WO2002048136A1 - Inhibiteurs de la proliferation des keratinocytes - Google Patents
Inhibiteurs de la proliferation des keratinocytes Download PDFInfo
- Publication number
- WO2002048136A1 WO2002048136A1 PCT/JP2001/010928 JP0110928W WO0248136A1 WO 2002048136 A1 WO2002048136 A1 WO 2002048136A1 JP 0110928 W JP0110928 W JP 0110928W WO 0248136 A1 WO0248136 A1 WO 0248136A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- zearalenones
- keratinocytes
- proliferation
- skin disease
- keratinocyte
- Prior art date
Links
- 210000002510 keratinocyte Anatomy 0.000 title claims abstract description 63
- 230000035755 proliferation Effects 0.000 title claims abstract description 43
- 239000003112 inhibitor Substances 0.000 title claims abstract description 14
- 208000017520 skin disease Diseases 0.000 claims abstract description 29
- 230000002159 abnormal effect Effects 0.000 claims abstract description 19
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
- 230000003449 preventive effect Effects 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 25
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 230000001225 therapeutic effect Effects 0.000 claims description 10
- 230000012010 growth Effects 0.000 claims description 8
- 230000000069 prophylactic effect Effects 0.000 claims description 8
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 206010052428 Wound Diseases 0.000 claims description 4
- 208000027418 Wounds and injury Diseases 0.000 claims description 4
- 230000000172 allergic effect Effects 0.000 claims description 4
- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 208000012868 Overgrowth Diseases 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 239000003966 growth inhibitor Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 239000002609 medium Substances 0.000 description 11
- MBMQEIFVQACCCH-UHFFFAOYSA-N trans-Zearalenon Natural products O=C1OC(C)CCCC(=O)CCCC=CC2=CC(O)=CC(O)=C21 MBMQEIFVQACCCH-UHFFFAOYSA-N 0.000 description 8
- MBMQEIFVQACCCH-QBODLPLBSA-N zearalenone Chemical compound O=C1O[C@@H](C)CCCC(=O)CCC\C=C\C2=CC(O)=CC(O)=C21 MBMQEIFVQACCCH-QBODLPLBSA-N 0.000 description 8
- 230000004663 cell proliferation Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000012258 culturing Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002689 soil Substances 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 210000004920 epithelial cell of skin Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000009422 growth inhibiting effect Effects 0.000 description 2
- -1 leukin 1 Chemical compound 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- VSIVTUIKYVGDCX-UHFFFAOYSA-M sodium;4-[2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].COC1=CC([N+]([O-])=O)=CC=C1[N+]1=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=NN1C1=CC=C([N+]([O-])=O)C=C1 VSIVTUIKYVGDCX-UHFFFAOYSA-M 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 241000287463 Phalacrocorax Species 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 206010040867 Skin hypertrophy Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only 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
- A61K31/33—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
- 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P37/02—Immunomodulators
-
- 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
- the present invention provides a keratinocyte proliferation inhibitor containing zearalenone as an active ingredient, a therapeutic or prophylactic agent for a skin disease associated with abnormal proliferation of keratinocytes, containing zearalenone as an active ingredient, and administering an effective amount of zearalenone.
- a method of treating and preventing a skin disease associated with abnormal proliferation of keratinocytes which comprises administering an effective amount of zelarenones, the use of zelarenones for producing a keratinocyte proliferation inhibitor, and the use of keratinocytes.
- zearalenones for the manufacture of a therapeutic or prophylactic agent for a skin disease associated with abnormal growth, an effective amount of zearalenones, a kit for inhibiting the growth of keratinocytes including instructions for use, and an effective amount of zearalenones Abnormal growth of keratinocytes, including Cormorants relates to a kit for the treatment or prevention of skin disorders.
- keratinocytes which are skin epithelial cells
- keratinocytes which are skin epithelial cells
- the keratinocyte cell proliferation control mechanism has been disrupted, and skin thickening due to pathological abnormal proliferation of skin epithelial cells has been observed.
- cytokins such as epidermal growth factor and other growth factors such as leukin 1, 4, 6, and 8
- leukin 1, 4, 6, and 8 Although recognized (Gen. Pharmac., (1998) 5, 619-622), the detailed mechanism of keratinocyte proliferation in the above-mentioned diseases is unknown.
- a substance that suppresses the pathological cell proliferation of keratinocytes it can be expected to be used as a therapeutic agent for various skin diseases characterized by abnormal proliferation of keratinocytes. Furthermore, any substance that does not affect the proliferation of stromal cells such as fibroblasts is expected to be useful in reducing side effects.
- An object of the present invention is to provide a keratinocyte proliferation inhibitor. Another object of the present invention is to provide an agent for treating or preventing a skin disease associated with keratinocyte proliferation.
- the present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that certain zearalenones have a keratinocyte-specific cell growth inhibitory action, and completed the present invention based on this finding. .
- the present invention provides a keratinocyte proliferation inhibitor comprising a zearalenone as an active ingredient. Further, the present invention provides a therapeutic or preventive agent for a skin disease associated with abnormal proliferation of keratinocytes, comprising a zearalenone as an active ingredient.
- the present invention provides a method for inhibiting keratinocyte proliferation, which comprises administering an effective amount of a zearalenone to a patient in need thereof. Further, the present invention provides a method for treating and preventing a skin disease associated with abnormal proliferation of keratinocytes, which comprises administering an effective amount of zearalenones to a patient in need thereof.
- the present invention relates to zearalenone for producing a keratinocyte proliferation inhibitor. Provides a kind of use.
- the present invention also provides use of zearalenones for producing a therapeutic or prophylactic agent for a skin disease associated with keratinocyte overgrowth.
- the present invention provides a kit for inhibiting the growth of keratinocytes, comprising an effective amount of zearalenones and instructions for use.
- the present invention also provides a kit for treating or preventing a skin disease associated with keratinocyte overgrowth, comprising an effective amount of zearalenones and instructions for use.
- FIG. 1 is a graph showing the inhibitory effect of compound (1) on human keratinocyte proliferation.
- FIG. 2 is a graph showing the inhibitory effect of compound (1) on human keratinocyte proliferation.
- FIG. 3 is a graph showing the effect of compound (1) on human keratinocyte. It is a graph which shows cytotoxicity.
- FIG. 4 is a graph showing the effect of compound (1) on cell proliferation of human fibroblasts.
- zearalenones include zearalenone and its derivatives, for example, as shown below:
- compounds (1) to (3) are preferable, and compound (1) is particularly preferable.
- Skin diseases associated with abnormal proliferation of keratinocytes include the failure of the cell proliferation control mechanism of keratinocytes and the pathological abnormal proliferation of skin epithelial cells. Includes various diseases with thickening. Non-limiting examples of such skin diseases include psoriasis, immune skin diseases, allergic skin diseases, inflammatory skin diseases, chronic wounds, and the like. Keratinocyte proliferation inhibitors are expected to be effective as therapeutic or prophylactic agents.
- the administration form of the medicament containing the keratinocyte proliferation inhibitor of the present invention is not particularly limited, and may be oral administration, parenteral administration, systemic administration, or local administration.
- the medicament of the present invention can be generally administered parenterally, can be administered transdermally as a spray, talmes, lotions, ointments, etc., or intravenously or intramuscularly as an injection Or it can be administered subcutaneously.
- the dose can be appropriately selected depending on the patient's body type, age, physical condition, type and degree of the disease, elapsed time after onset, and the like.In the case of parenteral administration, the dose is generally from 0.01 to 0.1 gg. A dose of O mgZ body weight kg / day, and in the case of oral administration, a dose of 1 ng to 10 g / body weight kgZ day can generally be expected to be effective.
- zearalenones may be used alone or in combination of two or more.
- the keratinocyte proliferation inhibitor and the therapeutic or prophylactic agent for a skin disease associated with keratinocyte abnormal growth of the present invention comprise one or more pharmaceutically acceptable diluents, wetting agents, emulsifiers, dispersants, and auxiliary agents.
- the composition can be administered as a pharmaceutical composition appropriately containing an agent, a preservative, a buffer, a binder, a stabilizer and the like in an appropriate form depending on the intended administration route.
- kit of the present invention includes a pharmaceutical composition comprising zearalenones, a diluent, and any one or more carriers including the various carriers exemplified above, and instructions for use.
- Example 1 Effect of the compound of the present invention on cell proliferation of normal human keratinocytes
- Normal human keratinocytes manufactured by Sanko Junyaku Co., Ltd.
- compound (1) is finalized.
- WST-8 manufactured by Nacalai Tesque
- the reaction was stopped by adding 1/10 volume. Immediately thereafter, the absorbance at 450 nm (reference wavelength: 655 nm) was measured using a microplate reader. A background obtained by performing the same treatment on a medium containing no cells was used as a background, and a value obtained by subtracting the background from the measured value was calculated.
- Compound (1) is 10- 7 ⁇ : L0- 5 mol / L concentration significantly inhibited the growth of Hitokerachinosai Bok of (multiple comparisons Dunnett, ⁇ 0.00l), the IC 5. The value was 4.8 ⁇ 10 ⁇ 8 mol / L.
- compound (1) is 10 ⁇ 7 ⁇ : L0- 5 mol / at a concentration of L significantly inhibited [3 H] thymidine uptake of human keratinocytes (multiple comparisons Dumiett, p rather 0.001), its IC50 The value was 3.2 ⁇ 10 ′ 8 mol / L.
- compound (2) and compound (3) are 10 ⁇ 7 ⁇ : L0- 5 mol / at a concentration of L significantly inhibited [3 H] thymidine uptake of human keratinocytes (multiple comparisons Dumiett, p rather 0.001), its IC50 The value was 3.2 ⁇ 10 ′ 8 mol / L.
- compound (2) and compound (2) is 10 ⁇ 7 ⁇ : L0- 5 mol / at a concentration of L significantly inhibited [3 H] thymidine uptake of human keratinocytes (multiple comparisons Dumiett, p rather 0.001), its IC50 The value was 3.2 ⁇ 10
- Example 2 Examination of cytotoxicity of the compound of the present invention in normal human keratinocytes The cytotoxicity of compound (1) was evaluated by measuring the amount of LDH leaked out of cells. That is, seeded with KGM-2 medium normal human keratinocytes in a 96-well plate at 2X 10 3 per 1 Ueru, final concentration 10, 9-10, 5 Compound (1) after the cells have adhered mol / L. After culturing for 3 days, LDH activity leaked into the medium was measured by LDH-cytotoxicity test ⁇ KO (manufactured by Wako Pure Chemical Industries, Ltd.) using 50 L of 200 L of the culture supernatant. As a positive control, the final concentration of the control was 0.1 ° /. Tween 20 was added to the mixture, and the mixture was treated at 37 ° C. for 15 minutes. The LDH activity of the medium without cells alone was used as the background, and the value obtained by subtracting the background from the measured value was calculated.
- LDH activity of the medium without cells alone
- Compound (1) showed cytotoxicity to human keratinocytes at concentrations of 10- 5 mol / L (multiple comparisons Dunnett, p ⁇ 0.001), was almost completely inhibited keratinocyte proliferation concentrations ( At 10 ⁇ 7 to 10 ⁇ 6 mol / L), no cytotoxicity was observed.
- Example 3 Investigation of the effect of the compound of the present invention on the cell proliferation of normal human fibroblasts A 96-well microplate was prepared so that the number of human fibroblast cell lines WI-38 cells (ATCC) was 2 x 10 3 cells / well. (Falcon) using DMEM medium containing 10% fetal bovine serum. After overnight incubation to allow the cells to be attached thereto were added the compound (1) in such a way that 10- 9 ⁇ 10 6 mol / L , or DMSO as a control such that the final concentration of 1%. After culturing for 3 days, a viable cell counting reagent SF (WST-8, manufactured by Nacalai Tesque) was added to 1/10 of the medium.
- WI-38 cells ATCC
- DMEM medium containing 10% fetal bovine serum
- Fig. 4 shows the results.
- keratinocytes since it has an activity of specifically suppressing the cell proliferation action of keratinocytes, various diseases characterized by abnormal proliferation of keratinocytes (for example, psoriasis, inflammatory, allergic skin diseases, chronic wounds, etc.) ) Is expected to be useful as a therapeutic or prophylactic agent. Further, since it does not substantially affect the proliferation of stromal cells such as fibroblasts, it is expected to be useful as an agent for treating or preventing the above-mentioned diseases with few side effects.
- diseases characterized by abnormal proliferation of keratinocytes for example, psoriasis, inflammatory, allergic skin diseases, chronic wounds, etc.
- stromal cells such as fibroblasts
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
Abstract
La présente invention concerne des inhibiteurs de la prolifération des kératinocytes qui renferment, en tant qu'ingrédient actif, une ou plusieurs zéaralénones; des remèdes ou des prophylactiques pour les maladies cutanées associées à une prolifération anormale des kératinocytes; une méthode permettant d'inhiber la prolifération des kératinocytes qui consiste à utiliser une ou plusieurs zéaralénones selon une posologie efficace; une méthode de traitement ou de prévention des maladies cutanées associées à la prolifération anormale des kératinocytes qui consiste à administrer une ou plusieurs zéaralénones selon une posologie efficace aux patients nécessitant un tel traitement; des trousses permettant d'inhiber la prolifération des kératinocytes qui renferment une ou plusieurs zéaralénones selon une posologie efficace et une notice; des trousses utiles pour traiter ou pour prévenir les maladies cutanées associées à la prolifération anormale des kératinocytes; et l'utilisation d'une ou plusieurs zéaralénones pour produire des inhibiteurs de la prolifération des kératinocytes ou bien des remèdes ou encore des prophylactiques destinés aux maladies cutanées associées à la prolifération anormale des kératinocytes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2002222628A AU2002222628A1 (en) | 2000-12-14 | 2001-12-13 | Keratinocyte proliferation inhibitors |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000-379994 | 2000-12-14 | ||
| JP2000379994A JP2004292314A (ja) | 2000-12-14 | 2000-12-14 | ケラチノサイト増殖抑制剤 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2002048136A1 true WO2002048136A1 (fr) | 2002-06-20 |
Family
ID=18848259
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2001/010928 WO2002048136A1 (fr) | 2000-12-14 | 2001-12-13 | Inhibiteurs de la proliferation des keratinocytes |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP2004292314A (fr) |
| AU (1) | AU2002222628A1 (fr) |
| WO (1) | WO2002048136A1 (fr) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003076424A1 (fr) * | 2002-03-08 | 2003-09-18 | Eisai Co. Ltd. | Composes macrocycliques utiles comme produits pharmaceutiques |
| EP1450784A4 (fr) * | 2001-11-09 | 2005-02-09 | Conforma Therapeutics Corp | Composes de zearalanol inhibant hsp90 et leurs procedes de production et d'utilisation |
| US7601852B2 (en) | 2006-05-11 | 2009-10-13 | Kosan Biosciences Incorporated | Macrocyclic kinase inhibitors |
| US7915306B2 (en) | 2002-03-08 | 2011-03-29 | Eisai Co., Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| US8507696B2 (en) | 2007-12-07 | 2013-08-13 | Eisai R&D Management Co., Ltd. | Intermediates in the synthesis zearalenone macrolide analogs |
| US8609640B2 (en) | 2007-07-25 | 2013-12-17 | Eisai, Inc. | Multikinase inhibitors for use in the treatment of cancer |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008150291A (ja) * | 2005-03-22 | 2008-07-03 | Kyowa Hakko Kogyo Co Ltd | 乾癬治療剤 |
| PL2915804T3 (pl) | 2012-10-31 | 2019-09-30 | Fujifilm Toyama Chemical Co., Ltd. | Nowe pochodne aminy lub ich sole jako inhibitory tnf alfa |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0606044A1 (fr) * | 1992-12-04 | 1994-07-13 | Sandoz Ltd. | Composés de lactones utiles comme agents pharmaceutiques |
| EP0646576A1 (fr) * | 1993-10-01 | 1995-04-05 | F. Hoffmann-La Roche Ag | Analogues de la vitamine D3 |
| JPH0840893A (ja) * | 1993-08-31 | 1996-02-13 | Takeda Chem Ind Ltd | インターロイキン−１産生抑制剤 |
| WO1996013259A2 (fr) * | 1994-10-28 | 1996-05-09 | Cor Therapeutics, Inc. | Procede et combinaisons servant a inhiber les proteine kinases |
| WO1998004264A1 (fr) * | 1996-07-30 | 1998-02-05 | Geomed Inc | Procedes et compositions permettant d'inhiber la proliferation de keratinocytes |
-
2000
- 2000-12-14 JP JP2000379994A patent/JP2004292314A/ja active Pending
-
2001
- 2001-12-13 AU AU2002222628A patent/AU2002222628A1/en not_active Abandoned
- 2001-12-13 WO PCT/JP2001/010928 patent/WO2002048136A1/fr active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0606044A1 (fr) * | 1992-12-04 | 1994-07-13 | Sandoz Ltd. | Composés de lactones utiles comme agents pharmaceutiques |
| JPH0840893A (ja) * | 1993-08-31 | 1996-02-13 | Takeda Chem Ind Ltd | インターロイキン−１産生抑制剤 |
| EP0646576A1 (fr) * | 1993-10-01 | 1995-04-05 | F. Hoffmann-La Roche Ag | Analogues de la vitamine D3 |
| WO1996013259A2 (fr) * | 1994-10-28 | 1996-05-09 | Cor Therapeutics, Inc. | Procede et combinaisons servant a inhiber les proteine kinases |
| WO1998004264A1 (fr) * | 1996-07-30 | 1998-02-05 | Geomed Inc | Procedes et compositions permettant d'inhiber la proliferation de keratinocytes |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1450784A4 (fr) * | 2001-11-09 | 2005-02-09 | Conforma Therapeutics Corp | Composes de zearalanol inhibant hsp90 et leurs procedes de production et d'utilisation |
| US7553979B2 (en) | 2001-11-09 | 2009-06-30 | Conforma Therapeutics Corporation | HSP90-inhibiting zearalanol compounds and methods of producing and using same |
| US8329742B2 (en) | 2002-03-08 | 2012-12-11 | Eisai Co., Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| WO2003076424A1 (fr) * | 2002-03-08 | 2003-09-18 | Eisai Co. Ltd. | Composes macrocycliques utiles comme produits pharmaceutiques |
| AU2003224672B2 (en) * | 2002-03-08 | 2010-02-04 | Eisai R&D Management Co., Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| US7799827B2 (en) | 2002-03-08 | 2010-09-21 | Eisai Co., Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| US7915306B2 (en) | 2002-03-08 | 2011-03-29 | Eisai Co., Ltd. | Macrocyclic compounds useful as pharmaceuticals |
| EP2308861A1 (fr) * | 2002-03-08 | 2011-04-13 | Eisai R&D Management Co., Ltd. | Composés macrocycliques utiles en tant qu'agents pharmaceutiques |
| US7601852B2 (en) | 2006-05-11 | 2009-10-13 | Kosan Biosciences Incorporated | Macrocyclic kinase inhibitors |
| US8609640B2 (en) | 2007-07-25 | 2013-12-17 | Eisai, Inc. | Multikinase inhibitors for use in the treatment of cancer |
| US8937056B2 (en) | 2007-07-25 | 2015-01-20 | Eisai R&D Management Co., Ltd. | Multikinase inhibitors for use in the treatment of cancer |
| US11160783B2 (en) | 2007-07-25 | 2021-11-02 | Eisai R&D Management Co., Ltd. | Multikinase inhibitors for use in the treatment of cancer |
| US8507696B2 (en) | 2007-12-07 | 2013-08-13 | Eisai R&D Management Co., Ltd. | Intermediates in the synthesis zearalenone macrolide analogs |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002222628A1 (en) | 2002-06-24 |
| JP2004292314A (ja) | 2004-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10960012B2 (en) | Bismuth-thiols as antiseptics for biomedical uses, including treatment of bacterial biofilms and other uses | |
| Peng et al. | Dexmedetomidine attenuates lipopolysaccharide-induced proinflammatory response in primary microglia | |
| US11813266B2 (en) | Combination of active agents for the treatment of progressive fibrosing interstitial lung diseases (PF-ILD) | |
| JP5824513B2 (ja) | 局所適用のための新規な相乗作用的医薬組成物 | |
| CA2241213A1 (fr) | Agent antiviral | |
| NO20076245L (no) | Anvendelse av TFPI for a behandle alvorlige bakterieinfeksjoner | |
| EP1200118B1 (fr) | Formulation pharmaceutique comprenant du megalatran et son promedicament | |
| US7232580B2 (en) | Use of extracts of Ginkgo biloba for preparing a medicament intended to treat sarcopenia | |
| WO2002048136A1 (fr) | Inhibiteurs de la proliferation des keratinocytes | |
| BR0213292A (pt) | tratamento de pneumonia severa por administração de inibidor da via de fator tecidual (tfpi) | |
| EP1940478B1 (fr) | Compositions pharmaceutiques servant a guerir des blessures et se presentant sous la forme d'une poudre sterile a base d'acides amines et de hyaluronate de sodium | |
| EP0679399A1 (fr) | L'utilisation des diesters phosphatiques pour le traitement des maladies prolifératives de l'épiderme | |
| EP0610336B1 (fr) | Traitement des troubles neurologiques a l'aide d'un compose inhibant l'interleukin-1 | |
| WO2002053153A1 (fr) | Medicaments permettant de traiter et de prevenir une douleur neurologique | |
| CN1341028A (zh) | 美拉加林的新用途 | |
| Iwamoto et al. | Acetyl-seryl-aspartyl-lysyl-proline is a novel natural cell cycle regulator of renal cells | |
| WO2018015976A1 (fr) | Nouvelle formule pour la cicatrisation rapide des plaies et le contrôle de l'infection | |
| RU2678309C1 (ru) | Применение антагонистов активируемых протеазой рецепторов 1 (par-1) для профилактики и/или лечения функциональных патологических состояний в области таза и промежности | |
| EP3189837B1 (fr) | Utilisations d'un composé flavonoïde dans la préparation d'une composition cicatrisante | |
| HUP0001097A2 (hu) | COMT-inhibitorok alkalmazása cukorbetegséggel kapcsolatos érrendszeri rendellenességek megelőzésére alkalmas gyógyszerkészítmények előállítására | |
| Wahl et al. | Ethanol‐induced inhibition of bone formation in a rat model of distraction osteogenesis: a role for the tumor necrosis factor signaling axis | |
| CN115778961B (zh) | Pd173074在制备抗瘙痒药物中的应用 | |
| KR20200051579A (ko) | 자가면역 미세혈관 장애의 치료 방법 | |
| TWI759633B (zh) | 突變角質細胞活性及預防皮膚癌化之薄荷精油 | |
| Lu et al. | Concurrent versus sequential combination of propranolol and dual‐wavelength laser (585 nm and 1064 nm) to treat complicated infantile hemangiomas |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: JP |