWZWVQMSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-WUJLRWPWSA-N D-xylulose Chemical compound OC[C@@H](O)[C@H](O)C(=O)CO ZAQJHHRNXZUBTE-WUJLRWPWSA-N 0.000 description 1
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
- UCTLRSWJYQTBFZ-UHFFFAOYSA-N Dehydrocholesterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCCC(C)C)CCC33)C)C3=CC=C21 UCTLRSWJYQTBFZ-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000004145 Endometritis Diseases 0.000 description 1
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 1
- 206010056474 Erythrosis Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 241000207202 Gardnerella Species 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- GCGBHJLBFAPRDB-UHFFFAOYSA-N Hederagenin Natural products CC1(C)CCC2(CCC3(C)C4CCC5C(C)(CO)C(O)CCC5(C)C4CC=C3C2C1)C(=O)O GCGBHJLBFAPRDB-UHFFFAOYSA-N 0.000 description 1
- SHBUUTHKGIVMJT-UHFFFAOYSA-N Hydroxystearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OO SHBUUTHKGIVMJT-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920001202 Inulin Polymers 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 244000147568 Laurus nobilis Species 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930188226 Lysolipin Natural products 0.000 description 1
- HYMLWHLQFGRFIY-UHFFFAOYSA-N Maltol Natural products CC1OC=CC(=O)C1=O HYMLWHLQFGRFIY-UHFFFAOYSA-N 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000605861 Prevotella Species 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 208000007893 Salpingitis Diseases 0.000 description 1
- GCGBHJLBFAPRDB-KCVAUKQGSA-N Scutellaric acid Natural products CC1(C)CC[C@@]2(CC[C@@]3(C)[C@@H]4CC[C@H]5[C@@](C)(CO)[C@H](O)CC[C@]5(C)[C@H]4CC=C3[C@@H]2C1)C(=O)O GCGBHJLBFAPRDB-KCVAUKQGSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- HZYXFRGVBOPPNZ-UHFFFAOYSA-N UNPD88870 Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)=CCC(CC)C(C)C)C1(C)CC2 HZYXFRGVBOPPNZ-UHFFFAOYSA-N 0.000 description 1
- XZTUSOXSLKTKJQ-UHFFFAOYSA-N Uzarigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C1(O)CCC2C1=CC(=O)OC1 XZTUSOXSLKTKJQ-UHFFFAOYSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- ZPVGIKNDGJGLCO-VGAMQAOUSA-N [(2s,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)O[C@@]1([C@]2(CO)[C@H]([C@H](O)[C@@H](CO)O2)O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O ZPVGIKNDGJGLCO-VGAMQAOUSA-N 0.000 description 1
- SZYSLWCAWVWFLT-UTGHZIEOSA-N [(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxolan-2-yl]methyl octadecanoate Chemical compound O([C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@]1(COC(=O)CCCCCCCCCCCCCCCCC)O[C@H](CO)[C@@H](O)[C@@H]1O SZYSLWCAWVWFLT-UTGHZIEOSA-N 0.000 description 1
- BQPPJGMMIYJVBR-VBGFMNGASA-N [(3s,5r,10s,13r,14r,17r)-4,4,10,13,14-pentamethyl-17-[(2r)-6-methylhept-5-en-2-yl]-2,3,5,6,7,11,12,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@]12C)C[C@H](OC(C)=O)C(C)(C)[C@@H]1CCC1=C2CC[C@]2(C)[C@@H]([C@@H](CCC=C(C)C)C)CC[C@]21C BQPPJGMMIYJVBR-VBGFMNGASA-N 0.000 description 1
- PUUPGXQPWDWTPH-GTPODGLVSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] 2-methylpropanoate Chemical compound C1C=C2C[C@@H](OC(=O)C(C)C)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 PUUPGXQPWDWTPH-GTPODGLVSA-N 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- GUBMPMUEZUKTNI-UHFFFAOYSA-N [2-[decyl(hydroxy)phosphoryl]oxy-3-(10-methoxy-10-oxodecoxy)propyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCP(O)(=O)OC(COP([O-])(=O)OCC[N+](C)(C)C)COCCCCCCCCCC(=O)OC GUBMPMUEZUKTNI-UHFFFAOYSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- 150000001323 aldoses Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000002009 allergenic effect Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 229940092782 bentonite Drugs 0.000 description 1
- 229960000686 benzalkonium chloride 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
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical compound OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229960003168 bronopol Drugs 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- WLNARFZDISHUGS-MIXBDBMTSA-N cholesteryl hemisuccinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 WLNARFZDISHUGS-MIXBDBMTSA-N 0.000 description 1
- 229940069078 citric acid / sodium citrate Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 229940013361 cresol Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960000860 dapsone Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960002380 dibutyl phthalate Drugs 0.000 description 1
- XZTUSOXSLKTKJQ-CESUGQOBSA-N digitoxigenin Chemical compound C1([C@H]2CC[C@]3(O)[C@H]4[C@@H]([C@]5(CC[C@H](O)C[C@H]5CC4)C)CC[C@@]32C)=CC(=O)OC1 XZTUSOXSLKTKJQ-CESUGQOBSA-N 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 1
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960000878 docusate sodium Drugs 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- UQPHVQVXLPRNCX-UHFFFAOYSA-N erythrulose Chemical compound OCC(O)C(=O)CO UQPHVQVXLPRNCX-UHFFFAOYSA-N 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 206010016629 fibroma Diseases 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229960003082 galactose Drugs 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- QPJBWNIQKHGLAU-IQZHVAEDSA-N ganglioside GM1 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 QPJBWNIQKHGLAU-IQZHVAEDSA-N 0.000 description 1
- GIVLTTJNORAZON-HDBOBKCLSA-N ganglioside GM2 (18:0) Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 GIVLTTJNORAZON-HDBOBKCLSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 1
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 1
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- PGOYMURMZNDHNS-MYPRUECHSA-N hederagenin Chemical compound C1C[C@H](O)[C@@](C)(CO)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C PGOYMURMZNDHNS-MYPRUECHSA-N 0.000 description 1
- 229920000140 heteropolymer Polymers 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229940072106 hydroxystearate Drugs 0.000 description 1
- 150000002454 idoses Chemical class 0.000 description 1
- ZCTXEAQXZGPWFG-UHFFFAOYSA-N imidurea Chemical compound O=C1NC(=O)N(CO)C1NC(=O)NCNC(=O)NC1C(=O)NC(=O)N1CO ZCTXEAQXZGPWFG-UHFFFAOYSA-N 0.000 description 1
- 229940113174 imidurea Drugs 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940029339 inulin Drugs 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- LDHQCZJRKDOVOX-IHWYPQMZSA-N isocrotonic acid Chemical compound C\C=C/C(O)=O LDHQCZJRKDOVOX-IHWYPQMZSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229960000829 kaolin Drugs 0.000 description 1
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 1
- BJHIKXHVCXFQLS-PQLUHFTBSA-N keto-D-tagatose Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)C(=O)CO BJHIKXHVCXFQLS-PQLUHFTBSA-N 0.000 description 1
- BQINXKOTJQCISL-GRCPKETISA-N keto-neuraminic acid Chemical compound OC(=O)C(=O)C[C@H](O)[C@@H](N)[C@@H](O)[C@H](O)[C@H](O)CO BQINXKOTJQCISL-GRCPKETISA-N 0.000 description 1
- 239000003835 ketolide antibiotic agent Substances 0.000 description 1
- 150000002584 ketoses Chemical class 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- AIHDCSAXVMAMJH-GFBKWZILSA-N levan Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(CO[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 AIHDCSAXVMAMJH-GFBKWZILSA-N 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- NEOMIZJYHXSRLV-UHFFFAOYSA-N lysolipin Chemical compound O1C2=C(OC)C(Cl)=CC=C2C(=O)C2=C1C(OCO1)=C3C1C(OC)C(C=C1C(O)C(N(C(=O)C1=C1O)C)OC)=C1C3=C2O NEOMIZJYHXSRLV-UHFFFAOYSA-N 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940043353 maltol Drugs 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- GTDHYNXLIKNVTJ-UHFFFAOYSA-N n-(1-hydroxy-2-methylpropan-2-yl)octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NC(C)(C)CO GTDHYNXLIKNVTJ-UHFFFAOYSA-N 0.000 description 1
- QHMGJGNTMQDRQA-UHFFFAOYSA-N n-Dotriacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC QHMGJGNTMQDRQA-UHFFFAOYSA-N 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- CERZMXAJYMMUDR-UHFFFAOYSA-N neuraminic acid Natural products NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO CERZMXAJYMMUDR-UHFFFAOYSA-N 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 239000002353 niosome Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
- 229940100243 oleanolic acid Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 208000025661 ovarian cyst Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- VUXSPDNLYQTOSY-UHFFFAOYSA-N phenylmercuric borate Chemical compound OB(O)O[Hg]C1=CC=CC=C1 VUXSPDNLYQTOSY-UHFFFAOYSA-N 0.000 description 1
- 229960000247 phenylmercuric borate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 229940067626 phosphatidylinositols Drugs 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000002378 plant sterols Nutrition 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229950000845 politef Drugs 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 229940051841 polyoxyethylene ether Drugs 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
- RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical compound O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 description 1
- 229960001589 posaconazole Drugs 0.000 description 1
- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000004300 potassium benzoate Substances 0.000 description 1
- 235000010235 potassium benzoate Nutrition 0.000 description 1
- 229940103091 potassium benzoate Drugs 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 description 1
- PHZLMBHDXVLRIX-UHFFFAOYSA-M potassium lactate Chemical compound [K+].CC(O)C([O-])=O PHZLMBHDXVLRIX-UHFFFAOYSA-M 0.000 description 1
- 239000001521 potassium lactate Substances 0.000 description 1
- 235000011085 potassium lactate Nutrition 0.000 description 1
- 229960001304 potassium lactate Drugs 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- UBYZGUWQNIEQMH-SBBOJQDXSA-M potassium;(2s,3s,4s,5r)-2,3,4,5,6-pentahydroxy-6-oxohexanoate Chemical compound [K+].OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O UBYZGUWQNIEQMH-SBBOJQDXSA-M 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000004999 sex organ Anatomy 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- JZNWSCPGTDBMEW-YFKPBYRVSA-N sn-glycero-3-phosphoethanolamine Chemical compound NCCO[P@@](O)(=O)OC[C@@H](O)CO JZNWSCPGTDBMEW-YFKPBYRVSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007944 soluble tablet Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229940032091 stigmasterol Drugs 0.000 description 1
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 1
- 235000016831 stigmasterol Nutrition 0.000 description 1
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical class FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 229960001947 tripalmitin Drugs 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000001757 vomitory effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229920001221 xylan Polymers 0.000 description 1
- 150000004823 xylans Chemical class 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Reproductive Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Diabetes (AREA)
- AIDS & HIV (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及一种新的pH基本为中性的阴道药物释放系统,适于在阴道腔内缓和地释放具有治疗活性的物质。此阴道药物释放系统包含pH基本为中性的乳剂,此乳剂内有含有两相的药球,内相为水溶相,外相为水不溶相或膜,其中水溶性的内相含有一或多种治疗活性药物。本阴道药物释放系统的一个新的方面是内部的水溶相含有酸性缓冲相。
Description
发明所属技术领域
本发明涉及一种新的pH基本为中性的阴道药物释放系统,适于在阴道腔内缓和地释放具有治疗活性的物质,以优化与治疗活性物质相关的治愈率。阴道药物释放系统包含pH基本为中性的乳剂,此乳剂内有含有两相的药球,内相为水溶相,外相为水不溶相或膜,其中水溶性的内相含有一或多种治疗活性药物。本阴道药物释放系统的一个新的方面是内部的水溶相含有酸性缓冲相,它可以为等渗、高渗或低渗。本发明还涉及一种用这些药物释放系统治疗阴道疾病的方法。
发明的背景技术
药物的一个主要类别是用于妇科生殖系统以诊断、预防、减缓、处置及治愈疾病,及防止或促进妊娠。通常这包括活性药物直接释放到阴道腔及其周围。
因为阴道腔处于使其成为疾病和感染的目标的条件下,实现这些治疗剂的释放的系统通常为凝胶、泡沫、霜剂、栓剂和快速溶解的片剂等剂型。这些释放系统,无论制备的配方和方法如何,已证明它们在阴道腔内按控制方式以3个小时或更长的周期释放活性剂的能力方面有一些困难。在延长的时间周期内向此区域释放活性剂是十分困难的。
阴道腔含有分泌腺而显示水性环境,其分泌液产生在4.5-5.5范围内的酸性pH。由于温暖、湿润和黑暗,阴道的环境有助于细菌、真菌、酵母和其他微生物的生长。另外,从生理结构看阴道是月经碎片、性交的残余精液和不良细菌、真菌、酵母及其它微生物的出入通道。例如在性交或在月经棉条插入时,阴道腔也有相当程度的物理变形。
有药物特性的活性剂已被开发,并被批准用于治疗阴道腔的病痛及防止妊娠。这些活性剂包括抗真菌剂、杀精子剂等。然而,由于已知释放系统的不足,难于达到这些活性剂的最优的潜在效果。目前批准或进而适用于阴道腔内的系统在持久释放药物活性剂方面显示出一些困难。对于与美感有关的系统,例如酸化剂和除臭剂也是这样。
现在作为阴道释放系统的大多数凝胶、泡沫剂、霜剂、栓剂和片剂几乎在塞入阴道腔内后立即分解,并在阴道壁有极小的生物粘附。这被认为是由于它们的水混溶性和/或它们在37℃(体温)缺乏物理稳定性。因此,它们由于活性剂快速、不受控制的释放而显示有限的效果。另外,常规的剂型通常有泄漏和滴漏。为使这些快速泄漏减小到最小程度,最常规的剂型是在夜间病人临睡前以俯卧位给药。
一种改进的释放系统将活性剂输送到发挥作用、吸收的部位,或以预定方式使用。这与常规的需要频繁重复给药以达到活性剂的理想水平的立即释放系统形成对照。改进的释放系统的一个优点是,因为阴道腔内的药物水平保持在恒定的等级,所以每天的给药次数少于常规的系统。另外,现有技术的控制释放系统不影响治疗疾病所需的总天数。
改进的药物释放系统的制剂可以采用乳剂。乳剂通常有高的自由能量保护屏障。特别地,本领域将有相对高的水与油的比例,并有高的自由能的乳剂称为“高内相乳剂”(“HIPE’s”)。 HIPE’s已用于多种用途,例如燃料、农业喷雾剂、纺织品印刷、食品、家庭和工业清洁、化妆品和药品,及灭火剂。HIPE’s也用于制备聚合物泡沫类材料。例如,参见美国专利U.S.Patent No.3,988,508(“Lissant”);和美国专利U.S.PatentNo.5,189,070(“Brownscombe等”),将每个都全文结合于此作为参考。
已知HIPE’s的最突出的特点是:在胃肠道和/或消化道的乳剂型分解,并失去内相能量,这使乳剂在粘膜上融合成连续的膜。
本领域已知一些用于输送药物的控制释放乳剂。例如,全文结合于此作为参考的美国专利U.S.Patent No.5,298,246(“Yano等”),公开了通过口服给药促进亲脂性药物吸收能力的水包油型乳剂。通过加入磷酸钠等渗缓冲液(pH7.0)使乳剂保持稳定。
全文结合于此作为参考的美国专利U.S.Patent No.5,622,657(“Takada等”),公开了一种制备能延续释放的微粒制剂的方法。这些制剂可以包括油包水型乳剂,并可以通过阴道给药。
全文结合于此作为参考的美国专利U.S.Patent No.5,733,939(“Fuhrman等”)公开了治疗包括阴道粘膜的粘膜炎症,炎症的常规的药物释放剂型。这些参考文献讨论了有连续气态或液态碳氟化合物相和不连续的水相的凝胶类乳剂。
全文结合于此作为参考的美国专利U.S.Patent No.5,840,744(“Borgman”)公开了一种治疗细菌性阴道炎的非流动的甲硝唑组合物。可以用缓冲剂将此公开的甲硝唑组合物调节到酸性pH。此参考文献讨论了油包水型乳剂,其中甲硝唑和缓冲盐溶解或悬浮在油相组分中。
全文结合于此作为参考的美国专利U.S.Patent No.5,993,846(“Friedman等”),公开了一种用于例如阴道粘膜的粘膜表面的乳剂。特别地,Friedman公开了有增进的生物粘附性质的含药的水包脂质型乳剂。
全文结合于此作为参考的美国专利U.S.Patent No.6,191,105(“Ekwuribe等”),公开了自由型和/或共轭稳定化的治疗剂的微乳液剂。微乳剂包含油包水乳剂。Ekwuribe公开,可以根据鼻粘膜和眼对所给药物的耐受性,总体上调节乳剂的pH。Ekwuribe还讨论了所公开制剂的阴道给药。
全文结合于此作为参考的美国专利U.S.Patent No.6,294,550(“Place等”),公开了一种治疗女性性机能障碍的常规药物输送形式。此参考文献讨论了阴道给药的油包水乳剂。
然而,本文记载的药物输送系统的广泛使用受到以下因素的限制:(1)已知系统需要毒性量的佐剂或抑制剂;(2)不能得到适宜的低分子量治疗剂;(3)已知系统显示差的稳定性和不充分的保存期;(4)已知系统难于制备;(5)已知系统不能保护活性剂;(6)已知系统会有害地改变活性剂;(7)已知系统不能允许或促进活性剂的吸收;和/或(8)已知系统不能在充分延长的期间内释放活性剂。
相应地,现在提出的发明一方面提供一种pH基本为中性的阴道药物释放系统,其中包含pH基本为中性的乳剂,乳剂中有具有两相的药球,内相为含有一或多种治疗性活性药物的酸性缓冲的水溶相,外相为水不溶相或膜。本阴道药物释放系统的优点在于它为在阴道腔内释放治疗性活性药物提供了一种改进方式,其延长的释放周期长达168小时。相应地,药物释放系统优化了药物释放效率、药物治疗效果和治疗性活性药物产生的治愈率。本系统可以采用能方便地引入阴道腔内而不易从此体腔渗出的多相液体或半固体的形式。另一个优点是能缩短活性剂的治疗周期。
从说明书和权利要求书可以清楚地展示本发明的这些和其他方面。
发明概述
本发明的主题涉及一种由pH基本为中性的乳剂构成的pH基本为中性的阴道药物释放系统,其中的乳剂有具有两相的药球,以及制备和使用此阴道药物释放系统的方法。
更特别地,本发明的主题涉及一种pH基本为中性的阴道药物释放系统,其含有:
一种pH基本为中性的乳剂,它有具有两相的药球,内相为水溶相,外相为水不溶相或膜;
所述的内部水溶相包含含有一或多种治疗活性药物的酸性缓冲相,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的一或多种所述治疗活性药物;
其中酸性缓冲相为等渗、高渗或低渗。
本发明主题的另一实例是pH基本为中性的阴道药物释放系统,其中包含:
一种pH基本为中性的乳剂,它有具有两相的药球,内相为水溶相,外相为水不溶相或膜;
所述的内部水溶相包含含有一或多种微粉化的治疗活性药物的酸性缓冲相,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的一或多种所述微粉化的治疗活性药物;
其中酸性缓冲相为等渗、高渗或低渗;并且
其中微粉化的治疗活性药物具有在0.1微米至小于60.0微米范围内的颗粒大小,
其中酸性缓冲相使治疗活性药物的效果最大化;并且
其中酸性缓冲相的量足以中止阴道粘膜的炎症和瘙痒症状。
本发明主题的另一实例是pH基本为中性的阴道药物释放系统,其中包含:
一种pH基本为中性的乳剂,它有具有两相的药球:内相为水溶相,外相为水不溶相或膜;
所述的内部水溶相包含其本身pH约为2.0至约6.0的酸性缓冲相和治疗活性药物,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的治疗活性药物。
本发明主题的另一实例是治疗阴道疾病的方法,包括:给病人施用pH基本为中性的阴道药物释放系统,其中包含:
一种pH基本为中性的乳剂,它有具有两相的药球:内相为水溶相,外相为水不溶相或膜;
所述的内部水溶相包含含有一或多种治疗活性药物的酸性缓冲相,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的一或多种所述的治疗活性药物;
其中酸性缓冲相为等渗、高渗或低渗;并且
其中的治疗活性药物具有在0.1微米至小于60.0微米范围内的颗粒大小。对发明的详细描述
在此处用于描述有药球的乳剂,术语“药球”指用高剪切均化作用制备的圆形药球。另外,此处描述的药球有两相:内部包含酸性缓冲相的水溶相和外部的水不溶相或膜。
本发明的药物释放系统为“pH基本中性”,即整体上pH基本是中性,因为这些药物释放系统的水相不连续,所以不能测定其pH。因此,在完整的情况下,这些药物释放系统不显示pH值。只有构成即刻药物释放系统的药球的缓冲内相有非中性(酸性)的可测定的pH值。
关于本文的药球,术语“平均直径”是用粒径分析器-例如使用可以从Micromeritics(Norcross,Ga.)市售得到的SediGraph5100-得到的值。另外,可以通过测定用光学显微镜得到的照片中的至少100个药球的直径确定平均直径。
关于本文记载的乳剂的连续相、相间的组分或悬浮介质所用的术语“油”,是指这些介质具有疏水性因而不能与亲水相混溶。此术语不意味这些相必须由油组成或包括油。
此处使用的术语“稳定”或“稳定化的”指形成的药球在储藏过程中或在阴道给药时基本上能抵抗不希望的降解。
术语“生物相容的”指当单独或与pH控制剂配合引入病人组织中时,脂质体或聚合物不产生任何程度不能接受的毒性,包括变应原性反应和病态。优选地,脂质体或聚合物是惰性的。
此处使用的术语“微粉化的”指在约0.1微米至小于60.0微米的粒径范围。微粉化的治疗活性药物促进阴道释放系统的效能,因为它们接近包裹微粉化颗粒的药球载体的最优体积。
本发明的主题为阴道释放系统。此系统的特点是它们在延长的时间周期内以改进的方式向特定位置-阴道腔释放治疗活性药物,使药物治疗效果及药物释放效能达到最大的能力。此系统能生物粘附在上皮组织,并由至少两相构成。在阴道腔内,此系统在延长的停留时间里保持其完整性并显示物理稳定性。
如上所述,阴道腔产生有益于细菌、真菌、酵母和微生物生长的水性环境。现有技术的系统由于它们的水可混合性、缺乏生物粘附性或在37℃的阴道环境内缺乏物理稳定性而不能使治疗这些状况的效果最优化。此处定义的“阴道腔”不仅包括阴道,还包括任何另外的临近组织或表面。这些临近的组织或表面包括女性泌尿生殖道的任何部分,例如尿道口、子宫颈、子宫、外阴、输卵管、膀胱、结肠、肛门、直肠、卵巢、输尿管和输卵管。“释放系统”是为安全方便地释放精确剂量的所述治疗活性药物,而对治疗活性药物起溶解、悬浮、增稠、稀释、乳化、稳定、防腐、保护、着色、调味和风味作用使其制成可接受的和有效的制剂的非活性组分的组合。
本发明的阴道药物释放系统适于向阴道内缓和地释放治疗活性药物。这些阴道药物释放系统包含pH基本为中性的乳剂,它含有明确限定了外部水不溶相或膜和内部水溶性相的药球,内部的水溶相包含含有治疗活性药物的酸性缓冲相,其中的酸性缓冲相包含独立的所述治疗活性药物或它与另外的缓冲剂的结合。
典型地,本发明使用的药球有约0.1微米-约100微米的直径。在一优选实施例中,药球有约0.1微米至约60微米的粒径。在一特别优选的实施例中,药球有约0.5微米至约55微米的粒径。
本发明药球的外部由生物相容性的脂质体或聚合物材料构成,其中特别优选生物相容性脂质体。对于生物相容性脂质类材料,优选双亲性或疏水性组合物。双亲性组合物指既有亲脂性(疏水性)又有亲水性的物质的任何组合物。
天然和合成的磷脂是在制备本发明所用的药球的外表时作为乳化剂的脂质的例子。它们含有亲水性的带电荷的磷酸“端部”基团,连接到疏水性的长的碳氢尾上。此结构允许磷脂形成单一的双分子层(单层)排列,其中所有水不溶性碳氢尾相互接触,使高电荷的磷酸酯头部区域自由地与极性的水环境接触。可以理解的是能形成一系列同心的双分子层,即寡层和多层,这些排列也在本发明要求的范围之内。特别地,磷脂和磷脂的酯增加本发明的乳剂的稳定性。当使用主动治疗性活性药物时这点有特别的重要性。
制备本发明药球的壁最有用的稳定化化合物一般是有疏水/亲水特点使其能在水性介质存在下形成双层结构的化合物。因此,水、盐水或一些其他水性介质,以下通常称为稀释剂,可以形成本发明药球的外表,在此处这些形成双层的化合物作为稳定化化合物。
本发明优选的有用的双亲性的或疏水性的材料选自矿物油、脂质材料、中性脂肪、脂肪酸、脂肪酸酯、植物油、维生素油(vitamin oils)、果实的油、鱼油、来源于植物或动物的任何其它的油及其组合。根据本发明主题特别优选的脂质是磷脂。
本发明产生的药球的稳定性可以归因于由高剪切均化方法得到的药球所显示的非牛顿物理性质。高剪切均化方法的其它显著的特点是高的表面自由能和药球间的亲合力。
根据本发明的主题,在制备的药球中不必使用辅助的稳定化添加剂,即使这是可以选择的,并且这些辅助的稳定化剂是本领域普通技术人员已知的。
作为制备本发明药球的稳定化化合物的生物相容性聚合物可以是天然、半合成或合成的。
此处使用的术语聚合物指包含2个或多个重复的单节单位的化合物,优选有10或更多的重复单节单元。
此处使用的术语半合成聚合物指在一些方面经过化学修饰的天然聚合物。适用于本发明的示例性的天然聚合物包括天然产生的多糖。这些多糖包括例如阿拉伯糖、果糖、脱氧半乳聚糖、半乳聚糖、聚半乳糖醛酸、葡聚糖、甘露聚糖、木聚糖(例如菊粉)、果聚糖、岩藻依聚糖(fucoidan)、角叉菜胶、半乳卡洛糖、果胶酸、果胶、直链淀粉、出芽短梗霉聚糖(普鲁兰)、糖原、支链淀粉、纤维素、右旋糖酐、石脐素、壳多糖、琼脂糖、角质素(keratan)、软骨素(chondroitan)、皮肤素(dermatan)、透明质酸、海藻酸、黄原胶、淀粉,和各种其它天然均聚物或杂聚物,例如含有一或多个以下醛糖、酮糖、酸或胺的化合物:赤藓糖、苏阿糖、核糖、阿拉伯糖、木糖、来苏糖、阿洛糖、阿卓糖、葡萄糖、甘露糖、古洛糖、艾杜糖、半乳糖、塔罗糖、赤藓酮糖、核酮糖、木酮糖、阿洛酮糖、果糖、山梨糖、塔格糖、甘露糖醇、山梨糖醇、乳糖、蔗糖、海藻糖、麦芽糖、纤维二糖、甘氨酸、丝氨酸、苏氨酸、半胱氨酸、酪氨酸、天冬酰胺、谷氨酸盐、天门冬氨酸、谷氨酸、赖氨酸、精氨酸、组氨酸、葡糖醛酸、葡糖酸、葡糖二酸、半乳糖醛酸、甘露糖醛酸、葡糖胺、半乳糖胺、神经氨酸及其天然存在的衍生物。
适用于本发明的示例性的半合成聚合物包括羧甲基纤维素、羟甲基纤维素、羟丙甲基纤维素、甲基纤维素和甲氧基纤维素。
适用于本发明的示例性的合成聚合物包括聚乙烯(例如聚乙二醇、聚氧乙烯和聚乙烯对苯二酸酯)、聚丙烯(例如聚丙二醇)、聚氨基甲酸酯(例如聚乙烯醇(PVA)、聚氯乙烯和聚乙烯吡咯烷酮)、包括尼龙的聚酰胺、聚苯乙烯、聚合乳酸、氟化碳氢化合物、氟化碳(例如聚四氟乙烯)、聚甲基异丁烯酸酯及其衍生物。
可以用于制备本发明药球的外相或膜的另外的脂质或油包括但不限于:脂肪酸;溶血脂质(lysolipid);有饱和及不饱和脂质的卵磷脂,包括二油酰基卵磷脂、二豆蔻酰基卵磷脂、二-十五酰基卵磷脂、二月桂酰基卵磷脂、二棕榈酰基卵磷脂(DPPC)、二硬脂酰基卵磷脂(DSPC);磷脂酰乙醇胺,例如二油酰基磷脂酰乙醇胺和二棕榈酰基磷脂酰乙醇胺(DPPE);磷脂酰丝氨酸;磷脂酰甘油;磷脂酰肌醇;鞘脂类,例如神经鞘磷脂;糖脂(glycolipids),例如神经节苷脂GM1和GM2、葡萄糖脂(glucolipids);硫脂类;糖鞘脂(glycosphingolipids);磷脂酸,例如二棕榈酰基磷脂酸(DPPA);DHA;ω-3油;ω-6油;低芥子酸菜籽油;橘油;氢化植物油;矿物油;玉米油;棉籽油;花生油;芝麻油;大豆油;棕榈油;硬脂酸;花生四烯酸;油酸;含有聚合物例如聚乙烯醇的脂质,即PEG-基化脂质、壳多糖、透明质酸或聚乙烯吡咯烷酮;有磺化单-、二-、寡-或多糖的脂质;胆固醇、胆固醇硫酸酯和胆固醇偏琥珀酸酯(cholesterol hemisuccinate);维生素E偏琥珀酸酯;有连接醚和酯的脂肪酸的脂质;聚合脂质(本领域已知的多种);二乙酰磷酸酯;三十二烷磷酸酯;硬脂酰胺;心磷脂;有长度为6-8碳的短链脂肪酸的磷脂;有不对称酰基链的合成磷脂(例如,有一个6碳的酰基链和另一个12碳的酰基链);神经酰胺;包括非离子表面活性剂微囊(niosomes)的非离子脂质体,例如聚氧乙烯脂肪酸酯、聚氧乙烯脂肪醇、聚氧乙烯脂肪醇酯、聚氧乙基化脱水山梨醇脂肪酸酯、甘油基聚乙二醇羟基硬脂酸酯、甘油基聚乙二醇蓖麻油酸酯、乙氧基化豆甾醇、乙氧基化海狸油,聚氧乙烯-聚氧丙烯聚合物和聚氧乙烯脂肪酸硬脂酸酯;甾醇脂肪酸酯,包括胆固醇硫酸酯、胆固醇丁酸酯、胆固醇异丁酸酯、胆固醇棕榈酸酯、胆固醇硬脂酸酯、羊毛甾醇醋酸酯、麦角甾醇棕榈酸酯,和植物甾醇正丁酸酯;糖酸甾醇酯,包括胆固醇葡萄糖醛酸化物,羊毛甾醇葡萄糖醛酸化物,7-脱氢胆甾醇葡萄糖醛酸化物,麦角甾醇葡萄糖醛酸化物,胆固醇葡萄糖酸酯,羊毛甾醇葡萄糖酸酯,和麦角甾醇葡萄糖酸酯;糖酸和醇的酯,包括月桂基葡萄糖醛酸化物,硬脂酰葡萄糖醛酸化物,肉豆蔻酰葡萄糖醛酸化物,月桂基葡萄糖酸酯,肉豆蔻酰葡萄糖酸酯,和硬脂酰葡萄糖酸酯;糖和脂肪酸的酯,包括蔗糖月桂酸酯、果糖月桂酸酯、蔗糖棕榈酸酯、蔗糖硬脂酸酯、葡萄糖醛酸、葡萄糖酸、糖质酸(saccharic acid)和多糖醛酸;皂甙,包括萨洒皂角苷配基(sarsasapogenin)、菝葜配基(smilagenin)、常春藤皂甙元、齐墩果酸和毛地黄毒苷配基;甘油,和包括以下种的甘油酯:甘油二月桂酸酯、甘油三月桂酸酯、甘油二棕榈酸酯、甘油三棕榈酸酯、甘油二硬脂酸酯、甘油三硬脂酸酯、甘油二肉豆蔻酸酯,和甘油三肉豆蔻酸酯;长链醇,包括正癸基醇、月桂醇、肉豆蔻醇、鲸蜡醇和正十八烷醇;6-(5-胆甾烯-3β-基氧)-1-硫代-β-D-吡喃半乳糖甙;双半乳糖甘油二酯;6-(5-胆甾烯-3β-基氧)己基-6-氨基-6-去氧-1-硫代-β-D-吡喃半乳糖甙;6-(5-胆甾烯-3β-基氧)己基-6-氨基-6-去氧-1-硫代-α-D-吡喃甘露糖甙;12-(((7′-二乙基氨基香豆素-3-基)羰基)甲氨基)-硬脂酸;N-12-(((7′-二甲基氨基香豆素-3-基)羰基)甲氨基)十八烷酰基-2-氨基棕榈酸;胆甾醇基(4’-三甲基氨基)丁酸酯;N-琥珀酰二油酰磷脂酰基乙醇胺;1,2-二油酰基-sn-甘油;1,2-二棕榈酰基-sn-3-琥珀酰基甘油;1,3-二棕榈酰基-2-琥珀酰甘油;1-十六烷基-2-棕榈酰基-甘油磷酸乙醇胺(glycerophosphoe thanolamine)和棕榈酰基高半胱氨酸和/或它们的组合。
本发明pH基本为中性的阴道药物释放系统还可以含有其它赋形剂,选自:润滑剂、清洗剂、除臭剂、湿润剂、软化剂、增塑剂、粘合剂、乳化剂、稳定剂、溶剂、生物可吸收材料、增溶剂、抗微生物防腐剂、稀释剂、助流剂、悬浮剂、延迟释放剂(extended-release agents)、包衣剂、吸附剂、崩解剂、螫合剂,及其混合物和组合。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性润滑剂选自:硬脂酸钙、低芥子酸菜籽油、甘油基棕榈酸硬脂酸酯、氢化植物油、氧化镁、矿物油、泊咯沙姆、聚乙二醇、聚乙烯醇、苯甲酸钠、月桂基硫酸钠、硬脂酰基富马酸钠、硬脂酸、灭菌的玉米淀粉、滑石粉、硬脂酸锌及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性湿润剂选自:甘油、丙二醇、山梨醇、甘油三乙酸酯及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性软化剂选自: 鲸蜡硬脂醇、羊毛脂、矿物油、凡士林、十六烷基酯蜡、胆固醇、甘油、甘油基单硬脂酸酯、异丙基肉豆蔻酸酯、异丙基棕榈酸酯、卵磷脂及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性增塑剂选自:羊毛脂、矿物油、凡士林、苯甲酸苄酯、三氯叔丁醇、二乙基邻苯二甲酸酯、甘油、聚乙二醇、山梨醇、甘油三乙酸酯、二乙基癸二酸酯、三乙基柠檬酸酯、巴豆酸、丙二醇、丁基邻苯二甲酸酯、二丁基癸二酸酯、海狸油及其混合物。显然,增塑剂的性质可以是疏水性和亲水性的。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性粘合剂选自:阿拉伯胶、海藻酸、羧甲基纤维素、羟乙基纤维素、羟丙基纤维素、糊精、乙基纤维素、明胶、液体葡萄糖、氢化植物油、羟丙基甲基纤维素、硅酸铝镁、麦芽糖糊精、甲基纤维素、聚氧乙烯、聚甲基丙烯酸酯、聚维酮、藻酸钠、淀粉、玉米醇溶蛋白、丙烯酸和甲基丙烯酸的共聚物、药用釉(pharmaceutical glaze),树胶,例如瓜尔胶,和乳的衍生物,例如乳清,及淀粉,及本领域技术人员已知的其他常规粘合剂。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性稳定化剂选自:阿拉伯胶、白蛋白、聚乙烯醇、海藻酸、膨润土、羧甲基纤维素、羟丙基纤维素、硅胶、环糊精、甘油基单硬脂酸酯、羟丙基甲基纤维素、硅酸铝镁、丙二醇、丙二醇藻酸酯、藻酸钠、蜡、黄原胶及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性溶剂选自:乙醇、苯甲酸苄酯、玉米油、棉籽油、二乙基邻苯二甲酸酯、乙基油酸酯、甘油、葡萄糖糠醛(glycofurol)、异丙醇、异丙基肉豆蔻酸酯、中链甘油三酯、矿物油、花生油、聚乙二醇、碳酸异丙烯酯、丙二醇、芝麻油、豆油、甘油三乙酸酯及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性增溶剂选自:氯化苯甲烃铵、海狸油、环糊精、聚氧乙烯醚、甘油基单硬脂酸酯、卵磷脂、泊咯沙姆、聚山梨醇酯、聚氧乙烯硬脂酸酯、脱水山梨醇酯、硬脂酸及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性抗微生物防腐剂选自:苯甲酸、EDTA、酚酸、山梨酸、苯甲醇、异丙醇、氯化苯甲乙氧铵、溴硝丙二醇、尼泊金丁酯、溴化十六烷基三甲铵、氯己定、三氯叔丁醇、氯甲酚、甲酚、羟苯乙酯、甘油、亚胺脲(imidurea)、尼泊金甲酯、苯酚、苯氧基乙醇、乙酸苯汞、硼酸苯汞、硝酸苯汞、山梨酸钾、丙二醇、尼泊金丙酯、苯甲酸钠、丙酸钠、山梨酸、乙基汞硫代水杨酸钠及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性稀释剂选自:磷酸钙、硫酸钙、羧甲基纤维素钙、纤维素、醋酸纤维素、葡萄糖结合剂(dextrates)、糊精、葡萄糖、果糖、甘油基硬脂酸棕榈酸酯(glycerylpalmitostearate)、高岭土、乳糖醇、乳糖、碳酸镁、氧化镁、麦芽糖醇、麦芽糖糊精、麦芽糖、微晶纤维素、聚甲基丙烯酸酯、粉状纤维素、预胶化淀粉、硅酸化微晶纤维素、氯化钠、山梨醇、淀粉、蔗糖、糖、滑石、氢化植物油及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性助流剂选自:麦芽糖醇、聚合葡萄糖、蔗糖及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性悬浮剂选自:海藻酸、膨润土、卡波姆(carbomer)、羧甲基纤维素、羟乙基纤维素、羟丙基纤维素、微晶纤维素、糊精、明胶、瓜尔胶、黄原胶、高岭土、硅酸铝镁、麦芽糖醇、甲基纤维素、聚山梨酯(polysorbate)、聚维酮、藻酸丙二酯、藻酸钠、脱水山梨醇酯、黄芪胶及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性延迟释放剂选自:角叉菜胶、醋酸纤维素、甘油基单硬脂酸酯、玉米醇溶蛋白及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性崩解剂选自:海藻酸、羧甲基纤维素钠、羟丙基纤维素、微晶纤维素、硅胶、交联羧甲基纤维素钠(croscarmellose sodium)、交联聚维酮(crospovidone)、硅酸铝镁、甲基纤维素、波拉克林(polacrilin)、聚维酮、藻酸钠、羟乙酸淀粉钠、淀粉及其混合物。
根据本发明主题,可以作为其他赋形剂的非限定性的示例性螯合剂选自:EDTA、苹果酸、麦芽酚及其混合物。
本发明主题的一个重要的特色是当药物释放系统作为一个整体基本是中性时,内部的水溶相由酸性缓冲相构成,酸性缓冲相含有独立的或与附加的缓冲剂结合的一或多种治疗活性药物。在内相建立酸性pH缓冲剂已显示能增强其中结合的抗真菌剂和其他抗菌剂的功效。此增强的功效可能是缓冲组分扩散在阴道腔中并将阴道分泌物的pH值缓冲调节到大约4.5的结果。在阴道穹隆的生理最佳pH,此pH对通常的病原体是有害的,例如属于真菌病原体的假丝酵母属,和属于细菌病原体的肠球菌属(Enterococci)。另外,因为4.5或在此值附近的pH对于阴道环境是最佳的,此pH也能帮助消除炎症、瘙痒和见于其他急性感染性疾病中的不适。结果,本发明的组合物能优化对这些病原体的治疗效果。
正常地,对阴道穹隆施以酸性组合物将刺激阴道腔引起严重的不适。相应地,本发明主题确定为pH基本为中性的阴道药物释放系统。只有构成此释放系统的药球的缓冲内相是酸性的。因为将缓冲系统螯合在药球壁内,药球的整个酸性缓冲内相将不刺激阴道腔。因此,酸性缓冲液不直接与阴道内壁接触。如果试图测定乳剂的pH值,内相开始释放之前不会产生pH值读数,所以形成一个pH基本为中性的药物释放系统。
本发明pH基本为中性的药物释放系统的另一优点是内部酸性缓冲相的酸性缓冲组分慢慢从药球的内相释放,即释放周期长达约168小时。这避免了对周围组织的突然的酸性刺激。这对于高度炎症和感染的阴道腔具有特别的重要性。
相应地,药球的内部酸性缓冲相有正电荷,其本身pH小于6.0。在一个优选实施例中,酸性缓冲相本身pH为约2.5-约5.5。在一个特别优选的实施例中,酸性缓冲相本身的pH为约3.5-约5.0。
酸性缓冲相可以使用的优选的缓冲溶液由弱酸和此酸的盐或弱碱和此碱的盐构成。本发明可以使用的缓冲系统优选的非限制性例子选自:醋酸/醋酸钠或醋酸钾,氯化铵/氢氧化铵,苯甲酸/苯甲酸钠或苯甲酸钾,硼酸/硼酸钠,柠檬酸/磷酸氢二钠,柠檬酸/柠檬酸钠或柠檬酸钾,乳酸/乳酸钠或乳酸钾,钠或钾的一元或二元磷酸盐,邻苯二甲酸氢钾/氢氯酸,琥珀酸/琥珀酸钠或琥珀酸钾,和酒石酸/酒石酸钠或酒石酸钾。
另外,本发明的释放系统为治疗活性药物提供约0.1小时至约168小时的释放速率。在另一优选实施例中,本发明的释放系统为治疗活性药物提供约0.1小时至约72小时的释放速率。
本发明主题影响治疗活性药物释放速率的另一方面是在克分子渗透压浓度的宽范围内调整药球酸性缓冲相的渗透压的能力。相应地,药球的缓冲相可以为等渗、高渗或低渗。制备具有可变渗透压的药球的能力是使用本发明pH基本为中性的阴道药物释放系统的另一优势。
在一优选实施例中,药球的酸性缓冲相是等渗的。等渗的酸性缓冲相将有与生物组织相同的渗透压,等于300±10毫渗克分子(milliosmol)/升。等渗酸性缓冲相通过扩散从药球中释放治疗活性药物。相应地,有等渗酸性缓冲相的药球可以在一次用药后持续数天或数周提供治疗活性药物的缓慢的释放。
在另一优选实施例中,药球的酸性缓冲相是高渗的。高渗酸性缓冲相有高于生物组织的渗透压,即高于300±10毫渗克分子(milliosmol)/升。高渗酸性缓冲相通过药球的破裂从药球中释放治疗活性药物。相应地,治疗活性药物在给药后约5分钟至约60分钟内持续释放到作用部位。
还有另一优选实施例,药球的酸性缓冲相是低渗的。低渗酸性缓冲相有低于生物组织的渗透压,即低于300±10毫渗克分子(milliosmol)/升。低渗酸性缓冲相通过扩散和渗透从药球中释放治疗活性药物。相应地,在给药后治疗活性药物持续向作用部位释放至少约1小时。
相应地,在本发明主题的一个实施例中,酸性缓冲相有高于300±10毫渗克分子(milliosmol)/升的渗透压。在本发明主题的另一实施例中,酸性缓冲相有低于300±10毫渗克分子(milliosmol)/升的渗透压。本发明主题还有另一个实施例,酸性缓冲相有等于300±10毫渗克分子(milliosmol)/升的渗透压。
影响治疗活性药物释放速率的其它因素是各相中所含治疗活性药物的百分比、外膜的厚度、外相或膜中乳化剂的数量和性质、内相的pH、活性成分通过外相或膜的扩散性等。在阴道腔的生理环境中,表现出的全部化学和物理影响因素,包括分泌液、酶、pH、化学平衡、温度和身体运动产生的剪切力,影响系统破裂的速度。这些因素不以与已知系统相同的速度影响本系统的完整性。
本发明主题使用的治疗活性药物可以是任何被批准或已使用的用于处理、预防、治疗或减轻阴道、泌尿道、子宫或其它女性生殖器官的疾病或妊娠诱因、用于美容或化妆用途、用于诊断目的、用于全身药物治疗,或用于后代性别测定的药物。当通过释放到阴道表面的全部或部分区域而给药时,药剂必须有效。潜在的药剂由于获得政府批准或通常的使用而是众所周知的。在本发明的组合物中使用这些治疗活性药物将优化这些药物产生的治疗效果。
用于本药物释放系统的优选的治疗活性药物选自:抗真菌剂、抗细菌剂、抗微生物剂、抗病毒剂、杀精子剂、激素药物、抗阴道滴虫药、抗原虫药、抗支原体药物、抗逆转录病毒剂、核苷类似物、逆转录酶抑制剂、蛋白酶抑制剂、避孕药、磺胺药类(sulfadrugs)、磺胺类药物、砜类药物、保健剂、前生物剂、疫苗、抗体、肽制剂、蛋白质制剂、多糖药物、核酸、质粒、脂质体、碳氢聚合物、转基因细菌、酵母、化疗药、甾体药物、生长促进剂、性欲增强剂、雄激素物质、壳多糖衍生物、环境改善剂例如pH调节剂,及其混合物或组合。
在一优选实施例中,治疗活性药物是抗真菌剂。在一特别优选的实施例中,治疗活性药物是选自以下种类的抗真菌剂:硝酸布康唑、克霉唑、硝酸酮康唑、咪康唑(miconizole)、多烯抗真菌剂、制霉菌素、两性霉素B、匹马菌素、硝酸奥昔康唑、硝酸特康唑、噻康唑、氟三唑(flutrimazole)、吲康唑(intraconizole)、丙烯胺、特本萘芬(terbenafine)、布替那芬、阿莫罗芬、萘替芬、葡康唑(gluconazole)、唑类、益康唑、voriconizole、氟康唑、泼洒康唑(posaconazole)、硫康唑、diction双苯并咪唑(diction bisbenzimidazoles)、葡聚糖合成抑制剂、echinacandins、anidulafungin、caspofungin、micafugin、抗结核药、间苯基砜(diaphenylsulfone)、环匹罗司、卤普罗近、tolnatane、十一碳烯酸酯及其混合物和组合。
在另一优选实施例中,治疗活性药物是抗菌剂。在一特别优选的实施例中,治疗活性药物是选自如下种的抗菌剂:克林霉素、磺胺类药物、红霉素、克拉霉素、阿齐霉素(azythromycin)、四环素、多沙霉素(doxacline)、甲硝唑、大环内酯类、酮大环内酯类(ketolide)、喹诺酮、头孢菌素、碳青霉烯、青霉素、庆大霉素、爪蟾抗菌肽(magaininpeptides)、dalbavancin、雷莫拉宁、iseganan、头孢西丁、头孢曲松、三氯醋酸及其混合物和组合。
还有另一优选实施例,治疗活性药物是抗病毒剂。在一特别优选的实施例中,治疗活性药物是选自如下种的抗病毒剂:喷昔洛韦、阿昔洛韦、更昔洛韦、膦甲酸盐、缬昔洛韦、pleconaril及其混合物和组合。
还有另一优选实施例,治疗活性药物是杀精子剂。在一特别优选的实施例中,治疗活性药物是杀精子剂壬苯醇醚-9(nonoxyl-9)。
在另一优选实施例中,治疗活性药物是生长促进剂。在一特别优选的实施例中,治疗活性药物是选自细胞因子构成的组的生长促进剂。
还有另一优选实施例,治疗活性药物是表面活性药物。在一特别优选的实施例中,表面活性药物是磷酸克林霉素。
还有另一优选实施例,治疗活性药物是雄激素物质。在一特别优选的实施例中,雄激素物质选自达那唑、睾酮及其混合物和组合。
本发明药物释放系统的内部水溶相的治疗活性药物是微粉化物质,其颗粒大小在约0.1微米-小于60微米范围内。在一优选实施例中,治疗活性药物的颗粒大小为约0.1微米-约15微米。相应地,在本发明的药物释放系统中可以使用可溶性和微溶性药物。
对本释放系统显示的微溶性治疗活性药物-例如布他康唑(butaconazole)、克霉唑和氟曲马唑-效能上增强的可能的解释被认为是,与随着相对水不溶性药物粒径的降低,而显现溶解速率增加有关。认为内部水溶相中微粉化的治疗活性药物可以根据存在于内相之外和内相中的治疗活性药物数量之间平衡的改变迅速调整。快速溶解能够快速重建此平衡。不经过微粉化,必须经过一段时间重新建立平衡,在感染部位产生低水平量的可扩散的治疗活性药物。
在本发明主题的另一实施例中,外部水不溶相或膜在酸性缓冲相之外含有附加的治疗活性药物。在一个优选实施例中,将外相或膜中的附加的治疗活性药物微粉化,其颗粒大小为约0.5微米-小于60.0微米。在另一实施例中,外相或膜中附加的治疗活性药物不经过微粉化。还有另一实施例,外相或膜中的附加治疗活性药物是微粉化和不经过微粉化的。
在本发明主题的一个优选实施例中,酸性缓冲相中和酸性缓冲相之外的微粉化药物与未微粉化的药物的比例为约0.1至约1,000。
可以用常规的涂药器或其他敷层、喷雾器、泡沫器或气溶胶装置或给药技术领域普通技术人员已知的任何可能的装置将本发明药物释放系统用于阴道腔内。
或者,本系统在生理温度,约37℃是可变形的,它们不会像在先技术的系统那样失去其完整性。不同于已知系统,这些释放系统没有在置入阴道腔后从其中渗漏的特点。因为这些系统在延长的时间周期内破裂,它们的非水性成分以低于通常剂型的速率从阴道腔吸收或释放。
本发明主题的示例性的释放系统包括但不限于分散体、固体、悬浮液、软膏、泥敷剂(膏状物)、膏剂、粉末、药丸(ovules)、栓剂、泡沫剂、敷料、霜剂、溶液、液体、冻胶、喷雾剂、凝胶剂、片剂(包括速溶片剂)、棉塞、海绵剂、药枕、膨胀剂(puffs)和贴剂。
本发明主题还涉及治疗阴道疾病的方法,包括给病人使用本发明所述的pH基本为中性的阴道药物释放系统。特别地,阴道疾病包括以下引起的感染:假丝酵母、肠球菌、链球菌、葡萄球菌、尿路病原体、大肠杆菌(E.coli)、克雷白氏杆菌属、梭菌、动弯杆菌(Mobiluncus species)、加德纳氏菌属(Gardnerella)、普雷沃氏菌(Prevotella species)、假单孢属细菌、原虫、支原体属(mycoplasm)、衣菌属(Chlamydia)、HIV、HPV、疱疹(herpes)、非特异性阴道炎(nonspecific vaginitis)、淋病奈瑟氏球菌(N.gonorrhoeae)、阴道毛滴虫、砂眼衣原体,及其混合和组合。
根据本发明主题可以治疗的另外的阴道疾病包括所有形式的子宫内膜异位、宫外子宫内膜异位、子宫内膜炎、癌症、卵巢囊肿、输卵管炎、子宫纤维瘤、其他生殖器病毒性疾病、生殖器疣及其混合性疾病和组合。
可以用各种为剪切混合提供充分的高剪切力的装置制备本发明的药球。市场上可以得到多种这些装置,包括微流体化器-例如生物技术发展公司制造的“French”型压片机,或提供足够高剪切力的其他装置。
Micro Vesicular Systems,Inc.,Vineland,N.J.开发了一种制备本发明药球特别有用的装置,在美国专利U.S.Patent No.4,895,452中有进一步描述,将其全文结合于此作为参考。
此装置有一个基本为圆筒形的混合室,此混合室有至少一个正切向定位的进料口。一或多个入口将水不溶相导向储存室,至少一个其他的入口将水溶相连接到储存室。
通过泵-例如容积泵将不同相送入圆筒形混合室中,并以在混合室中形成湍流的方式交汇。通过轴向固定的排放孔将药球排出。
在水溶相混合室中,生物活性治疗剂与稀释剂混合。在水不溶相混合室中加入起稳定作用的化合物。然后在筒形混合室中加入表面活性剂,按约30,000转/分钟(“rpm”)的转速混合两相。
本发明使用的一些非限制性的表面活性剂的例子包括琥珀辛酯钠、月桂基硫酸钠、溴化十六烷基三甲铵、聚氧乙烯脂肪酸酯和脱水山梨醇酯。
本领域普通技术人员不经过过度的试验可以改变高剪切均化的转速产生基本相同的发明而不超出本发明公开的范围。而且,当本发明公开的内容与现有技术已知的信息结合时,参考本发明公开的内容,本领域技术人员将很清楚制备这些pH基本为中性的药物释放系统的制备方法。本发明的理论
不将本发明的理论限制为任何特定的理论,为有本发明药球的乳剂的新机理建立了一些可能的解释。
根据脉冲乳剂现象理论(“PEP”),治疗活性药物从药球的酸性缓冲相中的释放依赖于环境pH或周围环境中存在的酶的种类。根据pH依赖性模型,药球在适合的环境pH条件下停留于阴道粘膜内层并释放生物活性治疗剂。
根据酶依赖性模型,生物学存在的酶可以触发或阻止停留/释放过程。例如,阴道腔中的脂肪酶可以触发将治疗剂释放到阴道腔而通过粘膜吸收的停留/释放过程。
粘膜停留囊理论假设显著的吸收仅发生在粘膜上皮。可能药球仅与粘膜基层或粘液本身接触。停留/释放过程仅发生在粘膜表面。通过停留/释放过程,螯合在小囊中的生物活性药物通过粘膜基底膜扩散,并进入血液而分配。
对停留/释放过程的另一个解释是药球与粘膜之间的范德华(VanderWaal)相互作用力。范德华力是一个分子受另一个分子的作用而产生的暂时的偶极。此物理吸引力与代替汽车窗附着贴的附着于玻璃的塑料贴采用的“静态附着”相似。范德华力可以触发停留和随后的释放。
本领域的普通技术人员将认识到本发明的特定的理论不局限于上述理论的任何一种,或者可以是上述理论的组合,或包括尚未阐明的理论,并绝不局限于实施本文公开的发明的能力。
下述实例是对本发明优选实施例的说明,并不能解释为对本发明的限制。所有聚合分子量是平均分子重量。除非另外说明,所有百分比基于最终释放系统或所制备制剂的重量百分数,其总和等于重量的100%。实施例
甲硝唑和克林霉素示例性说明在设计有效的阴道药物释放系统方面遇到的问题。可以用任何数量的技术方便地改变甲硝唑和克林霉素的药物性质,但它们的物理化学性质限制阴道释放系统的设计。
用本发明pH基本为中性的阴道药物释放系统制备以下实例。实施例I
表I
组分 | 数量%w/w |
纯化水 | 24.676 |
甘油 | 47.250 |
冰醋酸 | 0.225 |
醋酸钠 | 0.200 |
氯化钠 | 0.750 |
尼泊金甲酯 | 0.090 |
尼泊金丙酯 | 0.035 |
尼泊金丁酯 | 0.024 |
蔗糖 | 8.000 |
甲硝唑 | 0.750 |
矿物油 | 13.000 |
聚乙二醇(30)二聚羟基硬脂酸酯 | 5.000 |
可以用各种本领域已知的为剪切混合提供充分的高剪切力的装置制备本发明的药物释放系统使用的药球。Micro VesicularSystems,Inc.,Vineland,N.J.开发了一种特别有用的装置,在美国专利U.S.Patent No.4,895,452中有进一步描述。根据最终需要的产品确定采用的温度。在制备药球前测定药球的内部水溶解相的pH以保证pH在前述临界pH范围内。
用以下方法制备这些实施例中记载的制剂:
用纯化水将甲硝唑和内部水溶相另外的成分混合。在第二容器中将外部水不溶相或膜中的成分混合。将内部水溶相缓慢加入外部水不溶相或膜中,同时用叶片-圆盘搅拌器将两相混合直至内相完全加入到外相中并得到所需的粘度。根据最终所需的产品确定混合速度。实施例II
可以用例I的方法制备具有下述配方的磷酸克林霉素释放系统。
表II
组分 | 数量%w/w |
纯化水 | 24.676 |
甘油 | 45.200 |
冰醋酸 | 0.225 |
醋酸钠 | 0.200 |
氯化钠 | 0.750 |
尼泊金甲酯 | 0.090 |
尼泊金丙酯 | 0.035 |
尼泊金丁酯 | 0.024 |
蔗糖 | 8.000 |
磷酸克林霉素 | 2.800 |
矿物油 | 12.000 |
聚乙二醇(30)二聚羟基硬脂酸酯 | 6.000 |
如上描述了本发明,显然同一发明可以有多种方式的变化。这些变化不应认为偏离了本发明的实质范围,所有这些改变应包括在以下权利要求的范围之内。
Claims (57)
1.一种pH基本为中性的阴道药物释放系统,其中包含:
pH基本为中性的乳剂,它有具有两相的药球:内部的水溶相,和外部的水不溶相或膜;
所述的内部水溶相包含含有一或多种治疗活性药物的酸性缓冲相,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的一或多种所述的治疗活性药物;
其中酸性缓冲相为等渗、高渗或低渗。
2.权利要求1所述的组合物,其中的治疗活性药物是微粉化的,并具有在约0.1微米至小于60微米范围内的粒径。
3.权利要求2所述的组合物,其中的治疗活性药物具有在约0.1微米至小于约15微米范围内的粒径。
4.权利要求1所述的组合物,其中的药球具有在约0.1微米至约100微米范围内的粒径。
5.权利要求4所述的组合物,其中的药球具有在约0.1微米至约60微米范围内的粒径。
6.权利要求5所述的组合物,其中的药球具有在约0.5微米至约55微米范围内的粒径。
7.权利要求1所述的组合物,其中的酸性缓冲相其本身pH小于6.0。
8.权利要求7所述的组合物,其中的酸性缓冲相其本身pH为约2.5至约5.5。
9.权利要求8所述的组合物,其中的酸性缓冲相其本身pH为约3.5至约5.0。
10.权利要求1所述的组合物,其中的治疗活性药物选自:抗真菌剂、抗细菌剂、抗微生物剂、抗病毒剂、杀精子剂、激素药物、抗阴道滴虫药、抗原虫药、抗支原体药物、抗逆转录病毒剂、核苷类似物、逆转录酶抑制剂、蛋白酶抑制剂、避孕药、磺胺药类、磺胺类药物、砜类药物、保健剂、前生物剂、疫苗、抗体、肽制剂、蛋白质制剂、多糖药物、核酸、质粒、脂质体、碳氢聚合物、转基因细菌、酵母、化疗药、甾体药物、生长促进剂、性欲增强剂、雄激素物质、壳多糖衍生物、环境改善剂例如pH调节剂,及其混合物或组合。
11.权利要求10所述的组合物,其中的治疗活性药物是选自细胞因子构成的组的生长促进剂。
12.权利要求1所述的组合物,还含有赋形剂,选自:润滑剂、清洗剂、除臭剂、湿润剂、软化剂、增塑剂、粘合剂、乳化剂、稳定剂、溶剂、生物可吸收材料、增溶剂、抗微生物防腐剂、稀释剂、助流剂、悬浮剂、延迟释放剂、包衣剂、吸附剂、崩解剂、螫合剂,及其混合物和组合。
13.权利要求10所述的组合物,其中的治疗活性药物选自:硝酸布康唑、克霉唑、硝酸酮康唑、咪康唑、多烯抗真菌剂、制霉菌素、两性霉素B、匹马菌素、硝酸奥昔康唑、硝酸特康唑、噻康唑、氟三唑、吲康唑、丙烯胺、特本萘芬、布替那芬、阿莫罗芬、萘替芬、葡康唑、唑类、益康唑、voriconizole、氟康唑、泼洒康唑、硫康唑、dictionbisbenzimidazoles、葡聚糖合成抑制剂、echinacandins、anidulafungin、caspofungin、micafugin、抗结核药、间苯基砜、环匹罗司、卤普罗近、tolnatane、十一碳烯酸酯及其混合物和组合。
14.权利要求10所述的组合物,其中的治疗活性药物是选自以下种的抗菌剂:克林霉素、磺胺类药物、红霉素、克拉霉素、阿齐霉素、四环素、多沙霉素、甲硝唑、大环内酯类、酮大环内酯类、喹诺酮、头孢菌素、碳青霉烯、青霉素、庆大霉素、爪蟾抗菌肽、dalbavancin、雷莫拉宁、iseganan、头孢西丁、头孢曲松、三氯醋酸及其混合物和组合。
15.权利要求10所述的组合物,其中的治疗活性药物是选自以下种的抗病毒剂:喷昔洛韦、阿昔洛韦、更昔洛韦、膦甲酸盐、缬昔洛韦、pleconaril及其混合物和组合。
16.权利要求10所述的组合物,其中的治疗活性药物是杀精子剂壬苯醇醚-9。
17.权利要求10所述的组合物,其中的雄激素物质选自达那唑、睾酮及其混合物和组合。
18.权利要求1所述的组合物,其中的外部水不溶相或膜在酸性缓冲相外含有附加的治疗活性药物。
19.权利要求18所述的组合物,其中外相或膜中的附加的治疗活性药物是微粉化的,并具有在约0.5微米至小于60.0微米范围内的粒径。
20.权利要求18所述的组合物,其中外相或膜中的附加的治疗活性药物是未微粉化的。
21.权利要求18所述的组合物,其中外相或膜中的附加的治疗活性药物是微粉化和未微粉化的。
22.权利要求21所述的组合物,其中酸性缓冲相中和酸性缓冲相之外的微粉化药物与未微粉化的药物的比例为约0.1至约1,000;其中治疗活性药物的释放速率为约0.1小时至约168小时。
23.权利要求1所述的组合物,其中的酸性缓冲相具有高于300±10毫渗克分子/升的渗透压。
24.权利要求1所述的组合物,其中的酸性缓冲相具有低于300±10毫渗克分子/升的渗透压。
25.权利要求1所述的组合物,其中的酸性缓冲相具有等于300±10毫渗克分子/升的渗透压。
26.权利要求1所述的组合物,其中的治疗活性药物是表面活性药物。
27.权利要求26所述的组合物,其中的表面活性药物是磷酸克林霉素。
28.一种pH基本为中性的阴道药物释放系统,其中包含:
pH基本为中性的乳剂,它有具有两相的药球:内部的水溶相,和外部的水不溶相或膜;
所述的内部水溶相包含含有一或多种微粉化的治疗活性药物的酸性缓冲相,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的一或多种所述的微粉化的治疗活性药物;
其中酸性缓冲相为等渗、高渗或低渗;并且
其中微粉化的治疗活性药物具有在0.1微米至小于60.0微米范围内的粒径,
其中酸性缓冲相使治疗活性药物的效果最大化;并且
其中的酸性缓冲相的量足以中止阴道粘膜的炎症和瘙痒症状。
29.权利要求28所述的组合物,其中的酸性缓冲相带正电荷,其本身pH在约2.5-约5.0之间。
30.权利要求28所述的组合物,其中的治疗活性药物选自:抗真菌剂、抗细菌剂、抗微生物剂、抗病毒剂、杀精子剂、激素药物、抗阴道滴虫药、抗原虫药、抗支原体药物、抗逆转录病毒剂、核苷类似物、逆转录酶抑制剂、蛋白酶抑制剂、避孕药、磺胺药类、磺胺类药物、砜类药物、保健剂、前生物剂、疫苗、抗体、肽制剂、蛋白质制剂、多糖药物、核酸、质粒、脂质体、碳氢聚合物、转基因细菌、酵母、化疗药、甾体药物、生长促进剂、性欲增强剂、雄激素物质、壳多糖衍生物、环境改善剂例如pH调节剂,及其混合物或组合。
31.权利要求30所述的组合物,其中的治疗活性药物是选自细胞因子构成的组的生长促进剂。
32.权利要求28所述的组合物,还含有赋形剂,选自:润滑剂、清洗剂、除臭剂、湿润剂、软化剂、增塑剂、粘合剂、乳化剂、稳定剂、溶剂、生物可吸收材料、增溶剂、抗微生物防腐剂、稀释剂、助流剂、悬浮剂、延迟释放剂、包衣剂、吸附剂、崩解剂、螫合剂,及其混合物和组合。
33.权利要求30所述的组合物,其中的治疗活性药物是抗真菌剂,选自:硝酸布康唑、克霉唑、硝酸酮康唑、咪康唑、多烯抗真菌剂、制霉菌素、两性霉素B、匹马菌素、硝酸奥昔康唑、硝酸特康唑、噻康唑、氟三唑、吲康唑、丙烯胺、特本萘芬、布替那芬、阿莫罗芬、萘替芬、葡康唑、唑类、益康唑、voriconizole、氟康唑、泼洒康唑、硫康唑、dictionbisbenzimidazoles、葡聚糖合成抑制剂、echinacandins、anidulafungin、caspofungin、micafugin、抗结核药、间苯基砜、环匹罗司、卤普罗近、tolnatane、十一碳烯酸酯及其混合物和组合。
34.权利要求30所述的组合物,其中的治疗活性药物是选自以下种的抗菌剂:克林霉素、磺胺类药物、红霉素、克拉霉素、阿齐霉素、四环素、多沙霉素、甲硝唑、大环内酯类、酮大环内酯类、喹诺酮、头孢菌素、碳青霉烯、青霉素、庆大霉素、爪蟾抗菌肽、dalbavancin、雷莫拉宁、iseganan、头孢西丁、头孢曲松、三氯醋酸及其混合物和组合。
35.权利要求30所述的组合物,其中的治疗活性药物是选自以下种的抗病毒剂:喷昔洛韦、阿昔洛韦、更昔洛韦、膦甲酸盐、缬昔洛韦、pleconaril及其混合物和组合。
36.权利要求30所述的组合物,其中的治疗活性药物是杀精子剂壬苯醇醚-9。
37.权利要求30所述的组合物,其中的雄激素物质选自达那唑、睾酮及其混合物和组合。
38.权利要求28所述的组合物,其中外部水不溶相或膜在酸性缓冲相外含有附加的治疗活性药物。
39.权利要求38所述的组合物,其中外相或膜中的附加的治疗活性药物是微粉化的,并具有在约0.5微米至小于60.0微米范围内的粒径。
40.权利要求38所述的组合物,其中外相或膜中的附加的治疗活性药物是未微粉化的。
41.权利要求38所述的组合物,其中外相或膜中的附加的治疗活性药物是微粉化和未微粉化的。
42.权利要求41所述的组合物,其中酸性缓冲相中和酸性缓冲相之外的微粉化药物与未微粉化的药物的比例为约0.1至约1,000;其中治疗活性药物的释放速率为约0.1小时至约72小时。
43.权利要求28所述的组合物,其中的酸性缓冲相具有高于300±10毫渗克分子/升的渗透压。
44.权利要求28所述的组合物,其中的酸性缓冲相具有低于300±10毫渗克分子/升的渗透压。
45.权利要求28所述的组合物,其中的酸性缓冲相具有等于300±10毫渗克分子/升的渗透压。
46.权利要求28所述的组合物,其中的治疗活性药物是表面活性药物。
47.权利要求46所述的组合物,其中的表面活性药物是磷酸克林霉素。
48.一种pH基本为中性的阴道药物释放系统,其中包含:
pH基本为中性的乳剂,它有具有两相的药球:内部的水溶相,和外部的水不溶相或膜;
所述的内部水溶相包含其本身pH为约2.0至约6.0的酸性缓冲相和一或多种治疗活性药物,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的一或多种所述的治疗活性药物。
49.权利要求48所述的组合物,其中的酸性缓冲相其本身pH在约2.5至约5.5之间。
50.治疗阴道疾病的方法,包括给病人使用一种pH基本为中性的阴道药物释放系统,其中含有:
pH基本为中性的乳剂,它有具有两相的药球:内部的水溶相和外部的水不溶相或膜;
所述的内部水溶相包含含有一或多种治疗活性药物的酸性缓冲相,其中酸性缓冲相包含独立的或与其它的缓冲剂结合的一或多种所述的治疗活性药物;
其中酸性缓冲相为等渗、高渗或低渗;并且
其中的治疗活性药物具有在约0.1微米至小于60.0微米范围内的粒径。
51.权利要求50的方法,其中的阴道疾病包括以下引起的感染:假丝酵母、肠球菌、链球菌、葡萄球菌、尿路病原体、大肠杆菌、克雷白氏杆菌属、梭菌、动弯杆菌、加德纳氏菌属、普雷沃氏菌、假单孢属细菌、原虫、支原体属、衣菌属、HIV、HPV、疱疹、非特异性阴道炎、淋病奈瑟氏球菌、阴道毛滴虫、砂眼衣原体,及其混合和组合。
52.权利要求50所述方法,其中的等渗酸性缓冲相通过扩散从药球中释放治疗活性药物。
53.权利要求50所述的方法,其中的治疗活性药物在用药后约0.1小时至约168小时内释放到作用部位。
54.权利要求50所述方法,其中的高渗酸性缓冲相通过药球的破裂从药球中释放治疗活性药物。
55.权利要求54所述方法,其中的治疗活性药物在用药后约5分钟至约60分钟内释放到作用部位。
56.权利要求50所述方法,其中的低渗酸性缓冲相通过扩散和渗透从药球中释放治疗活性药物。
57.权利要求56所述方法,其中的治疗活性药物在用药后持续向作用部位释放至少约1小时。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/101,014 US6899890B2 (en) | 2002-03-20 | 2002-03-20 | Bioadhesive drug delivery system |
US10/101014 | 2002-03-20 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2010105156408A Division CN102048689A (zh) | 2002-03-20 | 2002-07-29 | 生物粘着性药物释放系统 |
CNA2007101048008A Division CN101045034A (zh) | 2002-03-20 | 2002-07-29 | 生物粘着性药物释放系统 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1444926A true CN1444926A (zh) | 2003-10-01 |
Family
ID=22282669
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA2007101048008A Pending CN101045034A (zh) | 2002-03-20 | 2002-07-29 | 生物粘着性药物释放系统 |
CN02127087A Pending CN1444926A (zh) | 2002-03-20 | 2002-07-29 | 生物粘着性药物释放系统 |
CN2010105156408A Pending CN102048689A (zh) | 2002-03-20 | 2002-07-29 | 生物粘着性药物释放系统 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA2007101048008A Pending CN101045034A (zh) | 2002-03-20 | 2002-07-29 | 生物粘着性药物释放系统 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2010105156408A Pending CN102048689A (zh) | 2002-03-20 | 2002-07-29 | 生物粘着性药物释放系统 |
Country Status (17)
Country | Link |
---|---|
US (1) | US6899890B2 (zh) |
EP (1) | EP1494630A4 (zh) |
JP (1) | JP4462818B2 (zh) |
KR (2) | KR20030076159A (zh) |
CN (3) | CN101045034A (zh) |
AR (1) | AR039037A1 (zh) |
AU (2) | AU2002300175B2 (zh) |
BR (1) | BR0202767A (zh) |
CA (1) | CA2392473C (zh) |
FR (1) | FR2837389A1 (zh) |
HU (1) | HUP0203102A3 (zh) |
IT (1) | ITMI20021660A1 (zh) |
MX (1) | MXPA02006943A (zh) |
PT (1) | PT102854B (zh) |
RU (1) | RU2320322C2 (zh) |
WO (1) | WO2003079981A2 (zh) |
ZA (1) | ZA200407535B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110799198A (zh) * | 2016-11-30 | 2020-02-14 | 普罗生物瑞士股份公司 | 用于稳定阴道液的酸度和氧化还原状态的基于合适的生化组合物的泌尿生殖器医疗设备制剂 |
Families Citing this family (61)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060189552A1 (en) * | 2000-12-12 | 2006-08-24 | Mohan Vishnupad | Dispenser for dispensing three or more actives |
US7060732B2 (en) * | 2000-12-12 | 2006-06-13 | Imaginative Research Associates, Inc. | Antibiotic/benzoyl peroxide dispenser |
US6899890B2 (en) * | 2002-03-20 | 2005-05-31 | Kv Pharmaceutical Company | Bioadhesive drug delivery system |
US20060083759A1 (en) * | 2002-07-17 | 2006-04-20 | Aleksander Resman | Stabilization of the profile of release of active substances from a formulation |
US20050037033A1 (en) * | 2003-05-23 | 2005-02-17 | Program For Appropriate Technology In Health | Microbicidal compositions and methods and use |
ITTO20030404A1 (it) * | 2003-05-30 | 2004-11-30 | Rottapharm S R L | Composizione per il ripristino dell'ecosistema vaginale |
GB0315671D0 (en) * | 2003-07-04 | 2003-08-13 | Chelsea And Westminster Nhs Tr | Improvements in or relating to organic compounds |
US20060140990A1 (en) | 2003-09-19 | 2006-06-29 | Drugtech Corporation | Composition for topical treatment of mixed vaginal infections |
BRPI0414500A (pt) * | 2003-09-19 | 2006-11-07 | Drugtech Corp | formulação farmacêutica composição para tratar uma infecção vaginal, e, métodos para tratar uma infecção vaginal, para estabilizar uma formulação de clindamicina, para tratar ou prevenir uma recorrência de uma infecção vaginal em uma paciente e para tratar condições vaginais |
EP1706128B1 (en) * | 2003-12-08 | 2010-07-21 | CPEX Pharmaceuticals, Inc. | Pharmaceutical compositions and methods for insulin treatment |
US8057433B2 (en) | 2004-07-08 | 2011-11-15 | Drugtech Corporation | Delivery system |
UA93354C2 (ru) * | 2004-07-09 | 2011-02-10 | Гилиад Сайенсиз, Инк. | Местный противовирусный препарат |
US20060093675A1 (en) * | 2004-10-29 | 2006-05-04 | Mathew Ebmeier | Intravaginal treatment of vaginal infections with metronidazole compositions |
US7619008B2 (en) * | 2004-11-12 | 2009-11-17 | Kimberly-Clark Worldwide, Inc. | Xylitol for treatment of vaginal infections |
US20060217443A1 (en) * | 2005-03-28 | 2006-09-28 | Kimberly-Clark Worldwide, Inc. | Method for preventing and/or treating vaginal and vulval infections |
CA2609754C (en) | 2005-04-27 | 2012-01-10 | Shenzhen Phlora Biotechnology Limited | Compositions of benzoic acid and saccharides for regulating and maintaining bacterial flora and acidity in the vagina |
WO2006121429A1 (en) * | 2005-05-06 | 2006-11-16 | Imaginative Research Associates, Inc. | Clindamycin compositions and delivery system therefor |
CN101170993A (zh) * | 2005-05-09 | 2008-04-30 | 药物技术公司 | 修饰释放的药物组合物 |
US7786176B2 (en) * | 2005-07-29 | 2010-08-31 | Kimberly-Clark Worldwide, Inc. | Vaginal treatment composition containing xylitol |
JP5265359B2 (ja) | 2005-08-11 | 2013-08-14 | マサチューセッツ インスティテュート オブ テクノロジー | 膀胱内薬物送達デバイスおよび方法 |
AR056453A1 (es) * | 2005-08-12 | 2007-10-10 | Drug Tech Corp | Composiciones con estrogeno y metodos terapeuticos para su uso |
EA200870153A1 (ru) * | 2006-01-05 | 2008-12-30 | Драгтек Корпорейшн | Композиция и способ ее использования |
KR20080083190A (ko) * | 2006-01-05 | 2008-09-16 | 드러그테크 코포레이션 | 외음질 표면에 생체접착을 위한 약물 전달 시스템 |
JP2009526064A (ja) * | 2006-02-09 | 2009-07-16 | シェーリング コーポレイション | 薬学的調合物 |
EP1872775A1 (en) * | 2006-06-29 | 2008-01-02 | Polichem S.A. | Use of a hydrophilic matrix comprising a polyacrylic acid derivative, a cellulose ether and a disintegrant for the manufacture of a medicament for treating female genital disorders |
US20080003262A1 (en) * | 2006-06-30 | 2008-01-03 | Drugtech Corporation | Compositions and therapeutic methods of use |
US20080085877A1 (en) * | 2006-08-10 | 2008-04-10 | Drugtech Corporation | Therapeutic methods of using estrogen compositions |
US20080268022A1 (en) * | 2007-02-23 | 2008-10-30 | Mccabe R Tyler | Mehtods for treating and preventing ailments caused by human papillomavirus |
WO2008144143A1 (en) * | 2007-05-14 | 2008-11-27 | Drugtech Corporation | Endometriosis treatment |
EP1994938A1 (en) * | 2007-05-21 | 2008-11-26 | Combinature Biopharm AG | New lipoglycodepsipeptide compositions |
EP2231254B9 (en) * | 2007-12-11 | 2015-04-08 | Massachusetts Institute of Technology | Implantable drug delivery device |
US20090238867A1 (en) * | 2007-12-13 | 2009-09-24 | Scott Jenkins | Nanoparticulate Anidulafungin Compositions and Methods for Making the Same |
KR101794899B1 (ko) * | 2008-08-09 | 2017-11-07 | 메사츄세츠 인스티튜트 어브 테크놀로지 | 남성 비뇨생식기 및 주위 조직을 치료하는 방법 및 체내이식형 약물 전달 장치 |
CN102333546B (zh) * | 2009-02-26 | 2014-11-26 | Brain生物技术研究与信息网络股份公司 | 用于在跨角蛋白的局部药物递送中使用表面活性蛋白的组合物、用途和方法 |
CN102470237A (zh) | 2009-06-26 | 2012-05-23 | 塔里斯生物医药公司 | 用于可植入药物递送装置的固体药物片剂 |
US20110008469A1 (en) * | 2009-07-09 | 2011-01-13 | Florida Gulf Coast University | Antimicrobial composition and methods and apparatus for use thereof |
US9017312B2 (en) | 2009-09-10 | 2015-04-28 | Taris Biomedical Llc | Implantable device for controlled drug delivery |
RU2479305C2 (ru) * | 2010-12-06 | 2013-04-20 | Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") | Фармацевтическая композиция для лечения инфекционных воспалительных заболеваний в гинекологии и способ ее получения |
SG191893A1 (en) | 2011-01-10 | 2013-08-30 | Taris Biomedical Inc | Lidocaine regimen for the use of sustained treatment of bladder pain and irritative voiding |
ES2637388T3 (es) | 2011-02-04 | 2017-10-13 | Taris Biomedical, Inc. | Dispositivo implantable para la liberación controlada de un fármaco de baja solubilidad |
WO2012109363A2 (en) | 2011-02-08 | 2012-08-16 | The Johns Hopkins University | Mucus penetrating gene carriers |
UA107155C2 (uk) | 2011-04-04 | 2014-11-25 | Стабільна композиція для лікування герпесвірусних інфекцій | |
AU2012250862B2 (en) | 2011-05-02 | 2015-07-09 | Adare Pharmaceuticals, Inc. | Rapid dissolve tablet compositions for vaginal administration |
CN103841837A (zh) * | 2011-09-19 | 2014-06-04 | 奥米尼埃克蒂夫健康科技有限公司 | 用于制备供人消耗的含番茄红素的油性树脂和番茄红素晶体的有效方法 |
US9180094B2 (en) | 2011-10-12 | 2015-11-10 | The Texas A&M University System | High porosity materials, scaffolds, and method of making |
CN104936620B (zh) * | 2012-01-19 | 2019-08-09 | 约翰霍普金斯大学 | 增强粘膜渗透的纳米粒子调配物 |
EP2874824A1 (en) | 2012-07-23 | 2015-05-27 | Crayola LLC | Dissolvable films and methods of using the same |
RU2538703C2 (ru) * | 2013-03-12 | 2015-01-10 | Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") | Фармацевтическая композиция для лечения вагинального кандидоза и способ ее получения |
SG10201708522SA (en) | 2013-03-15 | 2017-12-28 | Taris Biomedical Llc | Drug delivery devices with drug-permeable component and methods |
WO2014192791A1 (ja) * | 2013-05-30 | 2014-12-04 | 大正製薬株式会社 | 坐剤 |
CA2919215C (en) | 2013-08-19 | 2022-11-29 | Taris Biomedical Llc | Multi-unit drug delivery devices and methods |
US10363215B2 (en) | 2013-11-08 | 2019-07-30 | The Texas A&M University System | Porous microparticles with high loading efficiencies |
US20150238549A1 (en) * | 2014-02-27 | 2015-08-27 | Mak Wood, Inc. | Probiotic dosage units |
US10065029B2 (en) | 2014-03-03 | 2018-09-04 | Cook Medical Technologies Llc | Mechanical dilator |
WO2015175545A1 (en) | 2014-05-12 | 2015-11-19 | The Johns Hopkins University | Highly stable biodegradable gene vector platforms for overcoming biological barriers |
JP7425534B2 (ja) | 2015-04-23 | 2024-01-31 | タリス バイオメディカル エルエルシー | 薬物透過性構成要素を有する薬物送達デバイス及び方法 |
RU2017146425A (ru) | 2015-05-29 | 2019-07-02 | Ив Фарма Лтд. | Pн-зависимые вагинальные композиции и способы лечения вагинальных нарушений |
AU2015410635B2 (en) | 2015-09-29 | 2021-08-19 | Kimberly-Clark Worldwide, Inc. | Synergistic composition for maintenance of healthy balance of microflora |
KR101880179B1 (ko) * | 2016-11-03 | 2018-07-20 | 한국생명공학연구원 | 미카펀진(micafungin) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 항바이러스용 약학적 조성물 |
CA3123051A1 (en) * | 2018-12-19 | 2020-06-25 | Healthy Cow Corporation | Ready-to-use probiotic compositions and uses thereof |
US11529346B2 (en) * | 2020-06-18 | 2022-12-20 | National Medical Supply, LLC | Vaginal gel |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3988508A (en) | 1973-03-08 | 1976-10-26 | Petrolite Corporation | High internal phase ratio emulsion polymers |
DE3321043A1 (de) * | 1983-06-10 | 1984-12-13 | Bayer Ag, 5090 Leverkusen | Antimykotische mittel fuer einmalige gynaekologische behandlung |
US4551148A (en) | 1982-09-07 | 1985-11-05 | Kv Pharmaceutical Company | Vaginal delivery systems and their methods of preparation and use |
US5266329A (en) | 1985-10-31 | 1993-11-30 | Kv Pharmaceutical Company | Vaginal delivery system |
US5536743A (en) * | 1988-01-15 | 1996-07-16 | Curatek Pharmaceuticals Limited Partnership | Intravaginal treatment of vaginal infections with buffered metronidazole compositions |
US4895452A (en) | 1988-03-03 | 1990-01-23 | Micro-Pak, Inc. | Method and apparatus for producing lipid vesicles |
US5055303A (en) | 1989-01-31 | 1991-10-08 | Kv Pharmaceutical Company | Solid controlled release bioadherent emulsions |
CA1337279C (en) | 1989-06-06 | 1995-10-10 | Robert J. Borgman | Intravaginal treatment of vaginal infections with buffered metronidazole compositions |
US5298246A (en) | 1991-01-09 | 1994-03-29 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Stable pharmaceutical composition and method for its production |
ATE154241T1 (de) | 1991-10-01 | 1997-06-15 | Takeda Chemical Industries Ltd | Mikropartikeln-zusammenfassung zur verlängerten freigabe und herstellung derselbe |
US5189070A (en) | 1992-05-29 | 1993-02-23 | Shell Oil Company | Process for preparing low density porous crosslinked polymeric materials |
US6191105B1 (en) | 1993-05-10 | 2001-02-20 | Protein Delivery, Inc. | Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin |
US5576016A (en) | 1993-05-18 | 1996-11-19 | Pharmos Corporation | Solid fat nanoemulsions as drug delivery vehicles |
US5744155A (en) | 1993-08-13 | 1998-04-28 | Friedman; Doron | Bioadhesive emulsion preparations for enhanced drug delivery |
US5470885A (en) | 1993-09-29 | 1995-11-28 | The Research Foundation Of The State University Of New York | Fluorocarbons as anti-inflammatory agents |
TW438601B (en) | 1994-05-18 | 2001-06-07 | Janssen Pharmaceutica Nv | New mucoadhesive emulsion compositions and a process for the preparation thereof |
US5980936A (en) | 1997-08-07 | 1999-11-09 | Alliance Pharmaceutical Corp. | Multiple emulsions comprising a hydrophobic continuous phase |
US5877216A (en) | 1997-10-28 | 1999-03-02 | Vivus, Incorporated | Treatment of female sexual dysfunction |
WO1999021562A1 (en) | 1997-10-28 | 1999-05-06 | Asivi, Llc | Treatment of female sexual dysfunction |
US6899890B2 (en) * | 2002-03-20 | 2005-05-31 | Kv Pharmaceutical Company | Bioadhesive drug delivery system |
-
2002
- 2002-03-20 US US10/101,014 patent/US6899890B2/en not_active Expired - Lifetime
- 2002-06-28 CA CA002392473A patent/CA2392473C/en not_active Expired - Lifetime
- 2002-07-10 KR KR1020020039940A patent/KR20030076159A/ko not_active Application Discontinuation
- 2002-07-15 AU AU2002300175A patent/AU2002300175B2/en not_active Ceased
- 2002-07-15 MX MXPA02006943A patent/MXPA02006943A/es active IP Right Grant
- 2002-07-18 BR BR0202767-4A patent/BR0202767A/pt not_active IP Right Cessation
- 2002-07-26 IT IT2002MI001660A patent/ITMI20021660A1/it unknown
- 2002-07-29 CN CNA2007101048008A patent/CN101045034A/zh active Pending
- 2002-07-29 CN CN02127087A patent/CN1444926A/zh active Pending
- 2002-07-29 CN CN2010105156408A patent/CN102048689A/zh active Pending
- 2002-09-12 JP JP2002266381A patent/JP4462818B2/ja not_active Expired - Fee Related
- 2002-09-18 HU HU0203102A patent/HUP0203102A3/hu unknown
- 2002-10-15 PT PT102854A patent/PT102854B/pt not_active IP Right Cessation
- 2002-11-27 FR FR0214858A patent/FR2837389A1/fr active Pending
-
2003
- 2003-03-19 RU RU2004130870/15A patent/RU2320322C2/ru not_active IP Right Cessation
- 2003-03-19 EP EP03714226A patent/EP1494630A4/en not_active Ceased
- 2003-03-19 WO PCT/US2003/008266 patent/WO2003079981A2/en not_active Application Discontinuation
- 2003-03-19 AU AU2003218233A patent/AU2003218233A1/en not_active Abandoned
- 2003-03-20 AR ARP030100979A patent/AR039037A1/es unknown
-
2004
- 2004-09-17 ZA ZA200407535A patent/ZA200407535B/en unknown
-
2008
- 2008-10-29 KR KR1020080106637A patent/KR20080098576A/ko not_active Application Discontinuation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110799198A (zh) * | 2016-11-30 | 2020-02-14 | 普罗生物瑞士股份公司 | 用于稳定阴道液的酸度和氧化还原状态的基于合适的生化组合物的泌尿生殖器医疗设备制剂 |
Also Published As
Publication number | Publication date |
---|---|
ITMI20021660A1 (it) | 2004-01-26 |
AU2003218233A1 (en) | 2003-10-08 |
ZA200407535B (en) | 2006-06-28 |
FR2837389A1 (fr) | 2003-09-26 |
HU0203102D0 (zh) | 2002-11-28 |
BR0202767A (pt) | 2004-05-25 |
JP4462818B2 (ja) | 2010-05-12 |
CN101045034A (zh) | 2007-10-03 |
AR039037A1 (es) | 2005-02-02 |
US6899890B2 (en) | 2005-05-31 |
MXPA02006943A (es) | 2004-12-13 |
AU2002300175B2 (en) | 2004-04-22 |
WO2003079981A3 (en) | 2003-11-06 |
WO2003079981A2 (en) | 2003-10-02 |
CA2392473A1 (en) | 2003-09-20 |
EP1494630A2 (en) | 2005-01-12 |
RU2320322C2 (ru) | 2008-03-27 |
KR20080098576A (ko) | 2008-11-11 |
AU2003218233A8 (en) | 2003-10-08 |
RU2004130870A (ru) | 2005-06-10 |
EP1494630A4 (en) | 2007-03-14 |
PT102854A (pt) | 2003-09-30 |
AU2002300175A1 (en) | 2003-10-09 |
JP2003286193A (ja) | 2003-10-07 |
US20030180366A1 (en) | 2003-09-25 |
CA2392473C (en) | 2007-09-18 |
KR20030076159A (ko) | 2003-09-26 |
CN102048689A (zh) | 2011-05-11 |
PT102854B (pt) | 2004-02-27 |
HUP0203102A3 (en) | 2004-06-28 |
HUP0203102A2 (hu) | 2004-05-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1444926A (zh) | 生物粘着性药物释放系统 | |
JP6682127B2 (ja) | 膣内挿入用可溶性エストラジオールカプセル | |
US9789057B2 (en) | Pharmaceutical delivery system | |
JP2999820B2 (ja) | 緩衝メトロニダゾール組成物による膣感染症の改良された膣内治療 | |
US8703179B2 (en) | Mucosal formulation | |
MX2008001687A (es) | Composiciones de estrogenos y metodos terapeuticos de uso. | |
KR20080091794A (ko) | 국소 사용을 위한 의약 | |
JP2519029B2 (ja) | 腟内送達用製剤 | |
CN102258785A (zh) | 一种缓释释药的药物载体 | |
CN102000339A (zh) | 缓释释药的药物载体 | |
EP1968543A2 (en) | Composition and method of use thereof | |
RU2281102C2 (ru) | Фармацевтическая композиция с антиаллергическим и противовоспалительным действием | |
Tong | ASSESSMENT OF THE PROGESTIN POLYMERIC VAGINAL FILMS BY AN OPTIMIZED SOLVENT-CAST PLATFORM | |
EP4297743A1 (en) | Emulsion for use in the treatment of rosacea | |
WO2016204598A1 (es) | Composición farmaceutica de uso veterinario basada en una suspensión de progesterona en un sistema polimérico, que tiene propiedades de gelificacion in situ | |
MXPA06003131A (en) | Pharmaceutical delivery system |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1055902 Country of ref document: HK |