WO1992009276A1 - Aromatic aldehydes and derivatives and pharmaceutical compositions thereof useful for the treatment of skin diseases and arthritis - Google Patents
Aromatic aldehydes and derivatives and pharmaceutical compositions thereof useful for the treatment of skin diseases and arthritis Download PDFInfo
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- WO1992009276A1 WO1992009276A1 PCT/NO1991/000147 NO9100147W WO9209276A1 WO 1992009276 A1 WO1992009276 A1 WO 1992009276A1 NO 9100147 W NO9100147 W NO 9100147W WO 9209276 A1 WO9209276 A1 WO 9209276A1
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- 238000011282 treatment Methods 0.000 title claims abstract description 35
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 206010003246 arthritis Diseases 0.000 title description 4
- 229940053991 aldehydes and derivative Drugs 0.000 title description 3
- 150000003934 aromatic aldehydes Chemical class 0.000 title description 3
- 208000017520 skin disease Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- 201000010099 disease Diseases 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 230000004663 cell proliferation Effects 0.000 claims abstract description 9
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- -1 cyclic acetal Chemical class 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 8
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 claims description 4
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 4
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 150000003555 thioacetals Chemical class 0.000 claims description 4
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
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- KZSNJWFQEVHDMF-FXLFCPKBSA-N (2S)-2-amino-3-methyl(214C)butanoic acid Chemical compound N[14C@@H](C(C)C)C(=O)O KZSNJWFQEVHDMF-FXLFCPKBSA-N 0.000 description 1
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- 208000023275 Autoimmune disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 206010061809 Cervix carcinoma stage 0 Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010036941 Cyclosporins Proteins 0.000 description 1
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- 239000001828 Gelatine Substances 0.000 description 1
- JYGXADMDTFJGBT-VWUMJDOOSA-N Hydrocortisone Natural products O=C1CC[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 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
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- 150000003935 benzaldehydes Chemical class 0.000 description 1
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 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
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- 229930182912 cyclosporin Natural products 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
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- 229910052740 iodine Inorganic materials 0.000 description 1
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- 231100000518 lethal Toxicity 0.000 description 1
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- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
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- 159000000000 sodium salts Chemical class 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 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 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- 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
- A61K31/11—Aldehydes
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Definitions
- compositions thereof useful for the treatment of skin are compositions thereof useful for the treatment of skin
- Present invention concern aromatic aldehydes and derivatives thereof, which are useful for the treatment of diseases which arise due to an elevated cellular proliferation (i.e. the rapid and repeated reproduction by cell division), such as psoriasis, inflammatory diseases, rheumatic diseases and allergic dermatologic reactions.
- Psoriasis for example, is a dermatologic disease which is characterized by rapid turnover of the epidermis.
- patients suffering from psoriasis may also suffer from autoimmune and rheumatic diseases, such as for instance lupus and arthritis.
- psoriasis is treated with hydrocortison derivatives, ditranole, tar salve or, in serious cases, with immuno-depressants such as cytostatica, cyclosporins or the like. All these treatments give rise to unwanted secondary effects.
- the compounds according to present invention are aromatic benzaldehydes or derivatives thereof of the following formula (I):
- Y is H or D
- X 1 and X 2 may be the same or different and may be OR
- R, R 1 and R 2 may be H or an alkyl of 1-5
- Ar is phenyl which may be unsubstituted or substituted in one or several positions by one or more of the following substituents which may be alkyl with 1-5 C-atoms, cycloalkyl of 3-6 C-atoms, halogen, nitro, amino, monoalkylamino or dialkylamino, wherein the alkylgroups have 1-5 C- atoms, OR wherein R may be H or an alkylgroup of 1-5C-atoms; or pharmaceutically acceptable salts thereof.
- alkyl groups herein may be straight-chained or branched, and especially preferred are methyl, ethyl, propyl and t- butyl.
- the halogens may be any of chlorine, bromine, fluorine and iodine.
- the pharmaceutically acceptable salts may be alkali metal salts, such as sodium salts, earth alkali metal salts, such as magnesium or calsium salts, ammoniumsalts, salts with organic aminobases or the like.
- Some of the compounds according to present invention are known as anticancer agents among other from EP215395,
- J63264411, J88009490, J55069510 and EP283139 J63264411, J88009490, J55069510 and EP283139.
- the compounds of formula I may be used for the treatment of diseases such as psoriasis, inflammatory diseases, rheumatic diseases and allergic dermatologic reactions.
- Dermatologic abnormalities such as psoriasis are often characterized by rapid turnover of the epidermis. While normal skin produces ca. 1250 new cells/day/cm 2 of skin consisting of about 27,000 cells, psoriatic skin produces 35,000 new cells/day/cm 2 from 52,000 cells. The cells involved in these diseases are however "normal" cells reproducing rapidly and repeatedly by cell division. While the cell cycle of normal skin cells is approximately 311 hours, this progression through the division cycle is reduced to about 10 to 36 hours for psoriatic skin.
- diseases which may be treated by the compounds of formula I are rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE), acne, Bechterew's arthritis, systemic seleroderma and seborrhea.
- Human cells of the established line NHIK 3025 originating from a cervical carcinoma in situ (Nordbye, K. and Oftebro, R., Exp. Cell Res., 58: 458, 1969), Oftebro, R. and Nordbye, K., Exp. Cell Res., 58: 459-460, 1969) were cultivated in medium E2a (Puck et al., J. Exp. Med., 106: 145-165, 1957) supplemented with 20% human (prepared at the laboratory) and 10% horse serum (Grand Island Biological Co.).
- the cells are routinely grown as monolayers in tissue culture flasks. The cells do not move around after they have attached, a quality which enables us to observe the same cells in an inverted microscope for several cell generations.
- the cells were kept in continuous exponential growth by frequent reculturing, i.e. every second and third day, and were obtained by repeated selection of mitotic cells
- the NHIK 3025 cells have a medium cell-cycle time of ⁇ 18 hr, with median G 1 , S 1 and G 2 durations of ⁇ 7, ⁇ 8 and ⁇ 2.5 hr, respectively.
- Zilascorb ( 2 H) was given in the G1- to early S-phases of the cell cycle. Thereafter the time of cell division was recorded.
- the data of table 3 should be evaluated on basis of those of table 1 shoving that 1 mM Zilascorb ( 2 H) reduces protein synthesis to 1.73 %/h from 3.68 %/h which was the protein synthesis in the control. Since NHIK 3025 cells usually have a protein degradation just above 1 %/h, net protein accumulation is not more than 0.7 %/h in the treated cells during treatment. Thus, during treatment the protein doubl ing time is
- the compounds may according to the present invention be administrered in any pharmaceutical formulation suitable for topical or systemic therapy.
- the pharmaceutical preparations may be administrered enterally, parenterally or topically.
- the compounds of formula I may be formulated e.g. as soft or hard gelatine capsules, tablets, granules, grains or powders, dragees, syrups, suspensions, solutions or suppositories.
- the compounds of formula I When administrered topically the compounds of formula I may be formulated as a lotion, salve, ointment, cream, gel, tincture, spray, lotion or the like containing the compounds of formula I in admixture with non-toxic, inert, solid or liquid carriers which are usual in topical preparations. It is especially suitable to use a formulation which protects the active ingredient against air, water and the like.
- the preparations can contain inert or pharmacodynamically active additives. Tablets or granulates e.g. can contain a series of binding agents, filler materials, carrier substances or diluents. Liquid preparations may be present, for example, in the form of a sterile solution. Capsules can contain a filler material or thickening agent in addition to the active ingredient. Furthermore, flavour-improving additives as well as the substances usually used as preserving, stabilizing, moisture-retaining and emulsifying agents, salts for varying the osmotic pressure, buffers and other additives may also be present.
- the dosages in which the preparations are administered can vary according to the mode of use and the route of use, as well as to the requirements of the patient.
- a daily dosage for a systemic therapy for an adult average patient of 70 kg body weight will be about 0.1-50 mg/kg/day preferably 1-15 mg/kg/day.
- the suitable salve or ointment can contain from 0.1-20% by weight of the active ingredient, especially 1-5%.
- the proportion of active ingredient in the pharmaceutical composition will vary depending upon the type of preparation, but may generally be within the range of approximately 0.1 to 20% by weight for oral administration and for absorption through mucous membranes, and about 0.01 to 10% by weight for parenteral administration.
- the pharmaceutical preparation of the compound of formula I can contain an antioxidant, e.r. tocopherol, N-methyl-tocopheramine, butylated hydroxyanisole, ascorbic acid or butylated hydroxytoluene.
- an antioxidant e.r. tocopherol, N-methyl-tocopheramine, butylated hydroxyanisole, ascorbic acid or butylated hydroxytoluene.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Molecular Biology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4500554A JPH06503084A (en) | 1990-11-30 | 1991-11-25 | Aromatic aldehydes and their derivatives and their pharmaceutical compositions useful in the treatment of skin diseases and arthritis |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB909026080A GB9026080D0 (en) | 1990-11-30 | 1990-11-30 | Pharmaceutical compositions |
GB9026080.3 | 1990-11-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992009276A1 true WO1992009276A1 (en) | 1992-06-11 |
Family
ID=10686268
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/NO1991/000147 WO1992009276A1 (en) | 1990-11-30 | 1991-11-25 | Aromatic aldehydes and derivatives and pharmaceutical compositions thereof useful for the treatment of skin diseases and arthritis |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0559728A1 (en) |
JP (1) | JPH06503084A (en) |
AU (1) | AU9035691A (en) |
CA (1) | CA2095334A1 (en) |
GB (1) | GB9026080D0 (en) |
WO (1) | WO1992009276A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001002412A1 (en) * | 1999-07-05 | 2001-01-11 | Norsk Hydro Asa | 5-nitrofurfural derivatives |
WO2003043621A1 (en) * | 2001-11-16 | 2003-05-30 | Cutanix Corporation | Pharmaceutical and cosmetic compositions containing oxy group-bearing aromatic aldehydes |
EP1622554A1 (en) * | 2003-05-15 | 2006-02-08 | Cutanix Corporation | Compositions containing a combination of a pharmaceutical agent or a cosmetic agent and an oxy group-bearing aromatic aldehyde |
US8236288B2 (en) | 2011-01-07 | 2012-08-07 | Skinmedica, Inc. | Melanin modification compositions and methods of use |
US8246969B2 (en) | 2001-11-16 | 2012-08-21 | Skinmedica, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4778785A (en) * | 1985-09-06 | 1988-10-18 | Kaken Pharmaceutical Co., Ltd. | Pharmaceutical composition for retarding and reducing cachexia |
US4874780A (en) * | 1987-03-11 | 1989-10-17 | Norsk Hydro A.S. | Anticancer compounds |
-
1990
- 1990-11-30 GB GB909026080A patent/GB9026080D0/en active Pending
-
1991
- 1991-11-25 JP JP4500554A patent/JPH06503084A/en active Pending
- 1991-11-25 WO PCT/NO1991/000147 patent/WO1992009276A1/en not_active Application Discontinuation
- 1991-11-25 EP EP92900278A patent/EP0559728A1/en not_active Withdrawn
- 1991-11-25 CA CA002095334A patent/CA2095334A1/en not_active Abandoned
- 1991-11-25 AU AU90356/91A patent/AU9035691A/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4778785A (en) * | 1985-09-06 | 1988-10-18 | Kaken Pharmaceutical Co., Ltd. | Pharmaceutical composition for retarding and reducing cachexia |
US4874780A (en) * | 1987-03-11 | 1989-10-17 | Norsk Hydro A.S. | Anticancer compounds |
Non-Patent Citations (2)
Title |
---|
Dialog Information Services, File WPI, Dialog Accession No. 002530578, WPI Accession No. 80-486050/28, Mitsubishi Chem Ind Ltd: "Carcinostatic agent". * |
Dialog Information Services, File WPI, Dialog Accession No. 004412470, WPI Accession No. 85-239348/39, Rikagaku Kenkysho: "Carcinostatic agent". * |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001002412A1 (en) * | 1999-07-05 | 2001-01-11 | Norsk Hydro Asa | 5-nitrofurfural derivatives |
US8246969B2 (en) | 2001-11-16 | 2012-08-21 | Skinmedica, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
US9107874B2 (en) | 2001-11-16 | 2015-08-18 | Allergan, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
EA009281B1 (en) * | 2001-11-16 | 2007-12-28 | Катаникс Корпорейшн | Pharmaceutical and cosmetic compositions containing oxy group-bearing aromatic aldehydes |
WO2003043621A1 (en) * | 2001-11-16 | 2003-05-30 | Cutanix Corporation | Pharmaceutical and cosmetic compositions containing oxy group-bearing aromatic aldehydes |
US8246971B2 (en) | 2001-11-16 | 2012-08-21 | Skinmedica, Inc. | Compositions containing aromatic aldehydes and their use in treatment |
US8268336B2 (en) | 2001-11-16 | 2012-09-18 | Skinmedica, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
US8496951B2 (en) | 2001-11-16 | 2013-07-30 | Allergan, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
US10702515B2 (en) | 2001-11-16 | 2020-07-07 | Allergan, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
US9895361B2 (en) | 2001-11-16 | 2018-02-20 | Allergan, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
EP1622554A4 (en) * | 2003-05-15 | 2008-01-02 | Bioform Medical Inc | Compositions containing a combination of a pharmaceutical agent or a cosmetic agent and an oxy group-bearing aromatic aldehyde |
EP1622554A1 (en) * | 2003-05-15 | 2006-02-08 | Cutanix Corporation | Compositions containing a combination of a pharmaceutical agent or a cosmetic agent and an oxy group-bearing aromatic aldehyde |
US8236288B2 (en) | 2011-01-07 | 2012-08-07 | Skinmedica, Inc. | Melanin modification compositions and methods of use |
US9044404B2 (en) | 2011-01-07 | 2015-06-02 | Allergan, Inc. | Melanin modification compositions and methods of use |
US8778315B2 (en) | 2011-01-07 | 2014-07-15 | Allergan, Inc. | Melanin modification compositions and methods of use |
Also Published As
Publication number | Publication date |
---|---|
AU9035691A (en) | 1992-06-25 |
EP0559728A1 (en) | 1993-09-15 |
GB9026080D0 (en) | 1991-01-16 |
JPH06503084A (en) | 1994-04-07 |
CA2095334A1 (en) | 1992-05-31 |
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