CA2442479C - Compositions topiques d'apport de prostaglandine e1 - Google Patents

Compositions topiques d'apport de prostaglandine e1 Download PDF

Info

Publication number: CA2442479C
Authority: CA; Canada
Prior art keywords: accordance; prostaglandin; composition; group; alkyl
Prior art date: 1999-05-13
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

Application number

CA002442479A

Other languages

English (en)

Other versions

CA2442479A1 (fr

Inventor

James L. Yeager

Nadir Buyuktimkin

Servet Buyuktimkin

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Ferring International Center SA

Original Assignee

Nexmed Holdings Inc

Priority date (The priority date 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 date listed.)

1999-05-13

Filing date

1999-05-13

Publication date

2005-12-13

1999-05-13 Application filed by Nexmed Holdings Inc filed Critical Nexmed Holdings Inc

1999-05-13 Priority claimed from CA002373821A external-priority patent/CA2373821C/fr

2000-11-23 Publication of CA2442479A1 publication Critical patent/CA2442479A1/fr

2005-12-13 Application granted granted Critical

2005-12-13 Publication of CA2442479C publication Critical patent/CA2442479C/fr

2019-05-13 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 144
GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 title claims abstract description 39
229960000711 alprostadil Drugs 0.000 title claims abstract description 39
GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 title claims abstract description 38
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 title claims abstract description 36
230000000699 topical effect Effects 0.000 title claims abstract description 36
150000002148 esters Chemical class 0.000 claims abstract description 20
239000003961 penetration enhancing agent Substances 0.000 claims abstract description 20
150000002634 lipophilic molecules Chemical class 0.000 claims abstract description 19
239000007853 buffer solution Substances 0.000 claims abstract description 18
229920001282 polysaccharide Polymers 0.000 claims abstract description 17
150000004676 glycans Chemical class 0.000 claims abstract description 16
239000005017 polysaccharide Substances 0.000 claims abstract description 16
125000001931 aliphatic group Chemical group 0.000 claims abstract description 9
230000002378 acidificating effect Effects 0.000 claims abstract description 7
KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 claims abstract 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 46
-1 N,N-disubstituted amino Chemical group 0.000 claims description 28
MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 claims description 18
229920002125 Sokalan® Polymers 0.000 claims description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
239000003995 emulsifying agent Substances 0.000 claims description 12
208000012322 Raynaud phenomenon Diseases 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229920000161 Locust bean gum Polymers 0.000 claims description 9
235000010420 locust bean gum Nutrition 0.000 claims description 9
239000000711 locust bean gum Substances 0.000 claims description 9
229920000926 Galactomannan Polymers 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 8
OMDQUFIYNPYJFM-XKDAHURESA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-[[(2r,3s,4r,5s,6r)-4,5,6-trihydroxy-3-[(2s,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 claims description 7
206010040882 skin lesion Diseases 0.000 claims description 7
231100000444 skin lesion Toxicity 0.000 claims description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
208000001034 Frostbite Diseases 0.000 claims description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
SZYSLWCAWVWFLT-UTGHZIEOSA-N [(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxolan-2-yl]methyl octadecanoate Chemical group O([C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@]1(COC(=O)CCCCCCCCCCCCCCCCC)O[C@H](CO)[C@@H](O)[C@@H]1O SZYSLWCAWVWFLT-UTGHZIEOSA-N 0.000 claims description 6
230000035876 healing Effects 0.000 claims description 6
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 5
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 5
201000001320 Atherosclerosis Diseases 0.000 claims description 5
208000003782 Raynaud disease Diseases 0.000 claims description 5
206010043540 Thromboangiitis obliterans Diseases 0.000 claims description 5
HSMMSDWNEJLVRY-INIZCTEOSA-N dodecyl (2s)-2-(dimethylamino)propanoate Chemical compound CCCCCCCCCCCCOC(=O)[C@H](C)N(C)C HSMMSDWNEJLVRY-INIZCTEOSA-N 0.000 claims description 5
208000015181 infectious disease Diseases 0.000 claims description 5
230000002757 inflammatory effect Effects 0.000 claims description 5
208000025865 Ulcer Diseases 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
230000002062 proliferating effect Effects 0.000 claims description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
206010024648 Livedo reticularis Diseases 0.000 claims description 3
229930006000 Sucrose Natural products 0.000 claims description 3
206010052428 Wound Diseases 0.000 claims description 3
208000027418 Wounds and injury Diseases 0.000 claims description 3
229960001631 carbomer Drugs 0.000 claims description 3
IHSPMDXQWYKHOA-UHFFFAOYSA-N dodecyl 2-(dimethylamino)acetate Chemical group CCCCCCCCCCCCOC(=O)CN(C)C IHSPMDXQWYKHOA-UHFFFAOYSA-N 0.000 claims description 3
230000002708 enhancing effect Effects 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
239000008213 purified water Substances 0.000 claims description 3
239000005720 sucrose Substances 0.000 claims description 3
231100000397 ulcer Toxicity 0.000 claims description 3
NCXUNZWLEYGQAH-UHFFFAOYSA-N 1-(dimethylamino)propan-2-ol Chemical compound CC(O)CN(C)C NCXUNZWLEYGQAH-UHFFFAOYSA-N 0.000 claims description 2
KTPHASGENPMMQK-UHFFFAOYSA-N 1-(dimethylamino)propan-2-yl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC(C)CN(C)C KTPHASGENPMMQK-UHFFFAOYSA-N 0.000 claims description 2
KIPQYJOLEGBNHQ-UHFFFAOYSA-N 1-(dimethylamino)propan-2-yl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OC(C)CN(C)C KIPQYJOLEGBNHQ-UHFFFAOYSA-N 0.000 claims description 2
208000002874 Acne Vulgaris Diseases 0.000 claims description 2
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
206010012438 Dermatitis atopic Diseases 0.000 claims description 2
229920002907 Guar gum Polymers 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 2
201000004681 Psoriasis Diseases 0.000 claims description 2
206010000496 acne Diseases 0.000 claims description 2
201000008937 atopic dermatitis Diseases 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
239000000665 guar gum Substances 0.000 claims description 2
235000010417 guar gum Nutrition 0.000 claims description 2
229960002154 guar gum Drugs 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
229940017219 methyl propionate Drugs 0.000 claims description 2
229940049964 oleate Drugs 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
229920001223 polyethylene glycol Polymers 0.000 claims description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 3
125000004432 carbon atom Chemical group C* 0.000 claims 2
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
239000002202 Polyethylene glycol Substances 0.000 claims 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims 1
239000007787 solid Substances 0.000 abstract description 12
150000003180 prostaglandins Chemical class 0.000 description 47
230000035515 penetration Effects 0.000 description 31
235000019441 ethanol Nutrition 0.000 description 19
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 17
239000003814 drug Substances 0.000 description 14
239000004615 ingredient Substances 0.000 description 14
229940079593 drug Drugs 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
230000000052 comparative effect Effects 0.000 description 11
239000003623 enhancer Substances 0.000 description 10
210000004027 cell Anatomy 0.000 description 9
230000001965 increasing effect Effects 0.000 description 9
239000008194 pharmaceutical composition Substances 0.000 description 8
125000000217 alkyl group Chemical group 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
238000009472 formulation Methods 0.000 description 7
238000000926 separation method Methods 0.000 description 7
230000002459 sustained effect Effects 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000000872 buffer Substances 0.000 description 6
238000001990 intravenous administration Methods 0.000 description 6
238000000034 method Methods 0.000 description 6
241000270295 Serpentes Species 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
230000001186 cumulative effect Effects 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
239000000243 solution Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
239000000853 adhesive Substances 0.000 description 4
230000001070 adhesive effect Effects 0.000 description 4
230000008901 benefit Effects 0.000 description 4
230000002349 favourable effect Effects 0.000 description 4
238000011068 loading method Methods 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
238000012360 testing method Methods 0.000 description 4
DZUXGQBLFALXCR-UHFFFAOYSA-N (+)-(9alpha,11alpha,13E,15S)-9,11,15-trihydroxyprost-13-en-1-oic acid Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CCCCCCC(O)=O DZUXGQBLFALXCR-UHFFFAOYSA-N 0.000 description 3
AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 3
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
208000018262 Peripheral vascular disease Diseases 0.000 description 3
244000046052 Phaseolus vulgaris Species 0.000 description 3
235000010627 Phaseolus vulgaris Nutrition 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
239000002253 acid Substances 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000000499 gel Substances 0.000 description 3
238000001802 infusion Methods 0.000 description 3
230000003902 lesion Effects 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
230000001185 psoriatic effect Effects 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
208000010228 Erectile Dysfunction Diseases 0.000 description 2
208000005230 Leg Ulcer Diseases 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
206010040047 Sepsis Diseases 0.000 description 2
206010040943 Skin Ulcer Diseases 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000008859 change Effects 0.000 description 2
238000002144 chemical decomposition reaction Methods 0.000 description 2
239000003086 colorant Substances 0.000 description 2
239000006071 cream Substances 0.000 description 2
230000006378 damage Effects 0.000 description 2
238000002716 delivery method Methods 0.000 description 2
238000009792 diffusion process Methods 0.000 description 2
229940113088 dimethylacetamide Drugs 0.000 description 2
201000010099 disease Diseases 0.000 description 2
NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
238000000605 extraction Methods 0.000 description 2
201000001881 impotence Diseases 0.000 description 2
230000006872 improvement Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000000622 irritating effect Effects 0.000 description 2
230000000302 ischemic effect Effects 0.000 description 2
229940074928 isopropyl myristate Drugs 0.000 description 2
230000003908 liver function Effects 0.000 description 2
238000002156 mixing Methods 0.000 description 2
210000004400 mucous membrane Anatomy 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
230000000149 penetrating effect Effects 0.000 description 2
239000004584 polyacrylic acid Substances 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
231100000019 skin ulcer Toxicity 0.000 description 2
150000003431 steroids Chemical class 0.000 description 2
239000000126 substance Substances 0.000 description 2
230000008093 supporting effect Effects 0.000 description 2
230000037317 transdermal delivery Effects 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
230000029663 wound healing Effects 0.000 description 2
VTCLFBZXKIZNKS-UHFFFAOYSA-N 2,6-diamino-5-iminopyrimidin-4-one Chemical compound NC1=NC(=O)C(=N)C(N)=N1 VTCLFBZXKIZNKS-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
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
208000031104 Arterial Occlusive disease Diseases 0.000 description 1
208000033386 Buerger disease Diseases 0.000 description 1
240000008886 Ceratonia siliqua Species 0.000 description 1
208000027932 Collagen disease Diseases 0.000 description 1
206010011703 Cyanosis Diseases 0.000 description 1
125000003423 D-mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
201000003066 Diffuse Scleroderma Diseases 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
206010061126 Escherichia infection Diseases 0.000 description 1
206010057671 Female sexual dysfunction Diseases 0.000 description 1
206010017711 Gangrene Diseases 0.000 description 1
235000017367 Guainella Nutrition 0.000 description 1
229920000569 Gum karaya Polymers 0.000 description 1
206010019799 Hepatitis viral Diseases 0.000 description 1
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
206010067125 Liver injury Diseases 0.000 description 1
CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
241000551546 Minerva Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
MMOXZBCLCQITDF-UHFFFAOYSA-N N,N-diethyl-m-toluamide Chemical compound CCN(CC)C(=O)C1=CC=CC(C)=C1 MMOXZBCLCQITDF-UHFFFAOYSA-N 0.000 description 1
241000906034 Orthops Species 0.000 description 1
208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
229920002367 Polyisobutene Polymers 0.000 description 1
239000004721 Polyphenylene oxide Substances 0.000 description 1
241000286862 Siliqua Species 0.000 description 1
206010040880 Skin irritation Diseases 0.000 description 1
241000934878 Sterculia Species 0.000 description 1
101100115801 Streptomyces mobaraensis daip gene Proteins 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
201000009594 Systemic Scleroderma Diseases 0.000 description 1
206010042953 Systemic sclerosis Diseases 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
244000269722 Thea sinensis Species 0.000 description 1
206010047642 Vitiligo Diseases 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000008272 agar Substances 0.000 description 1
238000013019 agitation Methods 0.000 description 1
125000005250 alkyl acrylate group Chemical group 0.000 description 1
208000004631 alopecia areata Diseases 0.000 description 1
230000003872 anastomosis Effects 0.000 description 1
239000000420 anogeissus latifolia wall. gum Substances 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
208000021328 arterial occlusion Diseases 0.000 description 1
230000003143 atherosclerotic effect Effects 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
230000009172 bursting Effects 0.000 description 1
CNYFJCCVJNARLE-UHFFFAOYSA-L calcium;2-sulfanylacetic acid;2-sulfidoacetate Chemical compound [Ca+2].[O-]C(=O)CS.[O-]C(=O)CS CNYFJCCVJNARLE-UHFFFAOYSA-L 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
235000010418 carrageenan Nutrition 0.000 description 1
239000000679 carrageenan Substances 0.000 description 1
229920001525 carrageenan Polymers 0.000 description 1
229940113118 carrageenan Drugs 0.000 description 1
229940089960 chloroacetate Drugs 0.000 description 1
JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
230000000112 colonic effect Effects 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
239000002537 cosmetic Substances 0.000 description 1
230000000254 damaging effect Effects 0.000 description 1
230000008021 deposition Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
229960002986 dinoprostone Drugs 0.000 description 1
150000004862 dioxolanes Chemical class 0.000 description 1
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
208000020612 escherichia coli infection Diseases 0.000 description 1
FGBGMOBXVFWPCI-UHFFFAOYSA-N ethyl dodecanoate;tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCC(=O)OCC FGBGMOBXVFWPCI-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000004907 flux Effects 0.000 description 1
235000013305 food Nutrition 0.000 description 1
208000020217 fulminant viral hepatitis Diseases 0.000 description 1
235000019314 gum ghatti Nutrition 0.000 description 1
231100000753 hepatic injury Toxicity 0.000 description 1
KUQWZSZYIQGTHT-UHFFFAOYSA-N hexa-1,5-diene-3,4-diol Chemical compound C=CC(O)C(O)C=C KUQWZSZYIQGTHT-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
230000001976 improved effect Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
235000010494 karaya gum Nutrition 0.000 description 1
239000000231 karaya gum Substances 0.000 description 1
229940039371 karaya gum Drugs 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
229940070765 laurate Drugs 0.000 description 1
239000002502 liposome Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000000463 material Substances 0.000 description 1
239000000178 monomer Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
231100000435 percutaneous penetration Toxicity 0.000 description 1
239000002304 perfume Substances 0.000 description 1
230000003836 peripheral circulation Effects 0.000 description 1
239000012466 permeate Substances 0.000 description 1
230000000144 pharmacologic effect Effects 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
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
DZUXGQBLFALXCR-CDIPTNKSSA-N prostaglandin F1alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1CCCCCCC(O)=O DZUXGQBLFALXCR-CDIPTNKSSA-N 0.000 description 1
WGJJROVFWIXTPA-OALUTQOASA-N prostanoic acid Chemical class CCCCCCCC[C@H]1CCC[C@@H]1CCCCCCC(O)=O WGJJROVFWIXTPA-OALUTQOASA-N 0.000 description 1
229940127293 prostanoid Drugs 0.000 description 1
150000003814 prostanoids Chemical class 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
210000003370 receptor cell Anatomy 0.000 description 1
238000011084 recovery Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000011514 reflex Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
230000001235 sensitizing effect Effects 0.000 description 1
230000036332 sexual response Effects 0.000 description 1
230000036556 skin irritation Effects 0.000 description 1
231100000475 skin irritation Toxicity 0.000 description 1
238000002791 soaking Methods 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
150000003445 sucroses Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000003860 topical agent Substances 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
RMNIZOOYFMNEJJ-UHFFFAOYSA-K tripotassium;phosphate;hydrate Chemical compound O.[K+].[K+].[K+].[O-]P([O-])([O-])=O RMNIZOOYFMNEJJ-UHFFFAOYSA-K 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
238000009827 uniform distribution Methods 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
201000001862 viral hepatitis Diseases 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Dermatology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Oil, Petroleum & Natural Gas (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Medicinal Preparation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002442479A 1999-05-13 1999-05-13 Compositions topiques d'apport de prostaglandine e1 Expired - Lifetime CA2442479C (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA002373821A CA2373821C (fr)	1997-11-05	1999-05-13	Compositions topiques d'apport de prostaglandine e1

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002373821A Division CA2373821C (fr)	1997-11-05	1999-05-13	Compositions topiques d'apport de prostaglandine e1

Publications (2)

Publication Number	Publication Date
CA2442479A1 CA2442479A1 (fr)	2000-11-23
CA2442479C true CA2442479C (fr)	2005-12-13

Family

ID=29410014

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002442479A Expired - Lifetime CA2442479C (fr)	1999-05-13	1999-05-13	Compositions topiques d'apport de prostaglandine e1

Country Status (1)

Country	Link
CA (1)	CA2442479C (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2004227853A1 (en) *	2003-04-02	2004-10-21	Nexmed (Holdings), Inc.	Prostaglandin compositions and their use for the treatment of vasospasm
WO2012139033A1 (fr)	2011-04-07	2012-10-11	Nexmed Holdings, Inc.	Procédés et compositions pour traiter la maladie de raynaud

1999
- 1999-05-13 CA CA002442479A patent/CA2442479C/fr not_active Expired - Lifetime

Also Published As

Publication number	Publication date
CA2442479A1 (fr)	2000-11-23

Legal Events

Date	Code	Title	Description
2003-11-25	EEER	Examination request
2019-07-15	MKEX	Expiry	Effective date: 20190513

Publication	Publication Date	Title
CA2373821C (fr)	2003-10-07	Compositions topiques d'apport de prostaglandine e1
KR100614361B1 (ko)	2006-08-18	남성 발기부전증을 치료하기 위한 프로스타글란딘 조성물및 방법
US11246932B2 (en)	2022-02-15	Prostaglandin compositions and methods for the treatment of vasospasm
KR20040033024A (ko)	2004-04-17	남성 발기부전증을 치료하기 위한 프로스타글란딘 조성물및 방법
NZ576242A (en)	2012-04-27	Stabilized prostaglandin e composition
CA2442479C (fr)	2005-12-13	Compositions topiques d'apport de prostaglandine e1
AU2014201174B2 (en)	2016-04-14	Stabilized prostaglandin e composition