WO2000047211A1 - Short contact treatment of psoriasis with topical retinoids - Google Patents
Short contact treatment of psoriasis with topical retinoids Download PDFInfo
- Publication number
- WO2000047211A1 WO2000047211A1 PCT/US2000/003457 US0003457W WO0047211A1 WO 2000047211 A1 WO2000047211 A1 WO 2000047211A1 US 0003457 W US0003457 W US 0003457W WO 0047211 A1 WO0047211 A1 WO 0047211A1
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- WO
- WIPO (PCT)
- Prior art keywords
- retinoid
- psoriasis
- skin
- retinoids
- topically
- Prior art date
Links
- 201000004681 Psoriasis Diseases 0.000 title claims abstract description 19
- 238000011282 treatment Methods 0.000 title description 16
- 230000000699 topical effect Effects 0.000 title description 7
- 150000004492 retinoid derivatives Chemical class 0.000 claims abstract description 23
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 10
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 22
- 229960001727 tretinoin Drugs 0.000 claims description 21
- OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 claims description 12
- 229960000565 tazarotene Drugs 0.000 claims description 11
- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 claims description 9
- 229960002916 adapalene Drugs 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 description 17
- 229930002330 retinoic acid Natural products 0.000 description 14
- -1 alkyoxy Chemical group 0.000 description 12
- 102000003702 retinoic acid receptors Human genes 0.000 description 10
- 108090000064 retinoic acid receptors Proteins 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 5
- 206010067484 Adverse reaction Diseases 0.000 description 4
- 230000006838 adverse reaction Effects 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 150000001241 acetals Chemical class 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 108091027981 Response element Proteins 0.000 description 2
- 102000034527 Retinoid X Receptors Human genes 0.000 description 2
- 108010038912 Retinoid X Receptors Proteins 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229960003471 retinol Drugs 0.000 description 2
- 235000020944 retinol Nutrition 0.000 description 2
- 239000011607 retinol Substances 0.000 description 2
- 125000001444 retinoyl group Chemical group O=C([*])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C1=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C1(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical group C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- DQONDOMCVNYTAV-UHFFFAOYSA-N 6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carbaldehyde Chemical compound C1=C2C(C)(C)CCSC2=CC=C1C#CC1=CC=C(C=O)C=N1 DQONDOMCVNYTAV-UHFFFAOYSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- GJXOBLCKPRMINC-UHFFFAOYSA-N ethyl 5-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 GJXOBLCKPRMINC-UHFFFAOYSA-N 0.000 description 1
- OHBWTWGXPVNMMQ-UHFFFAOYSA-N ethyl 6-[2-(4,4-dimethyl-2,3-dihydrochromen-6-yl)ethynyl]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(OCCC2(C)C)C2=C1 OHBWTWGXPVNMMQ-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 150000004291 polyenes Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000001403 relative X-ray reflectometry Methods 0.000 description 1
- 108091008726 retinoic acid receptors α Proteins 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 229940015347 tazarotene topical gel Drugs 0.000 description 1
- IQIBKLWBVJPOQO-UHFFFAOYSA-N tazarotenic acid Chemical compound C1=C2C(C)(C)CCSC2=CC=C1C#CC1=CC=C(C(O)=O)C=N1 IQIBKLWBVJPOQO-UHFFFAOYSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 150000002266 vitamin A derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; Salts thereof
Definitions
- the present invention is directed to the treatment of psoriasis using topical retinoids.
- the retinoids are a family of compounds including vitamin A, retinoic acid (RA), related derivatives of these, and other compounds capable of binding to retinoic acid receptors (RAR).
- RA which is a natural metabolite of vitamin A
- RAR retinol
- a ⁇ l-trans-RA tretinoin
- RAR- ⁇ , - ⁇ , - ⁇ three identified subtypes of known RAR receptors, respectively termed RAR- ⁇ , - ⁇ , - ⁇ . These receptors, after binding the RA ligand, interact with the promoter region of genes regulated by RA at specific response elements. To bind to the response elements, the RARs heterodimerize with another type of receptor designated as RXR.
- RXRs The natural ligand of RXRs is 9-cts-retinoic acid.
- Many retinoids are known and have been described to date. Generally, retinoids can be identified by their ability to bind RARs, either as all the RARs or selectively to an individual RAR class. Further, retinoids exhibit a diverse spectrum of activities. Among these is use as a topical therapeutic for treatment of skin conditions. There is presently in use an FDA approved treatment for psoriasis employing tazarotene topical gel that is marketed by Allergan, Inc. under the brand name TazoracTM. Moreover, tretinoin, also known by the tradename Retin-ATM, and adapalene are approved for topical use to treat skin conditions.
- TazoracTM gel The mechanism of action in the treatment of psoriasis with tazarotene or other retinoids is not known.
- the current FDA-approved therapeutic regimen requires TazoracTM gel to be applied topically in its 0.05% or its 0.1% formulation and left on the affected skin for long periods of time, e.g. overnight. It is generally applied in the evening and left in place until routine washing in the morning.
- the TazoracTM gel would typically be left on the skin for 8 to 12 hours.
- a major shortcoming of this course of treatment is that adverse skin reactions are experienced by a significant portion of users.
- topically- applied retinoids can be used to treat psoriasis using a short-contact treatment regimen.
- tazarotene has been used for short-contact therapy to treat psoriasis as disclosed in co-pending application entitled “Short Contact Treatment of Psoriasis with Tazarotene Compositions,” filed on the same day as this application by the same inventors and which is hereby incorporated herein by reference.
- the present invention is directed to a method of treating psoriasis in a human patient by topically applying an effective amount of a retinoid composition to the affected area of a patient's skin, allowing that composition to remain in contact with the skin for a period of from about thirty seconds to about thirty minutes, followed by rinsing the composition from the affected area.
- the short contact treatment is performed once a day at least three times a week as long as treatment is needed.
- the active retinoid in the composition is tazarotene, tretinoin or adapalene and, more preferably, is tazarotene.
- short-contact retinoid therapy yields su ⁇ risingly improved and beneficial results in the treatment of psoriasis.
- "Short-contact retinoid therapy” is intended to distinguish over conventional, or extended-contact, treatrhent(s) the retinoid of interest is applied to a patient's skin (typically once a day) and left on the skin indefinitely or until routine washing or showering occurs after a prolonged period of time (typically overnight).
- short-contact retinoid therapy thus comprises the steps of applying a retinoid composition to an affected area of the skin for a brief time period followed by rinsing of the skin / affected area.
- the usual contact time is from about 30 seconds to about 30 minutes, preferably for a period of from about 5 to about 10 minutes.
- the skin is rinsed thoroughly, typically with lukewarm water.
- the short-contact treatments are generally applied to the affected area(s) once or twice a day, preferably once a day, and repeated at least three times a week. If desired or needed, the treatments can be repeated daily. The overall duration of therapy is continued for as long as the conditions exist, i.e., until the plaques are gone or have disappeared, and can readily be determined by the patient's doctor.
- a "retinoid composition” comprises therapeutically-active retinoids, or pharmaceutically- acceptable salts thereof, in admixture with a pharmaceutically acceptable carrier.
- the therapeutically-active retinoids of the invention are selected from the group consisting of a retinoic acid; retinol; therapeutically-active retinoic acid derivatives; therapeutically-active carboxylic acids represented by the formula
- retinoids which are C20 or C22 desmethyl vinylogs of said groups, wherein Z is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group or a cyclohexenyl group, and said phenyl or naphthyl group can be substituted with from 0 to 5 substitutents selected from the group consisting of halo, hydroxy, alkyl, alkyoxy, amino, cyano or carbalkoxy, and wherein double bonds in the polyene chain of any of said groups can have a cis or trans configuration; acetylenic retinoids; adapalene; adapalene derivatives and any compound, natural or synthetic, which possesses the topical biological activity of retinoic acid in the skin and/or the ability to bind to one or more RARs; as well as the geometric isomers and sterioisomers of any of these compounds .
- retinoids contemplated by the invention can be found in U.S. Patent Nos. 4,476,056; 4,105,681; 4,215,215; 4,054,589 and 3,882,244.
- Retinoids include both cis and trans forms having therapeutic activity.
- the retinoids can include a 9-cis double bond, a 13-cis double bond or a ⁇ 3-trans double bond.
- Derivatives of retinoic acid include, but are not limited to, esters, amides, other biologically active forms of retinoic acid such as those with a chemical modification or substitution of a substituent of the molecule, and the like.
- Derivatives of adapalene include, but are not limited to, esters and amides of the naphthoic acid moiety, other biologically active forms of adapalene such as those having a chemical modification or substitution on some part of the molecule while retaining activity, and the like.
- a pharmaceutically acceptable salt may be prepared for any compound of this invention having a functionality capable of forming such salt, for example an acid or amine functionality.
- a pharmaceutically acceptable salt may be any salt which retains the activity of the parent compound and does not impart any deleterious or untoward effect on the subject to which it is administered and in the context in which it is administered.
- the preferred compounds of the invention include, but are not limited to, retinoic acid including tretinoin, 13-cis retinoic acid, 9-cz.s-retinoic acid, acetylenic retinoids including tazarotene and adapalene.
- retinoic acid including tretinoin, 13-cis retinoic acid, 9-cz.s-retinoic acid, acetylenic retinoids including tazarotene and adapalene.
- a "therapeutically-active retinoid” is a compound which, when applied topically, exhibits or possesses a biological action similar to retinoic acid (i.e., similar to vitamin A acid).
- these retinoids include those compounds, synthetic or natural, which have one or more of the therapeutic activities known for retinoic acid. Such activities include but are not limited to binding to and activating RARs, treating and preventing cancer and other proliferative disorders, acting as differentiating agents or
- vinylogs are desmethyl retinoyl groups having 1 or 2 additional vinyl groups relative to retinoic acid.
- such compounds include 2,6,6,-trimethyl-l-(10'-carboxy-deca-r,3',5',7',9'-pentaenyl)cyclohex-l-ene and 2,6,6-trimethyl- 1 -( 12'-carboxy-dodeca- 1 ',3',5',7',9', 11 '-hexaenyl)cyclohex- 1 -ene.
- These groups are also referred to as C20 and C22 vinylogs of desmethyl retinoic acid and are described in U.S. Patent No. 3,882,244.
- the vinylogs of this invention can be prepared from a retinoyl group, any therapeutically active retinoid carboxyl group, or any group of the formula
- acetylenic retinoids of the invention are the compounds of the formula represented by
- X is S, O, or NR' where R' is hydrogen or lower alkyl; R is hydrogen or lower alkyl; A is pyridinyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl; n is 0- 2; and B is H, — COOH or a pharmaceutically acceptable salt, ester or amide thereof, — CH 2 OH or an ether or ester derivative, or — CHO or an acetal derivative, or —COR, or a ketal derivative where R, is — (CH 2 ) m CH 3 where m is 0-4.
- esters refers to and covers any compound falling within the definition of that term as classically used in organic chemistry. Where A is — COOH, this term covers the products derived from treatment of this function with alcohols. Where the ester is derived from compounds where A is — CH 2 OH, this term covers compounds of the formula — CH 2 OOCR where R is any substituted or unsubstituted aliphatic, aromatic or aliphatic-aromatic group.
- esters are derived from the saturated aliphatic alcohols or acids often or fewer carbon atoms or the cyclic or saturated aliphatic cyclic alcohols and acids of 5 to 10 carbon atoms.
- Particularly preferred aliphatic esters are those derived from lower alkyl acids and alcohols.
- lower alkyl means having 1-6 carbon atoms.
- phenyl or lower alkylphenyl esters are also preferred.
- amide has the meaning generally accorded that term in organic chemistry. In this instance it includes the unsubstituted amides and all aliphatic and aromatic mono- and di-substituted amides.
- Preferred amides are the mono- and di-substituted amides derived from the saturated aliphatic radicals often or fewer carbon atoms or the cyclic or saturated aliphatic-cyclic radicals of 5 to 10 carbon atoms. Particularly preferred amides are those derived from lower alkyl amines. Also preferred are mono- and di-substituted amides derived from the phenyl or lower alkylphenyl amines. Unsubstituted amides are also preferred.
- Acetals and ketals includes the radicals of the formula — CK where K is (— OR) 2 .
- R is lower alkyl.
- K may be — OR,O— where R, is lower alkyl of 2-5 carbon atoms, straight chain or branched.
- the preferred acetylenic retinoid compounds of this invention are those where the ethynyl group and the B group are attached to the 2 and 5 positions respectively of a pyridine ring (the 6 and 3 positions in the nicotinic acid nomenclature being equivalent to the 2/5 designation in the pyridine nomenclature) or the 5 and 2 positions respectively of a thiophene group respectively; n is 0; and B is —COOH, an alkali metal salt or organic amine salt, or a lower alkyl ester, or — CH 2 OH and the lower alkyl esters and ethers thereof, or —CHO and acetal derivatives thereof.
- the preferred compounds include: ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)-nicotinate;
- the compounds of the invention can be purchased or made by methods known in the art. One means to make such compounds is provided in U.S. Patent No. 5,089,509 which is hereby inco ⁇ orated herein by reference.
- the "retinoid composition” contains the retinoid compounds of the invention in amounts suitable for topical use on humans. Such compositions may be in the form of a gel, cream, lotion, ointment, cleanser or solution and include a variety of preservatives, carriers and other inactive or active ingredients.
- therapeutically-effective amount refers to that amount of a therapeutically-active retinoid necessary to administer to a human patient to treat psoriasis. Such amounts depend on the retinoid and its bioavailability but can range from about 0.01% to about 10% by weight, or preferably from about 0.025% to about 1-5 % by weight. For tazarotene, commercially available preparations of 0.05% and 0.1% are effective. Therapeutically-effective amounts can be readily determined by one of ordinary skill in the art.
- su ⁇ risingly good results are obtainable using short-contact retinoid therapy. Not only does it appear that there is no loss of effectiveness of the active retinoid ingredient (as compared with conventional extended-contact therapy), but also that the effectiveness may be enhanced in some instances. Even more important, the adverse reactions are substantially reduced to tolerable or even negligible levels, thereby resulting in the ability and willingness of the user to adhere to the novel regimen. This combination of effects, i.e., equal or enhanced effectiveness, reduction in adverse reactions, and regimen adherence, yields su ⁇ risingly improved therapeutic efficacy.
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU28778/00A AU2877800A (en) | 1999-02-12 | 2000-02-10 | Short contact treatment of psoriasis with topical retinoids |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US24938799A | 1999-02-12 | 1999-02-12 | |
US09/249,387 | 1999-02-12 | ||
US09/249,386 | 1999-02-12 | ||
US09/249,386 US6048902A (en) | 1999-02-12 | 1999-02-12 | Short contact treatment of psoriasis with topical retinoids |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000047211A1 true WO2000047211A1 (en) | 2000-08-17 |
Family
ID=26940026
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/003457 WO2000047211A1 (en) | 1999-02-12 | 2000-02-10 | Short contact treatment of psoriasis with topical retinoids |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU2877800A (en) |
WO (1) | WO2000047211A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10251895B2 (en) * | 2015-06-18 | 2019-04-09 | Valeant Pharmaceuticals North America | Topical compositions and methods for treating psoriasis |
US20190133943A1 (en) * | 2015-06-18 | 2019-05-09 | Valeant Pharmaceuticals North America | Topical compositions and methods for treating skin diseases |
US11213587B2 (en) | 2010-11-22 | 2022-01-04 | Bausch Health Ireland Limited | Pharmaceutical formulations containing corticosteroids for topical administration |
US11311482B2 (en) | 2017-05-12 | 2022-04-26 | Bausch Health Us, Llc | Topical compositions and methods for treating skin diseases |
US11839656B2 (en) | 2010-11-22 | 2023-12-12 | Bausch Health Ireland Limited | Pharmaceutical formulations containing corticosteroids for topical administration |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5516793A (en) * | 1993-04-26 | 1996-05-14 | Avon Products, Inc. | Use of ascorbic acid to reduce irritation of topically applied active ingredients |
US5650279A (en) * | 1995-01-27 | 1997-07-22 | Allergan, Inc. | Gene sequence induced in skin by retinoids |
US5719195A (en) * | 1995-05-05 | 1998-02-17 | 4 Thought Technologies | Treatment of psoriasis with 11-cis-retinoic acid |
-
2000
- 2000-02-10 WO PCT/US2000/003457 patent/WO2000047211A1/en active Application Filing
- 2000-02-10 AU AU28778/00A patent/AU2877800A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5516793A (en) * | 1993-04-26 | 1996-05-14 | Avon Products, Inc. | Use of ascorbic acid to reduce irritation of topically applied active ingredients |
US5650279A (en) * | 1995-01-27 | 1997-07-22 | Allergan, Inc. | Gene sequence induced in skin by retinoids |
US5719195A (en) * | 1995-05-05 | 1998-02-17 | 4 Thought Technologies | Treatment of psoriasis with 11-cis-retinoic acid |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11213587B2 (en) | 2010-11-22 | 2022-01-04 | Bausch Health Ireland Limited | Pharmaceutical formulations containing corticosteroids for topical administration |
US11839656B2 (en) | 2010-11-22 | 2023-12-12 | Bausch Health Ireland Limited | Pharmaceutical formulations containing corticosteroids for topical administration |
US11957753B2 (en) | 2010-11-22 | 2024-04-16 | Bausch Health Ireland Limited | Pharmaceutical formulations containing corticosteroids for topical administration |
US10251895B2 (en) * | 2015-06-18 | 2019-04-09 | Valeant Pharmaceuticals North America | Topical compositions and methods for treating psoriasis |
US20190133943A1 (en) * | 2015-06-18 | 2019-05-09 | Valeant Pharmaceuticals North America | Topical compositions and methods for treating skin diseases |
US10426787B2 (en) * | 2015-06-18 | 2019-10-01 | Bausch Health Us, Llc | Topical compositions and methods for treating psoriasis |
US11648256B2 (en) | 2015-06-18 | 2023-05-16 | Bausch Health Ireland Limited | Topical compositions and methods for treating psoriasis |
US11679115B2 (en) | 2015-06-18 | 2023-06-20 | Bausch Health Ireland Limited | Topical compositions and methods for treating psoriasis |
US11679116B2 (en) | 2015-06-18 | 2023-06-20 | Bausch Health Ireland Limited | Topical compositions and methods for treating psoriasis |
US11311482B2 (en) | 2017-05-12 | 2022-04-26 | Bausch Health Us, Llc | Topical compositions and methods for treating skin diseases |
Also Published As
Publication number | Publication date |
---|---|
AU2877800A (en) | 2000-08-29 |
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