WO2000021486A3 - Prevention of uv-induced functional vitamin a deficiency through use of topically applied retinoid - Google Patents
Prevention of uv-induced functional vitamin a deficiency through use of topically applied retinoid Download PDFInfo
- Publication number
- WO2000021486A3 WO2000021486A3 PCT/US1999/023591 US9923591W WO0021486A3 WO 2000021486 A3 WO2000021486 A3 WO 2000021486A3 US 9923591 W US9923591 W US 9923591W WO 0021486 A3 WO0021486 A3 WO 0021486A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- retinoid
- vitamin
- skin
- irradiation
- rxr
- Prior art date
Links
- 150000004492 retinoid derivatives Chemical class 0.000 title abstract 4
- 208000010011 Vitamin A Deficiency Diseases 0.000 title abstract 2
- 230000002265 prevention Effects 0.000 title 1
- 108091008679 retinoid hormone receptors Proteins 0.000 abstract 5
- 102000027483 retinoid hormone receptors Human genes 0.000 abstract 5
- 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 abstract 4
- 229930002330 retinoic acid Natural products 0.000 abstract 4
- 101001093899 Homo sapiens Retinoic acid receptor RXR-alpha Proteins 0.000 abstract 3
- 102100035178 Retinoic acid receptor RXR-alpha Human genes 0.000 abstract 3
- 108090000623 proteins and genes Proteins 0.000 abstract 3
- 229960001727 tretinoin Drugs 0.000 abstract 3
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 abstract 3
- 102100038504 Cellular retinoic acid-binding protein 2 Human genes 0.000 abstract 2
- 108010011716 cellular retinoic acid binding protein II Proteins 0.000 abstract 2
- 238000001727 in vivo Methods 0.000 abstract 2
- 230000006698 induction Effects 0.000 abstract 2
- 108020004999 messenger RNA Proteins 0.000 abstract 2
- 230000001105 regulatory effect Effects 0.000 abstract 2
- GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 abstract 1
- 208000005623 Carcinogenesis Diseases 0.000 abstract 1
- 206010051246 Photodermatosis Diseases 0.000 abstract 1
- 102000012211 Retinoic Acid 4-Hydroxylase Human genes 0.000 abstract 1
- 108010022037 Retinoic Acid 4-Hydroxylase Proteins 0.000 abstract 1
- 230000001668 ameliorated effect Effects 0.000 abstract 1
- 229960005084 calcitriol Drugs 0.000 abstract 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 abstract 1
- 230000036952 cancer formation Effects 0.000 abstract 1
- 231100000504 carcinogenesis Toxicity 0.000 abstract 1
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 230000002939 deleterious effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000006870 function Effects 0.000 abstract 1
- 230000014509 gene expression Effects 0.000 abstract 1
- 230000037311 normal skin Effects 0.000 abstract 1
- 230000008845 photoaging Effects 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 230000019491 signal transduction Effects 0.000 abstract 1
- 230000004215 skin function Effects 0.000 abstract 1
- 229930003231 vitamin Natural products 0.000 abstract 1
- 229940088594 vitamin Drugs 0.000 abstract 1
- 239000011782 vitamin Substances 0.000 abstract 1
- 235000013343 vitamin Nutrition 0.000 abstract 1
- 150000002266 vitamin A derivatives Chemical class 0.000 abstract 1
- 102000009310 vitamin D receptors Human genes 0.000 abstract 1
- 108050000156 vitamin D receptors Proteins 0.000 abstract 1
- 150000003722 vitamin derivatives Chemical class 0.000 abstract 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
- A61K31/185—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
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
-
- 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
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Toxicology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
Abstract
The vitamin A metabolite all-trans retinoic acid (RA) is critical for normal skin function. Ultraviolet irradiation (UV) markedly reduces the mRNA and protein of the two major nuclear retinoid receptors, RAR-η and RXR-α in human skin in vivo. One half the dose of UV that causes skin reddening was sufficient to reduce retinoid receptor mRNA levels. Maximal reduction of RAR-η and RXR-α proteins occurred between 8 and 16 hours after UV irradiation. With multiple exposures to UV, RXR-α remained decreased, but RAR-η recovered to normal levels. Application of RA 24 hours before UV exposure partially prevented loss of nuclear retinoid receptors. UV irradiation completely prevented RA induction of two retinoid receptor-regulated genes, cellular retinoic acid binding protein-II(CRABP-II) and RA 4-hydroxylase. In contrast, UV irradiation did not affect 1,25-dihydroxyvitamin D3 induction of the vitamin D receptor-regulated gene, vitamin 0 24-hydroxylase, indicating that UV selectively interferes with the retinoid-signaling pathway. These data demonstrate for the first time that UV specially reduces retinoid receptor levels and dramatically suppresses retinoid-responsive gene expression in human skin in vivo. In effect, UV causes a functional vitamin A deficiency that could have deleterious effects on skin function, contributing to skin photoaging and carcinogenesis, which can be ameliorated by application of a retinoid prior to exposure.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL14234999A IL142349A0 (en) | 1998-10-14 | 1999-10-12 | A topical composition containing a retinoid |
| AU65133/99A AU6513399A (en) | 1998-10-14 | 1999-10-12 | Prevention of uv-induced functional vitamin a deficiency through use of topically applied retinoid |
| JP2000575462A JP2003524604A (en) | 1998-10-14 | 1999-10-12 | Method of preventing UV-induced functional vitamin A deficiency by topical application of retinoids |
| BR9914531-6A BR9914531A (en) | 1998-10-14 | 1999-10-12 | Prevention of IV-induced functional vitamin A deficiency through the use of topically applied retinoid |
| CA002344696A CA2344696A1 (en) | 1998-10-14 | 1999-10-12 | Prevention of uv-induced functional vitamin a deficiency through use of topically applied retinoid |
| NO20011449A NO20011449L (en) | 1998-10-14 | 2001-03-22 | Method of Inhibiting UV-Induced Vitamin A Deficiency Using Topically Used Retinoid |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10424598P | 1998-10-14 | 1998-10-14 | |
| US60/104,245 | 1998-10-14 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2000021486A2 WO2000021486A2 (en) | 2000-04-20 |
| WO2000021486A9 WO2000021486A9 (en) | 2000-11-23 |
| WO2000021486A3 true WO2000021486A3 (en) | 2007-08-23 |
Family
ID=22299409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1999/023591 WO2000021486A2 (en) | 1998-10-14 | 1999-10-12 | Prevention of uv-induced functional vitamin a deficiency through use of topically applied retinoid |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JP2003524604A (en) |
| AU (1) | AU6513399A (en) |
| BR (1) | BR9914531A (en) |
| CA (1) | CA2344696A1 (en) |
| IL (1) | IL142349A0 (en) |
| WO (1) | WO2000021486A2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807900A (en) * | 1995-03-31 | 1998-09-15 | Hoffmann-La Roche, Inc. | Method for identifying compounds having increased activity for the repair of skin photodamage |
-
1999
- 1999-10-12 AU AU65133/99A patent/AU6513399A/en not_active Abandoned
- 1999-10-12 WO PCT/US1999/023591 patent/WO2000021486A2/en active Application Filing
- 1999-10-12 BR BR9914531-6A patent/BR9914531A/en not_active Application Discontinuation
- 1999-10-12 IL IL14234999A patent/IL142349A0/en unknown
- 1999-10-12 JP JP2000575462A patent/JP2003524604A/en not_active Withdrawn
- 1999-10-12 CA CA002344696A patent/CA2344696A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807900A (en) * | 1995-03-31 | 1998-09-15 | Hoffmann-La Roche, Inc. | Method for identifying compounds having increased activity for the repair of skin photodamage |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2344696A1 (en) | 2000-04-20 |
| WO2000021486A2 (en) | 2000-04-20 |
| JP2003524604A (en) | 2003-08-19 |
| WO2000021486A9 (en) | 2000-11-23 |
| IL142349A0 (en) | 2002-03-10 |
| AU6513399A (en) | 2000-05-01 |
| BR9914531A (en) | 2001-07-03 |
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