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METHOD FOR TESTING LEUKODERMA TOXICITY AND MELANOSIS TOXICITY

Foreign code F170009300
File No. (S2016-0771-N0)
Posted date Dec 14, 2017
Country WIPO
International application number 2017JP017957
International publication number WO 2017203999
Date of international filing May 11, 2017
Date of international publication Nov 30, 2017
Priority data
  • P2016-104698 (May 25, 2016) JP
Title METHOD FOR TESTING LEUKODERMA TOXICITY AND MELANOSIS TOXICITY
Abstract The present invention addresses the problem of providing an evaluation method that can evaluate leukoderma toxicity or melanosis toxicity at high sensitivities. Provided is a leukoderma toxicity test method comprising a step for applying a test substance to the tail of a hairless mouse that can produce melanin, and a step for evaluating the presence/absence and/or degree of induction of leukoderma on the tail of the hairless mouse and scoring the leukoderma toxicity of the test substance on the basis of the results of the evaluation.
Scope of claims [claim1]
1. Step below (1) and (2) is included, facula poisonous method of exam:
(1) the step which applies the suffering substance to the tail of the hair less mouse which possesses melanin production talent,
(2) the step which presence of inducement of the facula in the tail of the aforementioned hair less mouse and/or you appraise, decides the facula virulence of the suffering substance on the basis of the appraisal result.
[claim2]
2. The aforementioned hair less mouse, is the hair less mouse whose melanin production talent is normal, in claim 1 method of exam of statement.
[claim3]
3. The genetic background of the aforementioned hair less mouse is C57BL/6, in claim 1 method of exam of statement.
[claim4]
4. The aforementioned hair less mouse, the activated type RET gene the gene is introduced RET/which (o) - in toransujienitsukumausu, the genetic background resetting the hair less mouse of C57BL/6 in hetero type and breeding and the hair less RET mouse or the said mouse which can, the sibling breeding it is the hair less RET mouse which can, in claim 3 method of exam of statement.
[claim5]
5. The aforementioned genetic background the hair less mouse of C57BL/6, Hos: Resetting the C57BL/6 mouse to the HRM hair less mouse and breeding and the mouse or the said mouse which can, the sibling breeding it is the mouse which can, in claim 4 method of exam of statement.
[claim6]
6. Step below (1) and (2) is included, melanosis poisonous method of exam:
(1) the activated type RET gene the gene is introduced RET/which (o) - in toransujienitsukumausu, the genetic background resetting the hair less mouse of C57BL/6 in hetero type and breeding and the hair less RET mouse or the said mouse which can, the sibling breeding the skin of the hair less RET mouse which can (however, you exclude the skin of the tail) the step which applies the suffering substance,
(2) the step which presence of inducement of the melanosis in the aforementioned skin of the aforementioned hair less RET mouse and/or you appraise, decides the melanosis virulence of the suffering substance on the basis of the appraisal result.
[claim7]
7. The aforementioned skin the back, is the stomach or the head the skin, in claim 6 method of exam of statement.
[claim8]
8. The step (1)-(3) below is included, facula virulence and melanosis poisonous simultaneous method of exam:
(1) the activated type RET gene the gene is introduced RET/which (o) - in toransujienitsukumausu, the genetic background resetting the hair less mouse of C57BL/6 in hetero type and breeding and the hair less RET mouse or the said mouse which can, the sibling breeding the tail and the skin of the hair less RET mouse which can (however, you exclude the skin of the tail) with the step which applies the suffering substance,
(2) the step which presence of inducement of the facula in the tail of the aforementioned hair less RET mouse and/or you appraise, decides the facula virulence of the suffering substance on the basis of the appraisal result,
(3) the step which presence of inducement of the melanosis in the aforementioned skin of the aforementioned hair less RET mouse and/or you appraise, decides the melanosis virulence of the suffering substance on the basis of the appraisal result.
[claim9]
9. The aforementioned skin the back, is the stomach or the head the skin, in claim 8 method of exam of statement.
[claim10]
10. The aforementioned activated type RET gene it is the RFP-RET gene which it occurs with the hybrid of the c-RET gene and the RFP gene, claim 4, either of the 6-9 in one section method of exam of statement.
[claim11]
11. The aforementioned activated type RET gene is connected to the metarochionein I promoter, claim 4, either of the 6-10 in one section method of exam of statement.
[claim12]
12. The description above RET/(o) - toransujienitsukumausu, 192 systems RET/(o) - toransujienitsukumausu and 242 systems RET/(o) - toransujienitsukumausu and 304 systems RET/(o) - toransujienitsukumausu or 304/B6 system RET/(o) - is toransujienitsukumausu, claim 4, either of the 6-11 in one section method of exam of statement.
[claim13]
13. It consists of (i) below or the mouse (ii), facula poisonously and melanosis poisonously the mouse of sensitivity:
(i) The hair less RET mouse where the activated type RET gene the gene is introduced RET/which (o) - in toransujienitsukumausu, the genetic background you reset the hair less mouse of C57BL/6 in hetero type and breed and can,
(ii) (i) The sibling breeding the mouse, the hair less RET mouse which can.
[claim14]
14. The aforementioned activated type RET gene it is the RFP-RET gene which it occurs with the hybrid of the c-RET gene and the RFP gene, in claim 13 the sensitivity mouse of statement.
[claim15]
15. The aforementioned activated type RET gene is connected to the metarochionein I promoter, in claim 13 or 14 the sensitivity mouse of statement.
[claim16]
16. The description above RET/(o) - toransujienitsukumausu, 192 systems RET/(o) - toransujienitsukumausu and 242 systems RET/(o) - toransujienitsukumausu and 304 systems RET/(o) - toransujienitsukumausu or 304/B6 system RET/(o) - is toransujienitsukumausu, either of the claim 13-15 in one section the sensitivity mouse of statement.
[claim17]
17. The in vitro method of exam which features that facula virulence of the suffering substance is appraised meranosaito which is picked from the tail of the hair less mouse which possesses melanin production talent or making use of that passage of generations cell.
[claim18]
18. The activated type RET gene the gene is introduced RET/which (o) - in toransujienitsukumausu, the genetic background resetting the hair less mouse of C57BL/6 in hetero type and breeding and the hair less RET mouse or the said mouse which can, the sibling breeding the skin of the hair less RET mouse which can (however, you exclude the skin of the tail) from meranosaito which is picked or making use of that passage of generations cell, in vitro method of exam which features that you appraise the melanosis virulence of the suffering substance.
[claim19]
19. Step below (a) the - (d) it includes, facula virulence and/or in vitro method of exam in order to appraise melanosis virulence:
(A) The activated type RET gene the gene is introduced RET/which (o) - in toransujienitsukumausu, the genetic background resetting the hair less mouse of C57BL/6 in hetero type and breeding and the hair less RET mouse or the said mouse which can, the sibling breeding the step which prepares the sample which includes skin meranosaito of the hair less RET mouse which can divides into the test group and the contrast group,
(B) The step which cultures the test group under existing of the suffering substance,
(C) Step (b) other than the thing where the test group and the suffering substance after are under non existing concerning the contrast group which was cultured under identical conditions, c-Met, RFP-RET, c-Ret and Enothelin receptor B (Ednrb), c-kit, Mc1r, Mitf-m, Tyrosinase, Tyrosinase-realted protein-2 and TGF-beta type receptor 2 (Tgfr2), Fibroblast growth factor (Fgfr), Bcl2, p53, survivin and CCAAT-enhancer-binding protein homologous protein (CHOP), Glutamate cystein ligase (GCLC) and NF-E2 related factor2 (Nrf2), HEAT shock protein (HSP) 70, Foxp1, Foxp3, CCR6, Bach2 and NACHT leucine-rich-repeat protein 1 (Nalp), Cytotoxic T-lymphocyte antigen-4 (Ctla4) and Granzyme B (GZMB) from the group which consists of the step which detects the revelation or activity of the marker molecule of one or more which is selected,
(D) The step which compares the detection result between the test group and the contrast group, on the basis of the relative result facula virulence of the suffering substance and/or decides melanosis virulence.
[claim20]
20. Step (A)-(D) below is included, facula virulence and/or in vitro method of exam in order to appraise melanosis virulence:
The step where (A) the activated type RET gene the gene is introduced RET/which (o) - prepares the meranosaito cell stocks of toransujienitsukumausu origin in hetero type, divides into the test group and the contrast group,
(B) the step which cultures the test group under existing of the suffering substance,
(C) step (B) other than the thing where the test group and the suffering substance after are under non existing concerning the contrast group which was cultured under identical conditions, c-Met, RFP-RET, c-Ret and Enothelin receptor B (Ednrb), c-kit, Mc1r, Mitf-m, Tyrosinase, Tyrosinase-realted protein-2 and TGF-beta type receptor 2 (Tgfr2), Fibroblast growth factor (Fgfr), Bcl2, p53, survivin and CCAAT-enhancer-binding protein homologous protein (CHOP), Glutamate cystein ligase (GCLC) and NF-E2 related factor2 (Nrf2), HEAT shock protein (HSP) 70, Foxp1, Foxp3, CCR6, Bach2 and NACHT leucine-rich-repeat protein 1 (Nalp), Cytotoxic T-lymphocyte antigen-4 (Ctla4) and Granzyme B(GZMB) From the group which consists of the step which detects the revelation or activity of the marker molecule of one or more which is selected,
The step which (D) compares the detection result between the test group and the contrast group, on the basis of the relative result facula virulence of the suffering substance and/or decides melanosis virulence.
[claim21]
21. Step below (a) the - (c) it includes, prevention or remedy of the facula screening method of the medicine:
(A) The step which administers facula inducement processing to the tail of the hair less mouse which possesses melanin production talent,
(B) The step which prescribes the suffering substance to the aforementioned hair less mouse,
(C) The step which decides the preventive effect or the curative effect of the suffering substance.
[claim22]
22. Step (A)-(C) below is included, prevention or remedy of the melanosis screening method of the medicine:
(A) the activated type RET gene the gene is introduced RET/which (o) - in toransujienitsukumausu, the genetic background resetting the hair less mouse of C57BL/6 in hetero type and breeding and the hair less RET mouse or the said mouse which can, the sibling breeding the skin of the hair less RET mouse which can (however, you exclude the skin of the tail) the step which administers melanosis inducement processing,
(B) the step which prescribes the suffering substance to the aforementioned hair less RET mouse,
(C) the step which decides the preventive effect or the curative effect of the suffering substance.
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NAGOYA UNIVERSITY
  • Inventor
  • KATO MASASHI
  • IIDA MACHIKO
IPC(International Patent Classification)
Specified countries (WO2017203999)
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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