CN100346775C - 纳米颗粒核芯-壳系统及其在药物和化妆品制剂中的应用 - Google Patents
纳米颗粒核芯-壳系统及其在药物和化妆品制剂中的应用 Download PDFInfo
- Publication number
- CN100346775C CN100346775C CNB998160784A CN99816078A CN100346775C CN 100346775 C CN100346775 C CN 100346775C CN B998160784 A CNB998160784 A CN B998160784A CN 99816078 A CN99816078 A CN 99816078A CN 100346775 C CN100346775 C CN 100346775C
- Authority
- CN
- China
- Prior art keywords
- preparation
- active component
- solution
- polymer
- present
- 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.)
- Expired - Lifetime
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 83
- 239000002537 cosmetic Substances 0.000 title claims abstract description 9
- 239000011258 core-shell material Substances 0.000 title abstract description 6
- 229920000642 polymer Polymers 0.000 claims abstract description 51
- 239000000203 mixture Substances 0.000 claims description 52
- 239000002105 nanoparticle Substances 0.000 claims description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 42
- 239000002245 particle Substances 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 39
- 238000009472 formulation Methods 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 17
- 229920000159 gelatin Polymers 0.000 claims description 14
- 235000019322 gelatine Nutrition 0.000 claims description 14
- 239000000758 substrate Substances 0.000 claims description 12
- 108010010803 Gelatin Proteins 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 239000008273 gelatin Substances 0.000 claims description 11
- 235000011852 gelatine desserts Nutrition 0.000 claims description 11
- 229920001577 copolymer Polymers 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000005018 casein Substances 0.000 claims description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 claims description 2
- 235000021240 caseins Nutrition 0.000 claims description 2
- 229920001688 coating polymer Polymers 0.000 claims description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 2
- 102000011632 Caseins Human genes 0.000 claims 2
- 108010076119 Caseins Proteins 0.000 claims 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims 1
- 229940080237 sodium caseinate Drugs 0.000 claims 1
- 239000011159 matrix material Substances 0.000 abstract description 10
- 239000013543 active substance Substances 0.000 abstract description 9
- 230000000087 stabilizing effect Effects 0.000 abstract 1
- 239000000843 powder Substances 0.000 description 37
- 238000001246 colloidal dispersion Methods 0.000 description 21
- 239000006185 dispersion Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 17
- 238000002156 mixing Methods 0.000 description 15
- 239000002552 dosage form Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- FDSDTBUPSURDBL-LOFNIBRQSA-N canthaxanthin Chemical compound CC=1C(=O)CCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)CCC1(C)C FDSDTBUPSURDBL-LOFNIBRQSA-N 0.000 description 12
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 11
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 11
- 108010036949 Cyclosporine Proteins 0.000 description 11
- 235000013793 astaxanthin Nutrition 0.000 description 11
- 239000001168 astaxanthin Substances 0.000 description 11
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 11
- 229940022405 astaxanthin Drugs 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 229960001265 ciclosporin Drugs 0.000 description 11
- 229940014259 gelatin Drugs 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 9
- 238000000576 coating method Methods 0.000 description 9
- -1 fatty acid ester Chemical class 0.000 description 9
- 239000008187 granular material Substances 0.000 description 9
- 229960000311 ritonavir Drugs 0.000 description 9
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 9
- 229930105110 Cyclosporin A Natural products 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 238000001694 spray drying Methods 0.000 description 8
- 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 7
- 230000008901 benefit Effects 0.000 description 7
- 229930182912 cyclosporin Natural products 0.000 description 7
- 239000008101 lactose Substances 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 239000003381 stabilizer Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 6
- OOUTWVMJGMVRQF-DOYZGLONSA-N Phoenicoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)C(=O)CCC2(C)C OOUTWVMJGMVRQF-DOYZGLONSA-N 0.000 description 6
- 229920001400 block copolymer Polymers 0.000 description 6
- 235000012682 canthaxanthin Nutrition 0.000 description 6
- 239000001659 canthaxanthin Substances 0.000 description 6
- 229940008033 canthaxanthin Drugs 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000084 colloidal system Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 5
- 235000000072 L-ascorbyl-6-palmitate Nutrition 0.000 description 5
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 5
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000002296 dynamic light scattering Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 4
- 229920003139 Eudragit® L 100 Polymers 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 230000002421 anti-septic effect Effects 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 229960004436 budesonide Drugs 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 230000035784 germination Effects 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920001661 Chitosan Polymers 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000000824 cytostatic agent Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000000925 erythroid effect Effects 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 210000001331 nose Anatomy 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- AZJQQNWSSLCLJN-UHFFFAOYSA-N 2-ethoxyquinoline Chemical compound C1=CC=CC2=NC(OCC)=CC=C21 AZJQQNWSSLCLJN-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 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 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
- 206010048768 Dermatosis Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 238000001016 Ostwald ripening Methods 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 229940048053 acrylate Drugs 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 235000021466 carotenoid Nutrition 0.000 description 2
- 229940071162 caseinate Drugs 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920003086 cellulose ether Polymers 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- GJQPMPFPNINLKP-UHFFFAOYSA-N diclofenamide Chemical compound NS(=O)(=O)C1=CC(Cl)=C(Cl)C(S(N)(=O)=O)=C1 GJQPMPFPNINLKP-UHFFFAOYSA-N 0.000 description 2
- 229960005081 diclofenamide Drugs 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 229960002428 fentanyl Drugs 0.000 description 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 2
- 238000005189 flocculation Methods 0.000 description 2
- 230000016615 flocculation Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 239000008131 herbal destillate Substances 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 239000000413 hydrolysate Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000002101 lytic effect Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 210000002850 nasal mucosa Anatomy 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000011505 plaster Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229960000502 poloxamer Drugs 0.000 description 2
- 229920001992 poloxamer 407 Polymers 0.000 description 2
- 229940044476 poloxamer 407 Drugs 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229940065514 poly(lactide) Drugs 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 229920000193 polymethacrylate Polymers 0.000 description 2
- 229920002689 polyvinyl acetate Polymers 0.000 description 2
- 239000011118 polyvinyl acetate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 description 2
- 229960000203 propafenone Drugs 0.000 description 2
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 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
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- 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 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
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 1
- KPJZHOPZRAFDTN-ZRGWGRIASA-N (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)CC)C2)=C3C2=CN(C)C3=C1 KPJZHOPZRAFDTN-ZRGWGRIASA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- QLDPCHZQQIASHX-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;3-(1-methylpyrrolidin-2-yl)pyridine Chemical compound OC(=O)C(O)C(O)C(O)=O.CN1CCCC1C1=CC=CN=C1 QLDPCHZQQIASHX-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
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- PBKADZMAZVCJMR-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;dihydrate Chemical compound O.O.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O PBKADZMAZVCJMR-UHFFFAOYSA-N 0.000 description 1
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- NLJVXZFCYKWXLH-DXTIXLATSA-N 3-[(3r,6s,9s,12s,15s,17s,20s,22r,25s,28s)-20-(2-amino-2-oxoethyl)-9-(3-aminopropyl)-3,22,25-tribenzyl-15-[(4-hydroxyphenyl)methyl]-6-(2-methylpropyl)-2,5,8,11,14,18,21,24,27-nonaoxo-12-propan-2-yl-1,4,7,10,13,16,19,23,26-nonazabicyclo[26.3.0]hentriacontan Chemical compound C([C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(N[C@H](CC=2C=CC=CC=2)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)N1)=O)CC(C)C)C(C)C)C1=CC=C(O)C=C1 NLJVXZFCYKWXLH-DXTIXLATSA-N 0.000 description 1
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 244000144927 Aloe barbadensis Species 0.000 description 1
- 235000002961 Aloe barbadensis Nutrition 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 240000001789 Carlina acaulis Species 0.000 description 1
- 235000005882 Carlina acaulis Nutrition 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 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 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
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 244000133098 Echinacea angustifolia Species 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 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
- VTUSIVBDOCDNHS-UHFFFAOYSA-N Etidocaine Chemical compound CCCN(CC)C(CC)C(=O)NC1=C(C)C=CC=C1C VTUSIVBDOCDNHS-UHFFFAOYSA-N 0.000 description 1
- 244000166124 Eucalyptus globulus Species 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 229940124226 Farnesyltransferase inhibitor Drugs 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- IECPWNUMDGFDKC-UHFFFAOYSA-N Fusicsaeure Natural products C12C(O)CC3C(=C(CCC=C(C)C)C(O)=O)C(OC(C)=O)CC3(C)C1(C)CCC1C2(C)CCC(O)C1C IECPWNUMDGFDKC-UHFFFAOYSA-N 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 239000000899 Gutta-Percha Substances 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-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
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 229920003083 Kollidon® VA64 Polymers 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 229920001732 Lignosulfonate Polymers 0.000 description 1
- 239000004117 Lignosulphonate Substances 0.000 description 1
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- JEYCTXHKTXCGPB-UHFFFAOYSA-N Methaqualone Chemical compound CC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1C JEYCTXHKTXCGPB-UHFFFAOYSA-N 0.000 description 1
- AJXPJJZHWIXJCJ-UHFFFAOYSA-N Methsuximide Chemical compound O=C1N(C)C(=O)CC1(C)C1=CC=CC=C1 AJXPJJZHWIXJCJ-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- NZXKDOXHBHYTKP-UHFFFAOYSA-N Metohexital Chemical compound CCC#CC(C)C1(CC=C)C(=O)NC(=O)N(C)C1=O NZXKDOXHBHYTKP-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000237536 Mytilus edulis Species 0.000 description 1
- IJHNSHDBIRRJRN-UHFFFAOYSA-N N,N-dimethyl-3-phenyl-3-(2-pyridinyl)-1-propanamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=CC=C1 IJHNSHDBIRRJRN-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 240000000342 Palaquium gutta Species 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 244000082490 Proboscidea louisianica Species 0.000 description 1
- 235000015926 Proboscidea louisianica ssp. fragrans Nutrition 0.000 description 1
- 235000015925 Proboscidea louisianica subsp. louisianica Nutrition 0.000 description 1
- BKRGVLQUQGGVSM-KBXCAEBGSA-N Revanil Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=CNC3=C1 BKRGVLQUQGGVSM-KBXCAEBGSA-N 0.000 description 1
- 240000006661 Serenoa repens Species 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 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
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- 108010021006 Tyrothricin Proteins 0.000 description 1
- 240000001717 Vaccinium macrocarpon Species 0.000 description 1
- 235000012545 Vaccinium macrocarpon Nutrition 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 235000001667 Vitex agnus castus Nutrition 0.000 description 1
- 244000063464 Vitex agnus-castus Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 241000736816 Xanthorhiza Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- JHSNLCCMZMGXLK-UHFFFAOYSA-N [3-[3-(2,3-dihydroxypropoxy)-2-hydroxypropoxy]-2-hydroxypropyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COCC(O)COCC(O)CO JHSNLCCMZMGXLK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical class 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
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940124325 anabolic agent Drugs 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 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 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000013590 bulk material Substances 0.000 description 1
- HQIRNZOQPUAHHV-UHFFFAOYSA-N bupranolol Chemical compound CC1=CC=C(Cl)C(OCC(O)CNC(C)(C)C)=C1 HQIRNZOQPUAHHV-UHFFFAOYSA-N 0.000 description 1
- 229960000330 bupranolol Drugs 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- BMRWNKZVCUKKSR-UHFFFAOYSA-N butane-1,2-diol Chemical compound CCC(O)CO BMRWNKZVCUKKSR-UHFFFAOYSA-N 0.000 description 1
- 229960001290 butanilicaine Drugs 0.000 description 1
- VWYQKFLLGRBICZ-UHFFFAOYSA-N butanilicaine Chemical compound CCCCNCC(=O)NC1=C(C)C=CC=C1Cl VWYQKFLLGRBICZ-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 125000001895 carotenoid group Chemical group 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 229960001222 carteolol Drugs 0.000 description 1
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000007766 cera flava Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960003120 clonazepam Drugs 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
- 229960004022 clotrimazole Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000000736 corneocyte Anatomy 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 235000004634 cranberry Nutrition 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- WTYGAUXICFETTC-UHFFFAOYSA-N cyclobarbital Chemical compound C=1CCCCC=1C1(CC)C(=O)NC(=O)NC1=O WTYGAUXICFETTC-UHFFFAOYSA-N 0.000 description 1
- 229960004138 cyclobarbital Drugs 0.000 description 1
- LMKPHJYTFHAGHK-UHFFFAOYSA-N cyclodrine Chemical compound C1CCCC1(O)C(C(=O)OCCN(CC)CC)C1=CC=CC=C1 LMKPHJYTFHAGHK-UHFFFAOYSA-N 0.000 description 1
- 229950000158 cyclodrine Drugs 0.000 description 1
- RHKZVMUBMXGOLL-UHFFFAOYSA-N cyclopentolate hydrochloride Chemical compound Cl.C1CCCC1(O)C(C(=O)OCCN(C)C)C1=CC=CC=C1 RHKZVMUBMXGOLL-UHFFFAOYSA-N 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- QERUYFVNIOLCHV-UHFFFAOYSA-N darodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC2=NON=C12 QERUYFVNIOLCHV-UHFFFAOYSA-N 0.000 description 1
- 229950009702 darodipine Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229960004704 dihydroergotamine Drugs 0.000 description 1
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 description 1
- OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 description 1
- 229960001992 dimetindene Drugs 0.000 description 1
- MVMQESMQSYOVGV-UHFFFAOYSA-N dimetindene Chemical compound CN(C)CCC=1CC2=CC=CC=C2C=1C(C)C1=CC=CC=N1 MVMQESMQSYOVGV-UHFFFAOYSA-N 0.000 description 1
- 229940072271 diprivan Drugs 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960005178 doxylamine Drugs 0.000 description 1
- HCFDWZZGGLSKEP-UHFFFAOYSA-N doxylamine Chemical compound C=1C=CC=NC=1C(C)(OCCN(C)C)C1=CC=CC=C1 HCFDWZZGGLSKEP-UHFFFAOYSA-N 0.000 description 1
- RMEDXOLNCUSCGS-UHFFFAOYSA-N droperidol Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CC=C(N2C(NC3=CC=CC=C32)=O)CC1 RMEDXOLNCUSCGS-UHFFFAOYSA-N 0.000 description 1
- 229960000394 droperidol Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- XACKNLSZYYIACO-DJLDLDEBSA-N edoxudine Chemical compound O=C1NC(=O)C(CC)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XACKNLSZYYIACO-DJLDLDEBSA-N 0.000 description 1
- 229960002030 edoxudine Drugs 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 229960004943 ergotamine Drugs 0.000 description 1
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 1
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960003976 etidocaine Drugs 0.000 description 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 229960001690 etomidate Drugs 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 229960002011 fludrocortisone Drugs 0.000 description 1
- AAXVEMMRQDVLJB-BULBTXNYSA-N fludrocortisone Chemical compound O=C1CC[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 AAXVEMMRQDVLJB-BULBTXNYSA-N 0.000 description 1
- 229960003973 fluocortolone Drugs 0.000 description 1
- GAKMQHDJQHZUTJ-ULHLPKEOSA-N fluocortolone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@H](C(=O)CO)[C@@]2(C)C[C@@H]1O GAKMQHDJQHZUTJ-ULHLPKEOSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000009246 food effect Effects 0.000 description 1
- 235000021471 food effect Nutrition 0.000 description 1
- 229960003704 framycetin Drugs 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 229960004675 fusidic acid Drugs 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000005679 goldenseal Nutrition 0.000 description 1
- 239000000745 gonadal hormone Substances 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical class C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 239000002474 gonadorelin antagonist Substances 0.000 description 1
- 239000002434 gonadorelin derivative Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229920000588 gutta-percha Polymers 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 239000000416 hydrocolloid Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
- 229960001410 hydromorphone Drugs 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229960001936 indinavir Drugs 0.000 description 1
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 108010059642 isinglass Proteins 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N iso-butene Natural products CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229960004427 isradipine Drugs 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 229960000831 levobunolol Drugs 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- 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 description 1
- USSIQXCVUWKGNF-QGZVFWFLSA-N levomethadone Chemical group C=1C=CC=CC=1C(C[C@@H](C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-QGZVFWFLSA-N 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 235000019357 lignosulphonate Nutrition 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229960003587 lisuride Drugs 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 235000012661 lycopene Nutrition 0.000 description 1
- 239000001751 lycopene Substances 0.000 description 1
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 1
- 229960004999 lycopene Drugs 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 229960001474 meclozine Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229960003729 mesuximide Drugs 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229960002803 methaqualone Drugs 0.000 description 1
- 229960002683 methohexital Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960001186 methysergide Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 229960003632 minoxidil Drugs 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229910052627 muscovite Inorganic materials 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 238000002670 nicotine replacement therapy Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229960003502 oxybuprocaine Drugs 0.000 description 1
- CMHHMUWAYWTMGS-UHFFFAOYSA-N oxybuprocaine Chemical compound CCCCOC1=CC(C(=O)OCCN(CC)CC)=CC=C1N CMHHMUWAYWTMGS-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- RXBWRFDZXRAEJT-SZNOJMITSA-N palinavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)C(C)C)[C@H](O)CN1[C@@H](C[C@@H](CC1)OCC=1C=CN=CC=1)C(=O)NC(C)(C)C)C1=CC=CC=C1 RXBWRFDZXRAEJT-SZNOJMITSA-N 0.000 description 1
- 229950006460 palinavir Drugs 0.000 description 1
- PXDJXZJSCPSGGI-UHFFFAOYSA-N palmityl palmitate Chemical compound CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229960001190 pheniramine Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 229960001029 pholedrine Drugs 0.000 description 1
- SBUQZKJEOOQSBV-UHFFFAOYSA-N pholedrine Chemical compound CNC(C)CC1=CC=C(O)C=C1 SBUQZKJEOOQSBV-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 229940068170 pirinitramide Drugs 0.000 description 1
- IHEHEFLXQFOQJO-UHFFFAOYSA-N piritramide Chemical compound C1CC(C(=O)N)(N2CCCCC2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 IHEHEFLXQFOQJO-UHFFFAOYSA-N 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000867 polyelectrolyte Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 238000000710 polymer precipitation Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 229960004134 propofol Drugs 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- VMSKYEUTOGMGTQ-UHFFFAOYSA-N quinoline;thiophene Chemical compound C=1C=CSC=1.N1=CC=CC2=CC=CC=C21 VMSKYEUTOGMGTQ-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 229960004380 tramadol Drugs 0.000 description 1
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 229960003281 tyrothricin Drugs 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000004736 wide-angle X-ray diffraction Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/11—Encapsulated compositions
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/413—Nanosized, i.e. having sizes below 100 nm
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Abstract
药物和化妆品活性物质的纳米颗粒制剂,所述纳米颗粒制剂具有核芯-壳结构,其中活性成分以X-射线非晶形形式与聚合物基质一起存在,并且壳由稳定包衣基质组成。
Description
本发明涉及药物活性成分的纳米颗粒制剂,所述纳米颗粒制剂具有核芯/壳结构,其中活性成分以X-射线非晶形形式与至少一种聚合物一起存在于核芯中,并且壳由聚合包衣基质组成。
EP-A 425892公开了一种改善具有肽键的药物活性成分的生物利用度的方法,其中是将活性成分在水可溶混有机溶剂中的溶液与水胶体迅速混合,这样活性成分以胶体形式沉淀出来。
EP-A 276735描述了活性成分颗粒,所述颗粒包封在保护胶体中,并且在颗粒内活性成分分散在油相中。然而,在油相中经常会产生相容性问题。
EP-A-0169公开了低水溶性物质的颗粒药物制剂,所述制剂是通过向活性成分的溶液中加入沉淀溶液后形成沉淀而获得的。
WO 93/10767描述了肽类药物的口服给药剂型,其中在该剂型中,药物掺合到明胶基质中,形成的胶体颗粒具有中性电荷。然而,这种剂型的缺点是其易于絮凝。
EP-A 0605497描述了其中活性成分稳定在脂质基质中的纳米颗粒。然而,脂质基质在剪切力下是不稳定的,从而可能在进一步加工中产生问题。
DE-A 4440337描述了用表面活性剂稳定的纳米悬浮剂的制备。然而,在某些情况下,高的表面活性剂浓度在生理上是不可接受的。
US 5145684和US 5399363描述了通过特别研磨加工来制备晶态纳米颗粒。然而,晶态纳米颗粒的生物利用度通常较差,并且它们还会产生由于一些活性成分的多晶形而带来的问题。
US 4826689描述了一种沉淀方法,其中获得了没有进一步加入或仅加入少量表面活性剂就得到稳定的非晶形球形颗粒。这种系统的剪切稳定性和灭菌可能性都较小。
EP-A 275796描述了胶体可分散系统的制备,其中所述系统具有粒径低于500nm的球形颗粒,该颗粒具有基质结构,但不是核芯/壳结构。
WO 97/14407描述了通过膨胀从在两亲物存在下的压缩气体、液体或超临界流体中的溶剂中制备纳米颗粒。
DE 3742473C2描述了环孢素固体颗粒与维持该颗粒分散度的稳定剂的水溶胶。在这些水溶胶中,颗粒粒径在胶体粒径范围内。该文献指出,所述水溶胶颗粒由活性成分物料组成。
然而,这些水溶胶的缺点是,水溶胶颗粒的粒径随着时间的延长显著增加。当水溶胶的分散相含有活性成分溶剂时,这种现象尤其明显。当制备水溶胶颗粒时,必须使用这种活性成分溶剂,并且然后必须将其尽可能快地除去。
水溶胶颗粒的生长是由于所谓奥斯特瓦尔德熟化,在这种熟化作用下,活性成分分子经由分散相从小水溶胶颗粒转移到大水溶胶颗粒上。这就意味着较小颗粒缓慢溶解,而较大颗粒缓慢生长。因为活性成分环孢素即使在不含溶剂的水中也会有轻微的残余溶解,所以即使在这种情况下也不能阻止水溶胶颗粒生长。
由于纳米颗粒系统的稳定性,活性成分以稳定的非晶形形式存在,并且在大量药物剂型中有着广泛应用,但是仍然有改进空间。
本发明的目的是发现改进的含有活性成分的纳米颗粒制剂。
我们已经发现,本发明的目的可通过提供下述制剂而得以实现:药物活性成分的纳米颗粒制剂,所述纳米颗粒制剂具有核芯/壳结构,其中活性成分以在聚合物基质中的X-射线非晶形形式存在于核芯中,并且壳由具有保护胶体特性的聚合物的稳定包衣基质组成。
在所述核芯中优选具有至少两个单独相,一个相由活性成分的不连续X-射线非晶形颗粒组成,另一个相是活性成分在一种或多种聚合物中的分子分散体。核芯聚合物与活性成分的用量的比例基本上决定了核芯是一个相还是两个相。
决定性因素是,当活性成分颗粒的粒径下降时,作用在物质上使其溶解的力会增加。这导致饱和溶解度增加。依据Noyes-Whitney,饱和溶解度增加会导致溶解速度提高。另一因素是生物活性物质以能量不稳定的、亚稳状态存在于本发明制剂中。如果纳米颗粒不足够稳定,在有些情况下可导致自发结晶,并且活性成分从稳定形式沉淀出来。
因此,除了稳定的壳结构之外,还要找到能经得起操作,例如混合到霜剂或膏剂内、在化妆品制剂中均化、以及灭菌期间的压力和剪切应力的溶液。
令人惊奇的是,本发明胶体活性成分制剂的水溶胶颗粒生长比基本上仅由在胶体颗粒核芯中的活性成分物料组成的已知活性成分制剂明显降低。在溶解活性成分的溶剂存在下制备含水水溶胶1小时后,颗粒生长因数为4-小于10。对于不含任何溶解活性成分的溶剂的含水水溶胶,颗粒生长降低因数为1.5-5。
存在于本发明活性成分制剂中的胶体颗粒具有包封颗粒核芯的聚合物包衣。该聚合物包衣的作用是将颗粒稳定在其胶体状态以防止多相颗粒生长(聚集、絮凝等)。
此外,存在于本发明活性成分制剂中的胶体颗粒具有活性成分与聚合物的核芯。在所述核芯内部的活性成分是以X-射线非晶形形式存在。在本发明活性成分制剂中,基本上没有任何可检测到的(X-射线衍射)结晶活性成分部分。特别是,在颗粒内部的聚合物有助于将活性成分保持在其非结晶状态和稳定关于均相颗粒生长(奥斯特瓦尔德熟化)的胶体结构。
对于本发明壳的包衣基质,合适的聚合稳定剂是可膨胀的保护胶体剂例如牛、猪或鱼明胶、淀粉、糊精、果胶、阿拉伯胶、木素磺酸盐、脱乙酰壳多糖、聚苯乙烯磺酸酯、藻酸盐、酪蛋白、酪蛋白酸盐、甲基纤维素、羧甲基纤维素、羟丙基纤维素、奶粉、葡聚糖、全奶、脱脂奶或这些保护胶体剂的混合物。基于下述单体的均聚物和共聚物也是合适的:氧化乙烯、氧化丙烯、丙烯酸、马来酸酐、乳酸、N-乙烯吡咯烷酮、乙酸乙烯酯、α-天冬氨酸和β-天冬氨酸。特别优选使用一种上述类型明胶,尤其是用酸或碱降解的、Bloom数为0-250的明胶。非常特别优选明胶A100、A200、B100和B200,以及用酶降解的、Bloom数为0、分子量为15000-25000D的低分子量明胶,例如Collagel A和Gelitasol P(Stoess,Eberbach供给),以及这些类型明胶的混合物。
本发明制剂还含有低分子量表面活性化合物。特别合适的是两亲型化合物或这类化合物的混合物。原则上讲,HLB为5-20的所有表面活性剂都是合适的。合适的表面活性物质的实例有:长链脂肪酸与抗坏血酸的酯,脂肪酸的一甘油酯和二甘油酯及其乙氧基化产物,一脂肪酸甘油酯与乙酸、柠檬酸、乳酸或二乙酰基酒石酸的酯,聚甘油脂肪酸酯例如三甘油一硬脂酸酯,脱水山梨醇脂肪酸酯,丙二醇脂肪酸酯,2-(2′-硬脂酰基乳酰基)乳酸盐和卵磷脂。特别优选使用棕榈酸抗坏血酸酯。
原则上讲,存在于本发明活性成分制剂颗粒的核芯中的合适聚合组分可以是在0-240℃温度下、在1-100巴压力下、在0-14的pH或最高达10mol/l的离子强度下不溶于或仅部分溶于水或水溶液或水/溶剂混合物中的所有聚合物。
在这一点上,不溶于或仅部分溶于是表示聚合物在水或水与有机溶剂的混合物中的第二维里系数为低于0的值(参见M.D.Lechner,“Makromolekulare Chemie”,Birkhuser Verlag,Basle,pp.170-175)。第二维里系数能提供聚合物在溶剂(混合物)中的行为信息,其可通过实验测定,例如通过光散射测定或通过确定渗透压来测定。该系数的单位是(mol-l)/g2。
可以使用一种或多种聚合物。所用聚合物的分子量为1000-10000000g/mol、优选为1000-1000000g/mol。所有适用于药物和化妆品的聚合物原则上都是合适的。
特别适用的聚合物是溶于水可混溶有机溶剂、但是在0-240℃不溶于或仅部分溶于水或水溶液或水/溶剂混合物的聚合物。可提及下述聚合物以举例说明,但是并不限于这些聚合物:
聚(乙烯基醚)例如聚(苄氧基乙烯),聚(乙烯醇缩醛),聚(乙烯基酮),聚(烯丙醇),聚(乙烯基酯)例如聚(乙酸乙烯酯),聚(四氢呋喃),聚(戊二醛),聚(碳酸酯),聚(酯),聚(硅氧烷),D,L-聚(丙交酯),聚(丙交酯),聚(乙交酯),聚(D,L-丙交酯-共聚-乙交酯),聚(酰胺),聚(哌嗪),聚(酸酐)例如聚(异丁烯酸酐),古塔胶,纤维素醚例如甲基纤维素(取代度为3-10%)、乙基纤维素、丁基纤维素,纤维素酯例如乙酸纤维素,或淀粉。特别是上述聚合物的单体的共聚物和嵌段共聚物。此外还有聚酯与羟基羧酸以及直链和星形聚乙二醇的共聚物以及嵌段共聚物,例如D,L-聚(丙交酯)与聚乙二醇或聚(乙交酯)的AB和ABA嵌段共聚物。
特别合适的是在0-240℃在水或水溶液或水/溶剂混合物中有溶混性上限和/或下限的聚合物,即可通过增加或降低温度将这些聚合物从相应的溶液中沉淀出来。可提及下述聚合物以举例说明,但是并不限于这些聚合物:
聚(丙烯酰胺)、聚(异丁烯酰胺),例如聚(N-异丙基丙烯酰胺)、聚(N,N-二甲基丙烯酰胺)、聚(N-(1,1-二甲基-3-氧代丁基)丙烯酰胺),聚(甲氧基乙烯),聚(乙烯醇),乙酰化聚(乙烯醇),聚(氧化乙烯),纤维素醚例如甲基纤维素(取代度为20-40%)、异丙基纤维素,纤维素酯,淀粉,改性淀粉例如甲基醚淀粉,阿拉伯胶,和上述化合物的单体的共聚物或嵌段共聚物。特别是基于氧化乙烯与氧化丙烯的AB或ABA嵌段共聚物,例如泊咯沙姆如泊咯沙姆188和泊咯沙姆407。
可通过在0-240℃改变pH或离子强度而从其在水或水溶液或水/溶剂混合物内的相应溶液中沉淀出来的聚合物也是特别合适的。可提及下述聚合物以举例说明,但是并不限于这些聚合物:
藻酸盐,脱乙酰壳多糖,壳多糖,虫胶,聚电解质,具有仲氨基、叔氨基或季氨基的聚(丙烯酸)、聚(异丁烯酸)、聚(异丁烯酸酯),特别是基于不同丙烯酸酯、异丁烯酸酯、异丁烯酸、丙烯酸的共聚物或嵌段共聚物,例如异丁烯酸/异丁烯酸酯共聚物(MA/MAE比例为1∶1或1∶2),或重量比为1∶1的异丁烯酸二甲基氨基乙酯与异丁烯酸酯的共聚物(Eudragit型)。
依据本发明选择各组分的量,以使得本发明制剂含有0.1-70%重量、优选1-40%重量的活性成分,1-80%重量、优选10-60%重量的一种或多种聚合稳定剂(包衣聚合物),0.01-50%重量、优选0.1-30%重量的一种或多种核芯聚合物,和0-50%重量、优选0.5-10%重量的一种或多种低分子量稳定剂。所述重量百分比数据是按干粉计的。
此外,本发明制剂还可以含有抗氧化剂和/或防腐剂以保护活性成分。合适的抗氧化剂或防腐剂的实例有α-生育酚、叔丁基羟基甲苯、叔丁基羟基茴香醚、卵磷脂、乙氧喹、羟基苯甲酸甲酯、对羟基苯甲酸丙酯、山梨酸、苯甲酸钠、或棕榈酸抗坏血酸酯。抗氧化剂或防腐剂的含量可以为占制剂总重量的0-10%。
本发明制剂还可以含有增塑剂以提高终产品的稳定性。合适的增塑剂的实例有糖或糖醇,例如蔗糖、葡萄糖、乳糖、转化糖、山梨醇、甘露醇、木糖醇或甘油。优选使用乳糖作为增塑剂。增塑剂的含量可以为0-50%重量。
其它药物辅料例如粘合剂、崩解剂、矫味剂、维生素、着色剂、润湿剂、影响pH的添加剂(参见H.Sucker等人,PharmazeutischeTechnologie,Thieme-Verlag,Stuttgart 1978)可同样经由有机溶剂或水相加到本发明制剂中。
为了实施本发明方法,首先在合适的溶剂中制备活性成分的溶液,此处所述的溶液是指分子分散真溶液或熔化乳液。根据活性成分,可采用0-250℃和最高达100巴的压力。合适的溶剂是挥发性、热稳定性、且仅含碳、氢、氧、氮和硫的水可混溶有机溶剂。方便起见,它们能与水达到至少10%重量的混溶,并且具有低于200℃的沸点和/或具有少于10个碳原子。合适的醇、酯、酮、醚和缩醛是优选的。非常特别优选使用乙醇、正丙醇、异丙醇、乙酸丁酯、乙酸乙酯、四氢呋喃、丙酮、1,2-丙二醇、1-正丙基醚或1,2-丁二醇1-甲基醚。乙醇、异丙醇和丙酮是非常特别优选的。
在本发明方法的一个实施方案中,将活性成分在所选溶剂中的分子分散溶液与在活性成分制剂颗粒核芯中存在的聚合物制备在一起。该聚合物的特征是不溶于水,或者仅在特定温度、pH或盐范围内部分溶于水。
以该方式制备的活性成分/聚合物溶液的浓度通常为10-500g活性成分/1kg溶剂和0.01-400g聚合物,并且聚合物/活性成分的重量比为0.01∶1-5∶1。在本发明方法优选的实施方案中,将低分子量稳定剂直接加到活性成分/聚合物溶液中。
在此随后的方法步骤中,将活性成分/聚合物溶液与聚合包衣材料的水溶液混合。聚合包衣材料的浓度为0.1-200g/l、优选为1-100g/l。
在本发明方法的另一实施方案中,活性成分在所选溶剂中的分子分散溶液不与在活性成分制剂颗粒核芯中存在的聚合物制备在一起。以该方式制备的活性成分溶液的浓度一般为10-500g活性成分/1kg溶剂。
在随后的方法步骤中,将该溶液与在本发明活性成分制剂颗粒核芯中存在的聚合物的分子水溶液混合。以该方式制备的聚合物溶液的浓度一般为0.01-400g聚合物。选择欲混合的这两种溶液的温度、pH值和盐浓度,以使得在将这两种溶液混合后,活性成分与聚合物变得不溶。在本发明方法优选的实施方案中,将低分子量稳定剂直接加到活性成分溶液中。
在此随后的步骤中,将活性成分/聚合物沉淀与聚合包衣材料的水溶液混合。聚合包衣材料的浓度为0.1-200g/l,优选1-100g/l。
为了使在混合操作中获得的颗粒的粒径最小,建议在环孢素溶液与包衣材料溶液的混合期间采用高机械能量输入。这样的能量输入可例如这样进行:在合适装置中剧烈搅拌或振摇,或者将在压缩喷射器中的这两种组分喷雾到混合室内以实现剧烈混合。
混合操作可分批进行,或者优选连续进行。混合操作可获得沉淀。然后可以通过本身已知方法将所得悬浮液或者胶体转化成干燥粉末,例如采用喷雾干燥、冷冻干燥、或流化床干燥。
当实施本发明方法时,在具体情况下选择的关于不同水/有机溶剂系统、pH值、温度或离子强度的条件可由本领域技术人员通过借助于第二维里系数对适当聚合物进行一些简单测试来确定。
然后可将最初的分散体进行本领域技术人员已知的干燥操作。
因此,制备完成后,可将本发明纳米颗粒系统干燥,例如通过喷雾干燥或冷冻干燥进行干燥,之后将其以实际上相同的粒径分布再分散。这对于其中制剂必须尽可能长地贮存、暴露于极端条件下例如热或冷的条件下,或者从水载体转移到其它作为溶剂的载体中的所有应用有很大优点。这意味着本发明制剂不再受缚于制备它们所用的溶剂。
在将本发明纳米颗粒冷冻干燥时,可加入低温保护剂例如海藻糖或聚乙烯吡咯烷酮类。
因此,依据本发明可获得不丧失其在最初的分散体中获得的性质的干燥粉末。这意味着活性成分的非晶形性质和核芯/壳结构仍得以保持。本发明的另一特征是,当再溶解时,这些分散体具有与其最初的分散体相同的粒径分布,差异为20%,优选<15%。
本发明纳米颗粒分散体的界面张力为20-40mN/m,优选为10-30nM/m。
核芯/壳结构的粒径为0.1-2μm,优选为0.05-0.9μm。
本发明低溶解性活性成分在25℃在水中的溶解度优选低于10mg/ml。
合适的活性成分的实例有:
-止痛剂/抗风湿剂,例如可待因、双氯芬酸、芬太尼、氢吗啡酮、布洛芬、吲哚美辛、左旋美沙酮、吗啡、萘普生、哌腈米特、吡罗昔康、曲马多;
-抗变态反应药,例如阿司咪唑、二甲茚啶、多西拉敏、氯雷他定、氯苯甲嗪、非尼拉敏、特非那定;
-抗生素/化疗剂,例如红霉素、新霉素B、夫西地酸、利福平、四环素、氨苯硫脲、短杆菌素;
-抗癫痫剂,例如卡马西平、氯硝西泮、甲琥胺、苯妥英、丙戊酸;
-抗真菌剂,例如克霉唑、氟康唑、依他康唑;
-钙通道阻断剂,例如达罗地平、伊拉地平;
-类皮质激素类,例如醛固酮、倍他米松、布地奈德、地塞米松、氟可龙、氟氢可的松、羟基可的松、甲基强的松龙、强的松龙;
-安眠药/镇静剂
苯并二氮杂、环巴比妥、甲喹酮、苯巴比妥;
-免疫抑制剂
硫唑嘌呤、环孢菌素;
-局麻药
苯佐卡因、布坦卡因、依替卡因、利多卡因、丁氧普鲁卡因、丁卡因;
-偏头痛药物
二氢麦角胺、麦角胺、麦角乙脲、美西麦角;
-麻醉剂
氟哌利多、依托咪酯、芬太尼、氯胺酮、美索比妥、普鲁泊福、硫喷妥;
-眼科用药
乙酰唑胺、倍他洛尔、布拉洛尔、卡巴胆碱、卡替洛尔、环戊醇乙胺酯、环戊通、双氯非那胺、依度尿苷、后马托品、左布诺洛尔、福来君、吲哚洛尔、噻吗洛尔、托吡卡胺;
-中药
金丝桃、荨麻叶、朝鲜蓟、羊荆、美升麻、猫爪、金雀花、薄荷油、桉树、白屈菜、常春藤、醉椒、紫锥花、缬草、美洲蒲葵提取物、奶蓟、银杏、巴巴多芦荟、蒜、人参、塞润榈、北美黄连、vacciniummacrocarpon或它们的混合物;
-蛋白酶抑制剂
例如噻喹努佛、Indinavir、利托那韦、Nelfinavir、Palinavir、或这些蛋白酶抑制剂的组合;
-性激素及其拮抗剂
Anabolics、雄激素、抗雄激素、雌二醇、Gestagens、黄体酮、雌激素、抗雌激素例如他莫昔芬;
-维生素/抗氧化剂例如类胡萝卜素或类胡萝卜素类似物,例如β-胡萝卜素、斑蝥黄、虾青素、番茄红素或硫辛酸;
-细胞抑制剂/抗转移剂
白消安、卡莫司汀、苯丁酸氮芥、环磷酰胺、达卡巴嗪、更生霉素、雌莫司汀、依托泊苷、氟尿嘧啶、异环磷酰胺、甲氨蝶呤、紫杉醇、长春碱、长春新碱、长春地辛。
原则上讲,本发明纳米颗粒制剂适用于制备所有药物剂型:口服药物剂型,局部施用药物剂型例如皮肤病用、眼病用、肺或鼻用剂型,颊给药剂型,肛门用或阴道内给药剂型,肠内和非胃肠道给药剂型。
因此可将本发明制剂制成片剂、丸剂、药囊、饮用制剂、栓剂、注射液或囊剂填充剂。
因此,可制成在软或硬明胶制剂中的制剂。这些类型制剂代表着多颗粒系统的实例,其中纳米颗粒是软明胶制剂的一个相,基质是另一个相,并且基质相还可以含有另一或相同活性成分。
同样,可将本发明系统置于其它基体中,在这种情况下,其代表着与剩余基质分开的相。这类基体可以是片剂、栓剂、或经肺给药或透皮给药系统中。
关于包埋的非晶形活性成分,还必须提及的活性成分的特别性质是多晶形性。许多活性成分以一种以上的晶形存在。通常可以假定有50%以上的所有活性成分以数种晶形存在。活性成分的所有这些多晶形变型在化学上是相同的,但是具有不同物理性质例如熔点、密度和溶解度。这意味着不同变型还对加工性有影响,并且在大多数情况下还会影响生物利用度。
本发明制剂使得能够以简单方式将活性成分转化成非晶形状态,并且可用作原料和粒径分布很宽的产品以及非晶形散装材料,并因此避免了不同多晶形式的问题以及多晶形带来的涉及溶解度、贮存稳定性和生物利用度的可能缺点。
本发明的目的还是找到用于纳米颗粒非晶形核芯/壳结构的新制剂。令人惊奇的是,改变所用的聚合稳定剂以满足注射产品的要求后,能够获得还具有明胶水解产物的稳定核芯/壳结构。使用这样的明胶水解产物的优点是,能明显降低体内给药(例如静脉内、肌内或皮下给药)的组胺反应。
本发明纳米颗粒使得能够进行无菌制备和无菌过滤。
因为实体瘤能够从血流中过滤出颗粒,所以本发明制剂适于实现肿瘤靶向定位。因此能够在局部获得高浓度积聚的细胞毒害物质。这意味着通过本发明纳米颗粒系统治疗癌症是特别优选的。
对于本发明技术,合适且优选的细胞生长抑制剂是紫杉醇类,例如紫杉酚、顺铂、以及非插入法尼基转移酶抑制剂。
还已知纳米颗粒系统能越过血脑屏障,因此可特别用于治疗CNS障碍。本发明纳米颗粒亦是如此,因此特别适用于治疗CNS障碍。
虽然聚合物重量明显低于在EP-A 425892描述的剂型中的重量,但是仍然能够获得适应要求的稳定产品。与其它方法相比,本发明方法使用少量辅料是一个优点。本发明非晶形核芯/壳纳米颗粒的制剂通常仅由聚合物载体和生物活性物质组成。
由于制备方法,本发明非晶形核芯/壳纳米颗粒还具有另一优点。生物活性物质从溶剂剧烈混合到非溶剂中使其能够引入少量聚合物,这些聚合物之后在形成球形结构期间通过吸附到表面上而聚集在基质内。这有助于稳定非晶形和由此所致的亚稳定状态。具体来说,本发明纳米颗粒包含多相系统,多相系统具有由引起分散的聚合添加剂和非晶形结构组成的外壳,该非晶形结构含有仍然溶解的相同聚合添加剂或用作结晶抑制剂的另一添加剂。
在本发明制剂的非晶形相中,特殊状态是形成液晶系统。
低分子量肽例如LMWH的制剂可通过口服途径给药,并且最好是,同样的制剂还可以作为注射剂给药,而这种注射给药是目前治疗深度静脉血栓形成的标准给药途径。
通常可以说明的是,本发明制剂可以作为单一制剂通过实际上所有的给药方式使用。
本发明制剂还适于结肠靶向定位。
依据本发明,同样可以制得注射贮药库产品。
本发明制剂还可以在非胃肠道营养法中使用。对于这种情况,本发明制剂可特别用于与维生素和氨基酸配制在一起。
在尼古丁替代治疗中,可使用具有例如酒石酸尼古丁或尼古丁碱的本发明制剂,以达到在中断疗法中特别重要的所需血浆峰值。
对于头发生长活性成分例如米诺地尔的局部施用,使用本发明制剂也是特别有利的。本发明制剂由于其结构可更好地到达毛囊。
在本发明制剂的经肺给药中,除了施用哮喘治疗剂例如布地奈德和细胞生长抑制剂以外,还可以特别施用蛋白或肽类治疗剂。其实例有后叶加压素类似物、LHRH拮抗剂、胰高血糖素、甲状旁腺激素、降钙素、胰岛素、LHRH类似物亮丙瑞林、粒细胞集落刺激因子和生长激素。
不仅可以作为粉末给药,而且还可以作为雾化的水悬浮液给药。给药可经由鼻、支气管或肺进行。对于经鼻给药,选取水悬浮液是特别有利的,因为采用水悬浮液可避免由有机溶剂引起的对鼻粘膜的刺激和刺痛感觉。
本发明技术特别适用于白三烯拮抗剂类活性成分。
本发明制剂还可用于将反义活性成分,即具有信使RNA的互补碱基序列的寡聚核苷酸配制成给药制剂。硫代磷酸寡聚核苷酸是优选的。除了局部注射外,还可以作为输注剂或注射剂皮下或静脉内给药,并且也可以口服给药。然而,也可以经皮给药和吸入给药。
本发明制剂还可以以口服剂型使用,口服剂型可作为惯用片剂和胶囊剂使用。应用领域可拓展到特别是制备栓剂,这是通过在搅拌到载体基质过程中本发明纳米颗粒的稳定性得以保证的。对于这种应用,优点是在直肠给药时,可以仅施用有限体积的液体,并且本发明制剂可极好地分散到小体积液体中并被吸收。
以下几点通常可说明本发明剂型的优点:
●较高的生物利用度
●较小的食物效应
●较小的变异性
因为还可以使用丙烯酸酯、卵磷脂、酪蛋白酸盐、明胶、脱乙酰壳多糖、透明质酸或蛤贝粘着蛋白作为壳聚合物,因此可以制备具有纳米粒径的粘液粘合制剂。
纳米颗粒制剂增加的粘合性可最终使得生物利用度提高。这对于经鼻给药特别有利。另一因素是纳米颗粒对鼻粘膜的粘合性对保留时间具有有利作用(否则的话保留时间就会太短),并且可有助于提高生物利用度。
本发明制剂还可以眼用。尤其是在于体温下粘度会增加的凝胶系统中,本发明纳米颗粒系统形成一个单独的相,该相能将活性成分以纳米颗粒非晶形形式递送到眼中,并且在凝胶形成期间在基质中均匀分散。
也可以使用本发明制剂制备用于医学诊断成象例如X-射线法、闪烁造影术、超声、磁共振成象、荧光血管造影术和眼科学的造影剂。
在化妆品或皮肤病用药物中,可使用本发明核芯/壳纳米颗粒来保护水解敏感性活性成分。此外,由于具有小粒径,这类制剂能促进角质层细胞间的渗透。在化妆品领域,本发明制剂可用于香料和美容化妆品制剂中,例如将染料或色素掺入到唇膏、眼线、眼影或指甲油中。本发明制剂还可以在霜剂、凝胶剂和膏剂中使用。
本发明纳米颗粒制剂的特别优点是仅需要少量辅助物质。除了聚合包衣基质和核芯中基质聚合物以外,可以基本上无需其它表面活性辅料。
制剂实施例1
活性成分含量为大约20%重量的利托那韦干粉的制备
a)制备微粉
在25℃,将3g利托那韦搅拌到0.6g棕榈酸抗坏血酸酯和0.6g丙烯酸乙酯与异丁烯酸的共聚物(1∶1)(KollicoatMAE,BASF AG)在36g异丙醇内的溶液中,获得了浑浊悬浮液。
为了将利托那韦与Kollicoat转化成分子分散体形式,将该粗分散体与120g水在200℃的混合温度下混合0.3秒。为了沉淀出胶体形式的利托那韦与Kollicoat,将该分子分散溶液进料到另一混合室中。将其与4.3g明胶A100和6.5g乳糖在去离子水中的、已经用1N NaOH调节至pH=9.0的490g水溶液于25℃混合。该加工过程中的压力限制在30巴。混合后,获得了具有浑浊淡黄色的利托那韦胶态分散体。
使用准弹性光散射来测定平均粒径,测得的平均粒径为260nm(方差为42%)。在一小时期间平均粒径仅增加了20nm,即增加至280nm。对于不使用Kollicoat以类似方法制得的利托那韦胶态分散体,其在一小时期间平均粒径增加了400nm。这些结果总结在表1中。
表1
制备胶态分散体后的时间 | 含Kollicoat的胶态分散体 | 不含Kollicoat的胶态分散体 |
3分钟 | 260nm | 410nm |
15分钟 | 259nm | 485nm |
30分钟 | 258nm | 671nm |
60分钟 | 281nm | 835nm |
b)将分散体a)干燥以获得纳米颗粒干燥粉末
将产物1a)喷雾干燥,获得了纳米颗粒干燥粉末。通过色谱法测得该粉末中的活性成分含量为19.84%(重量)。将干粉溶于饮用水中,以形成平均粒径为306nm(方差为48%)的浑浊黄色分散体(水溶胶)。在一小时期间平均粒径仅增加了约30nm,即增加至349nm。对于不使用Kollicoat以类似方法制得的利托那韦胶态分散体,其在一小时期间平均粒径增加了约350nm。这些结果总结在表2中。
表2
制备胶态分散体后的时间 | 含Kollicoat的胶态分散体 | 不含Kollicoat的胶态分散体 |
3分钟 | 306nm | 585nm |
15分钟 | 307nm | 726nm |
30分钟 | 324nm | 815nm |
60分钟 | 349nm | 938nm |
c)宽角X-射线散射
附图1描述了活性成分(上面)和1b)所得干粉(下面)的散射图。正如X-射线图所证实的那样,利托那韦原料是晶体,其特征是有很多尖锐干扰峰。与之相反,干粉的散射图仅表现出扩散的、宽的干扰峰,这正是非晶形材料的典型特征。因此,在1b)制得的干粉中的活性成分呈X-射线非晶形形式。这同样适用于辅料乳糖和棕榈酸抗坏血酸酯(否则这两种成分是晶体形式)。
制剂实施例2
活性成分含量为大约20%重量的环孢菌素干粉的制备
a)制备微粉
在25℃,将3g环孢菌素搅拌到0.6g棕榈酸抗坏血酸酯和0.6g KollicoatMAE(BASF AG)在36g异丙醇内的溶液中,获得了轻度浑浊悬浮液。
为了将环孢菌素A与Kollicoat转化成分子分散体形式,将该粗分散体与120g水在200℃的混合温度下混合0.3秒。为了沉淀出胶体形式的环孢菌素与Kollicoat,将该分子分散溶液进料到另一混合室中。将其与4.3g明胶A100和6.5g乳糖在去离子水中的、已经用1N NaOH调节至pH=9.0的490g水溶液于25℃混合。该加工过程中的压力限制在30巴。混合后,获得了具有浑浊白色的环孢菌素胶态分散体。
使用准弹性光散射来测定平均粒径,测得的平均粒径为249nm(方差为42%)。在一小时期间,在测量的准确度内平均粒径没有任何增加。对于不使用Kollicoat以类似方法制得的环孢菌素胶态分散体,其在一小时期间平均粒径增加了250nm。这些结果总结在表3中。
表3
制备胶态分散体后的时间 | 含Kollicoat的胶态分散体 | 不含Kollicoat的胶态分散体 |
3分钟 | 249nm | 330nm |
15分钟 | 257nm | 364nm |
30分钟 | 251nm | 410nm |
60分钟 | 248nm | 580nm |
b)将分散体a)干燥以获得纳米颗粒干燥粉末
将产物2a)喷雾干燥,获得了纳米颗粒干燥粉末。通过色谱法测得该粉末中的活性成分含量为20.03%(重量)。将干粉溶于饮用水中,以形成平均粒径为263nm(方差为48%)的浑浊白色分散体(水溶胶)。在一小时期间,在测量的准确度内平均粒径没有任何增加。对于不使用Kollicoat以类似方法制得的环孢菌素胶态分散体,其在一小时期间粒径增加了约150nm。这些结果总结在表4中。
表4
制备胶态分散体后的时间 | 含Kollicoat的胶态分散体 | 不含Kollicoat的胶态分散体 |
3分钟 | 263nm | 435nm |
15分钟 | 259nm | 463nm |
30分钟 | 264nm | 518nm |
60分钟 | 267nm | 575nm |
制剂实施例3
按照类似于实施例1的方法,制备含有普罗帕酮作为活性组分的微粉。
制剂实施例4
按照类似于实施例2的方法,制备含有聚合物聚(D,L-丙交酯-共聚-乙交酯)(49mol%D,L-丙交酯,51mol%乙交酯)以代替聚合物KollicoatMAE的微粉。
制剂实施例5
活性成分含量为大约5%的斑蝥黄干粉的制备
a)制备微粉
在25℃,将15g斑蝥黄搅拌到6g乙氧喹和45g Kollicoat MAE在400g四氢呋喃内的溶液中,获得了浑浊悬浮液。
为了将斑蝥黄转化成分子分散体形式,将该粗分散体经由热交换器以1.8kg/h的流速泵送,由此加热至161.5℃。为了沉淀出胶体形式的斑蝥黄与Kollicoat,达到161.5℃之后1.4秒,将该分子分散溶液进料到另一混合室中。将其与30g明胶B200和25g蔗糖在去离子水中的、已经用1N NaOH调节至pH=11.8的9600g水溶液于25℃混合。该加工过程中的压力限制在60巴。混合后,获得了具有浑浊微红色的斑蝥黄胶态分散体。
使用准弹性光散射来测定平均粒径,测得的平均粒径为796nm(方差为81%)。
b)将分散体a)干燥以获得纳米颗粒干粉
在旋转蒸发仪中处理,然后将1a)产物喷雾干燥,获得了纳米颗粒干粉。通过UV/VIS光谱法测得该粉末中的活性成分含量为5.75%重量。将干粉溶于pH值>7的水中,以形成平均粒径为722nm(方差为43%)的浑浊微红色分散体(水溶胶)。
制剂实施例6
活性成分含量为大约25%的虾青素干粉的制备
a)制备微粉
在25℃,将1g虾青素搅拌到3g异丁烯酸/异丁烯酸甲酯共聚物(比例1∶1)(Eudragit L 100,Rhm GmbH)在200g四氢呋喃内的溶液中。为了将虾青素转化成分子分散体形式,将该分散体经由热交换器以1.8kg/h的流速泵送,由此加热至73℃的温度。为了沉淀出胶体形式的虾青素与Eudragit L 100,将该分子分散溶液进料到另一混合室中。将其与10000g去离子水在25℃混合。该加工过程中的压力限制在30巴。混合后,获得了微红色的虾青素胶态分散体。
使用准弹性光散射来测定平均粒径,测得的平均粒径为256nm(方差为56%)。
b)将分散体a)干燥以获得纳米颗粒干粉
在旋转蒸发仪中处理,然后将1a)产物喷雾干燥,获得了纳米颗粒干粉。通过UV/VIS光谱法测得该粉末中的活性成分含量为24.3%重量。将干粉溶于碱性水中,以形成平均粒径为273nm(方差为53%)的红色分散体(水溶胶)。
制剂实施例7
活性成分含量为大约25%的虾青素干粉的制备
a)制备微粉
在25℃,将2g虾青素搅拌到6g Eudragit L 100(Rhm GmbH)在200g四氢呋喃内的溶液中。为了将虾青素转化成分子分散体形式,将该分散体经由热交换器以2.0kg/h的流速泵送,由此加热至73℃的温度。为了沉淀出胶体形式的虾青素与Eudragit L 100,将该分子分散溶液进料到另一混合室中。将其与10000g去离子水在25℃混合。该加工过程中的压力限制在30巴。混合后,获得了微红色的虾青素胶态分散体。
使用准弹性光散射来测定平均粒径,测得的平均粒径为178nm(方差为22%)。
b)将分散体a)干燥以获得纳米颗粒干粉
在旋转蒸发仪中处理,然后将1a)产物喷雾干燥,获得了纳米颗粒干粉。通过UV/VIS光谱法测得该粉末中的活性成分含量为22.7%重量。将干粉溶于碱性水中,以形成平均粒径为175nm(方差为25%)的浑浊微红色分散体(水溶胶)。
本发明纳米颗粒可用于例如制备下述剂型:
1.片剂
将10%重量纳米颗粒制剂(以乳糖作载体)与10%重量蔗糖、28%重量微晶纤维素、3%重量Kollidon VA 64和0.2%重量Aerosil混合,然后直接压制成片。片剂重量为250mg。直径为8mm。硬度为150N,在水中的崩解度为13分钟。
2.贴剂
制备具有由17.5%重量聚苯乙烯和17.5%重量聚乙酸乙烯酯以及30%重量本发明纳米颗粒组成的贮药库的贴剂。
3.水包油霜剂
将24g液体石蜡、5g Cremophor S 9(聚乙二醇硬脂酸酯)、6g蜂蜡、2g Cutina CP(棕榈酸鲸蜡基酯)、3g甘油和60g水形成霜剂基质,将20g本发明纳米颗粒制剂搅拌到该霜剂基质中。
对于生产,将Cremophor溶于该液相中,将该混合物与水在剧烈搅拌下混合。继续搅拌直至冷却,然后加入纳米颗粒制剂,并均化。
4.局部施用制剂
如下所述获得具有纳米颗粒核芯/壳制剂的局部施用制剂:(g/100g)
在80℃将0.14g对羟基苯甲酸甲酯与0.1g对羟基苯甲酸丙酯以及0.1g EDTA二水合物溶于78.42g水中。冷却至约30℃后,加入粉末形式的20g本发明纳米颗粒,并通过搅拌均化。然后加入0.8g Carbomer 934P和0.44g NaOH。
5.凝胶剂
聚乙二醇20g、泊咯沙姆1885g、泊咯沙姆407 22g、NaCl 1g、水51g、实施例1微粉20g。
6.滴眼剂
10g实施例1微粉、14g Kollidon K 25、防腐剂(按需要)、水加至100g。
7.气雾剂
如下所述制备粉末制剂:
向含有75mg布地奈德的纳米颗粒制剂的含水胶态悬浮液中加入1400g乳糖。然后将该混合物喷雾干燥。所得粉末的粒径为7μm,水分含量为0.8%重量。
具有推进剂的制剂:
将0.25%重量纳米颗粒布地奈德制剂与4%重量乙醇和水混合物(50∶50)以及95.75%重量1,1,1,2-四氟乙烷置于在压力下的铝容器中。
8.硬膏剂
将7%重量甘油加到6%重量聚丙烯酸和5%重量聚丙烯酸钠以及0.5%重量Aerosil 200的混合物中。通过搅拌将该混合物均化。然后将该混合物加到0.03%重量EDTA在65%重量水中的溶液中。向所得混合物中再加入0.3%重量聚氧化乙烯脱水山梨醇一硬脂酸酯,并加热至50℃。最后,将本发明纳米颗粒粉末搅拌到该混合物中,把所得组合物涂敷在非纺织硬膏剂基质上。
9.可注射贮药库凝胶剂
10%重量本发明纳米颗粒、30%重量乳酸/乙二醇共聚物、10%重量乙醇、50%重量等渗盐水。
10.泡腾片
217g 制剂实施例3所得普罗帕酮微粉
200g 碳酸氢钾
205.7g 柠檬酸
142.1g 新产(instant)糖
32.0g Macrogol 200
2g 柠檬香料
1.2g 糖精
将该混合物在常规条件下压制成厚5.9mm、且重2.9g的片剂。在水中的崩解度(烧杯):9分钟。
Claims (5)
1.一种生产具有核芯/壳结构的药物或化妆品活性成分的纳米颗粒制剂的方法,其中X-射线非晶型活性成分与丙烯酸乙酯和甲基丙烯酸的共聚物存在于核芯中,并且壳由稳定包衣基质组成,所述的稳定包衣基质由明胶、酪蛋白或酪蛋白酸钠组成,其中活性成分在25℃在水中的溶解度低于10mg/ml。
2.权利要求1的方法,其中所述核芯/壳结构具有0.05-0.9μm的平均粒径。
3.权利要求1的方法,其中所述的纳米颗粒制剂是制剂的水溶胶。
4.权利要求1的方法,该方法包含制备活性成分在能与水达到至少10%重量混溶的有机溶剂中的溶液,将该溶液与核芯聚合物或者核芯聚合物在有机溶剂中的溶液混合,将所得混合物与包衣聚合物的水溶液接触。
5.权利要求4的方法,其中在将活性成分溶液与核芯聚合物溶液混合时发生核芯颗粒沉淀。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19856432.5 | 1998-12-08 | ||
DE19856432A DE19856432A1 (de) | 1998-12-08 | 1998-12-08 | Nanopartikuläre Kern-Schale Systeme sowie deren Verwendung in pharmazeutischen und kosmetischen Zubereitungen |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1334724A CN1334724A (zh) | 2002-02-06 |
CN100346775C true CN100346775C (zh) | 2007-11-07 |
Family
ID=7890273
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998160784A Expired - Lifetime CN100346775C (zh) | 1998-12-08 | 1999-12-07 | 纳米颗粒核芯-壳系统及其在药物和化妆品制剂中的应用 |
Country Status (7)
Country | Link |
---|---|
US (1) | US7687071B1 (zh) |
EP (1) | EP1137404A2 (zh) |
JP (1) | JP2002531492A (zh) |
CN (1) | CN100346775C (zh) |
CA (1) | CA2353809A1 (zh) |
DE (1) | DE19856432A1 (zh) |
WO (1) | WO2000033820A2 (zh) |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY145265A (en) * | 1998-07-20 | 2012-01-13 | Abbott Lab | Amorphous ritonavir |
US6471951B1 (en) * | 1999-04-30 | 2002-10-29 | Color Access, Inc. | Eyebrow pencil with agglomerated pigments |
GB9911037D0 (en) * | 1999-05-13 | 1999-07-14 | Micap Limited | Nicotine delivery service |
DE10026698A1 (de) * | 2000-05-30 | 2001-12-06 | Basf Ag | Selbstemulgierende Wirkstoffformulierung und Verwendung dieser Formulierung |
US8137699B2 (en) | 2002-03-29 | 2012-03-20 | Trustees Of Princeton University | Process and apparatuses for preparing nanoparticle compositions with amphiphilic copolymers and their use |
WO2003043586A2 (en) * | 2001-11-20 | 2003-05-30 | Advanced Inhalation Research, Inc. | Compositions for sustained action product delivery |
GB0216700D0 (en) | 2002-07-18 | 2002-08-28 | Astrazeneca Ab | Process |
DE10240956B4 (de) * | 2002-09-05 | 2005-03-17 | Christian-Albrechts-Universität Zu Kiel | Heterogene Kern-Schale Mikrogele mit mehrstufigem Schaltverhalten |
DE10248619A1 (de) * | 2002-10-18 | 2004-04-29 | Bayer Ag | Verfahren zur Herstellung pulverförmiger Wirkstoff-Formulierungen mit kompressiblen Fluiden |
GB0302673D0 (en) | 2003-02-06 | 2003-03-12 | Astrazeneca Ab | Pharmaceutical formulations |
US8377952B2 (en) * | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
DE10350528A1 (de) * | 2003-10-29 | 2005-06-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Arzneimittelformulierung, enthaltend einen LTB4-Antagonisten, sowie Verfahren zu deren Herstellung und deren Verwendung |
DE10351087A1 (de) * | 2003-10-31 | 2005-05-25 | Bayer Technology Services Gmbh | Feste Wirkstoff-Formulierung |
DE10355400A1 (de) | 2003-11-25 | 2005-07-07 | Noack, Andreas, Dr. | Multikomponenten Mineralstoffpräparate und Verfahren zur Herstellung von Multikomponenten-Mineralstoffpräparaten |
EP1750669A1 (en) * | 2004-05-04 | 2007-02-14 | Boehringer Ingelheim International Gmbh | Solid pharmaceutical form comprising an ltb4 antagonist |
WO2006062740A2 (en) * | 2004-11-22 | 2006-06-15 | Nu-Tein Co., Inc. | Topical skin patch containing xanthophylls |
US20110177306A1 (en) * | 2004-12-17 | 2011-07-21 | Mitsubishi Chemical Corporation | Novel Core-Shell Structure |
DE102005026755A1 (de) * | 2005-06-09 | 2006-12-14 | Basf Ag | Herstellung von festen Lösungen schwerlöslicher Wirkstoffe durch Kurzzeitüberhitzung und schnelle Trocknung |
DE102005027333B4 (de) | 2005-06-13 | 2017-04-13 | Terra Nano Ltd. | Nanoskalische Reaktivdesorption - ein Verfahren zur Herstellung kolloidalisierter Wirkstoff- oder Vitalstoffspezies, insbesondere entsprechender Wirkstoff- oder Vitalstoffkonzentraten sowie Vorrichtungen zur Durchführung derselben |
ZA200802765B (en) | 2005-08-31 | 2009-08-26 | Abraxis Bioscience Llc | Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents |
EP1942728A1 (de) * | 2005-10-27 | 2008-07-16 | Basf Se | Agrochemische nanopartikuläre wirkstoffformulierungen |
CA2625861A1 (en) * | 2005-10-27 | 2007-05-03 | Basf Se | Nanoparticulate active ingredient formulations |
US8231907B2 (en) | 2006-03-21 | 2012-07-31 | Morehouse School Of Medicine | Nanoparticles for delivery of active agents |
US8257685B2 (en) * | 2006-04-04 | 2012-09-04 | Stc.Unm | Swellable particles for drug delivery |
US20080299210A1 (en) * | 2006-04-13 | 2008-12-04 | Min Wei | Stable nanosized amorphous drug |
JP5578655B2 (ja) * | 2007-03-02 | 2014-08-27 | ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ イリノイ | 微粒子による薬物送達 |
MX2010014018A (es) | 2008-06-16 | 2011-06-21 | Bind Biosciences Inc | Nanopartículas poliméricas cargadas con fármaco y métodos de preparación y uso de las mismas. |
US8318211B2 (en) | 2008-06-16 | 2012-11-27 | Bind Biosciences, Inc. | Therapeutic polymeric nanoparticles comprising vinca alkaloids and methods of making and using same |
WO2010005726A2 (en) | 2008-06-16 | 2010-01-14 | Bind Biosciences Inc. | Therapeutic polymeric nanoparticles with mtor inhibitors and methods of making and using same |
WO2010075072A2 (en) | 2008-12-15 | 2010-07-01 | Bind Biosciences | Long circulating nanoparticles for sustained release of therapeutic agents |
US8685538B2 (en) | 2009-03-25 | 2014-04-01 | Northeastern University | Stable polyelectrolyte coated nanoparticles |
EP2421517A4 (en) * | 2009-04-23 | 2013-08-07 | Sustained Nano Systems Llc | DONATION DEVICE WITH CONTROLLED OUTPUT |
WO2011023446A1 (en) * | 2009-08-31 | 2011-03-03 | Technische Universität Graz | Sensitive paints |
US9775819B2 (en) * | 2009-09-16 | 2017-10-03 | R.P. Scherer Technologies, Llc | Oral solid dosage form containing nanoparticles and process of formulating the same using fish gelatin |
EA036522B1 (ru) | 2009-12-11 | 2020-11-19 | Пфайзер Инк. | Фармацевтическая композиция, пригодная для лиофилизации, содержащая множество терапевтических частиц |
JP5965844B2 (ja) | 2009-12-15 | 2016-08-10 | バインド セラピューティックス インコーポレイテッド | 高いガラス転移温度または高分子量のコポリマーを有する治療用ポリマーナノ粒子組成物 |
EP2512487A4 (en) * | 2009-12-15 | 2013-08-07 | THERAPEUTIC POLYMERNANOPARTICLES WITH CORTICOSTEROIDS AND METHOD FOR THE PRODUCTION AND USE THEREOF | |
WO2012140181A1 (de) | 2011-04-15 | 2012-10-18 | Basf Se | Verfahren zur herstellung wässriger dispersionen aliphatischer polycarbonate |
CN102406941B (zh) * | 2011-07-29 | 2015-03-11 | 沈阳药科大学 | 含有改性明胶肽的纳米化难溶性活性组分及其制备方法 |
GB201115635D0 (en) | 2011-09-09 | 2011-10-26 | Univ Liverpool | Compositions of lopinavir and ritonavir |
WO2014043618A1 (en) | 2012-09-17 | 2014-03-20 | Bind Therapeutics, Inc. | Process for preparing therapeutic nanoparticles |
SG10201706968UA (en) * | 2013-02-05 | 2017-09-28 | 1Globe Health Inst Llc | Biodegradable and clinically-compatible nanoparticles as drug delivery carriers |
HUE043964T2 (hu) | 2014-03-14 | 2019-09-30 | Pfizer | Terápiás szert tartalmazó terápiás nanorészecskék és eljárás ezek elõállítására és alkalmazására |
JP6660372B2 (ja) * | 2014-08-07 | 2020-03-11 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | 送達システム |
CN105640819A (zh) * | 2014-11-13 | 2016-06-08 | 广州十长生化妆品有限公司 | 一种具有嫩滑美白肌肤的去角质微球及其应用 |
IL271908B2 (en) | 2017-07-11 | 2024-02-01 | Sustained Nano Systems Llc | Over-compressed pharmaceutical preparations |
CA3069155A1 (en) | 2017-07-11 | 2019-01-17 | Sustained Nano Systems Llc | Radiation sterilization of hypercompressed polymer dosage forms |
JP7378393B2 (ja) * | 2017-11-10 | 2023-11-13 | オースティンピーエックス リミテッド ライアビリティ カンパニー | 改善された薬物製剤 |
WO2019226571A1 (en) * | 2018-05-19 | 2019-11-28 | Gary Binyamin | Foam formulations and delivery methods to the body |
EP3804701A1 (de) * | 2019-10-10 | 2021-04-14 | Bayer AG | Verfahren zur herstellung einer pharmazeutischen formulierung mit kristallinen und amorphen anteilen eines wirkstoffes |
CA3208608A1 (en) * | 2021-02-12 | 2022-08-18 | Ephemeral Solutions, Inc. | Particles containing coloring agents and methods of using the same |
CN116459231B (zh) * | 2023-05-23 | 2023-09-08 | 中国农业大学 | 一种温敏载药核壳纳米颗粒的制备及应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3742473A1 (de) * | 1986-12-19 | 1988-07-28 | Sandoz Ag | Hydrosole von pharmakologischen wirkstoffen und deren pharmazeutischen kompositionen |
US5133908A (en) * | 1986-12-31 | 1992-07-28 | Centre National De La Recherche Scientifique (Cnrs) | Process for the preparation of dispersible colloidal systems of a substance in the form of nanoparticles |
WO1993025221A1 (en) * | 1992-06-11 | 1993-12-23 | Alkermes Controlled Therapeutics, Inc. | Erythropoietin drug delivery system |
WO1995005165A1 (en) * | 1993-08-13 | 1995-02-23 | Bayer Corporation | Hydrolyzed gelatin as a flavor enhancer in a chewable tablet |
WO1998014174A1 (en) * | 1996-10-01 | 1998-04-09 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1282405C (en) | 1984-05-21 | 1991-04-02 | Michael R. Violante | Method for making uniformly sized particles from water-insoluble organic compounds |
US4826689A (en) | 1984-05-21 | 1989-05-02 | University Of Rochester | Method for making uniformly sized particles from water-insoluble organic compounds |
FR2608988B1 (fr) | 1986-12-31 | 1991-01-11 | Centre Nat Rech Scient | Procede de preparation de systemes colloidaux dispersibles d'une substance, sous forme de nanoparticules |
DE3702029A1 (de) | 1987-01-24 | 1988-08-04 | Basf Ag | Waessriges oder pulverfoermiges, wasserdispergierbares praeparat eines in wasser schwerloeslichen pharmazeutischen wirkstoffs und verfahren zu seiner herstellung |
DE3936053A1 (de) | 1989-10-28 | 1991-05-02 | Basf Ag | Verfahren zur verbesserung der bioverfuegbarkeit von pharmazeutischen wirkstoffen mit peptidbindungen |
US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
DE4131562A1 (de) | 1991-09-18 | 1993-03-25 | Medac Klinische Spezialpraep | Arzneistofftraeger aus festen lipidteilchen-feste lipidnanosphaeren (sln) |
DE4327063A1 (de) | 1993-08-12 | 1995-02-16 | Kirsten Dr Westesen | Ubidecarenon-Partikel mit modifizierten physikochemischen Eigenschaften |
DE59409568D1 (de) * | 1993-09-09 | 2000-11-30 | Schering Ag | Wirkstoffe und gas enthaltende mikropartikel |
DE4414755C2 (de) * | 1994-04-27 | 2000-11-16 | Lohmann Therapie Syst Lts | Kollagenzubereitung zur gesteuerten Abgabe von Wirkstoffen, Verfahren und Verwendung |
ES2078190B1 (es) * | 1994-05-20 | 1996-08-01 | Cusi Lab | Procedimiento para el recubrimiento de goticulas o particulas de tamaño nanometrico. |
DE4440337A1 (de) | 1994-11-11 | 1996-05-15 | Dds Drug Delivery Services Ges | Pharmazeutische Nanosuspensionen zur Arzneistoffapplikation als Systeme mit erhöhter Sättigungslöslichkeit und Lösungsgeschwindigkeit |
JP5038552B2 (ja) | 1995-10-17 | 2012-10-03 | オバン・エナジー・リミテッド | 不溶性薬物の送達 |
US5891474A (en) * | 1997-01-29 | 1999-04-06 | Poli Industria Chimica, S.P.A. | Time-specific controlled release dosage formulations and method of preparing same |
US6045829A (en) * | 1997-02-13 | 2000-04-04 | Elan Pharma International Limited | Nanocrystalline formulations of human immunodeficiency virus (HIV) protease inhibitors using cellulosic surface stabilizers |
-
1998
- 1998-12-08 DE DE19856432A patent/DE19856432A1/de not_active Withdrawn
-
1999
- 1999-12-07 US US09/857,480 patent/US7687071B1/en not_active Expired - Fee Related
- 1999-12-07 JP JP2000586313A patent/JP2002531492A/ja not_active Withdrawn
- 1999-12-07 WO PCT/EP1999/009545 patent/WO2000033820A2/de not_active Application Discontinuation
- 1999-12-07 EP EP99963399A patent/EP1137404A2/de not_active Ceased
- 1999-12-07 CN CNB998160784A patent/CN100346775C/zh not_active Expired - Lifetime
- 1999-12-07 CA CA002353809A patent/CA2353809A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3742473A1 (de) * | 1986-12-19 | 1988-07-28 | Sandoz Ag | Hydrosole von pharmakologischen wirkstoffen und deren pharmazeutischen kompositionen |
US5133908A (en) * | 1986-12-31 | 1992-07-28 | Centre National De La Recherche Scientifique (Cnrs) | Process for the preparation of dispersible colloidal systems of a substance in the form of nanoparticles |
WO1993025221A1 (en) * | 1992-06-11 | 1993-12-23 | Alkermes Controlled Therapeutics, Inc. | Erythropoietin drug delivery system |
WO1995005165A1 (en) * | 1993-08-13 | 1995-02-23 | Bayer Corporation | Hydrolyzed gelatin as a flavor enhancer in a chewable tablet |
WO1998014174A1 (en) * | 1996-10-01 | 1998-04-09 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
Also Published As
Publication number | Publication date |
---|---|
WO2000033820A3 (de) | 2000-10-12 |
JP2002531492A (ja) | 2002-09-24 |
US7687071B1 (en) | 2010-03-30 |
WO2000033820A2 (de) | 2000-06-15 |
CN1334724A (zh) | 2002-02-06 |
EP1137404A2 (de) | 2001-10-04 |
DE19856432A1 (de) | 2000-06-15 |
CA2353809A1 (en) | 2000-06-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100346775C (zh) | 纳米颗粒核芯-壳系统及其在药物和化妆品制剂中的应用 | |
TWI342221B (en) | Solid pharmaceutical dosage form | |
JP5439366B2 (ja) | 偏析防止効果に優れるセルロース粉末及びその組成物 | |
TWI354568B (en) | Insoluble drug particle compositions with improved | |
JP5759457B2 (ja) | セルロースと無機化合物を含む複合粒子 | |
CN100462066C (zh) | 药剂的新制剂及其制备和应用方法 | |
JP2010047579A (ja) | セルロース系表面安定剤を用いたヒト免疫不全ウイルス(hiv)プロテアーゼ阻害剤のナノ結晶製剤及びそのような製剤の製造方法 | |
CN101031285A (zh) | 含有微粒的组合物及其制备方法 | |
CN102740836A (zh) | 用于制备商品化纳米颗粒和微粒粉末的方法 | |
CN102740835A (zh) | 包封的纳米颗粒在工业规模的制备 | |
CN1688291A (zh) | 含有固体药物分散体的即刻释放剂型 | |
CN105246598A (zh) | 乙酸阿比特龙酯制剂 | |
TW201043264A (en) | Reduction of flake-like aggregation in nanoparticulate active agent compositions | |
JP2001511156A (ja) | 高いバイオアベイラビリティーを有するフェノフィブレート医薬組成物及びそれを調製するための方法 | |
CN1917859A (zh) | 载药纳米微粒及其制备方法以及含有该纳米微粒的非肠道给药用制剂 | |
JPWO2005013938A1 (ja) | 薬物超微粒子の製造法及び製造装置 | |
CN106687112A (zh) | 醋酸阿比特龙制剂和使用方法 | |
CN1298312C (zh) | 物质微粒的制备方法、物质微粒及其药物组合物 | |
JP2021169504A (ja) | アプレピタント経口液体製剤 | |
CN102793706B (zh) | 托伐普坦固体分散体的制备方法 | |
JPWO2006073154A1 (ja) | 医薬組成物及びその製造方法 | |
CN106794251A (zh) | 阿立哌唑前体药物组合物 | |
TWI729476B (zh) | 纖維素粉末、其用途及錠劑 | |
TWI724534B (zh) | 纖維素粉末、錠劑及錠劑之製造方法 | |
JP3103513B2 (ja) | サメ軟骨経口摂取製剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
C10 | Entry into substantive examination | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term | ||
CX01 | Expiry of patent term |
Granted publication date: 20071107 |