DOCSLIB.ORG

Compounds for Preventing Ototoxicity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Compounds for Preventing Ototoxicity (19) TZZ ¥ _T (11) EP 2 982 382 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 10.02.2016 Bulletin 2016/06 A61K 45/06 (2006.01) A61K 31/4174 (2006.01) A61K 31/4178 (2006.01) A61K 31/4196 (2006.01) (2006.01) (2006.01) (21) Application number: 14179771.2 A61K 31/427 A61P 27/16 (22) Date of filing: 04.08.2014 (84) Designated Contracting States: (72) Inventor: Gaboyard-Niay, Sophie AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 34770 Gigean (FR) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (74) Representative: Icosa Designated Extension States: 83 avenue Denfert-Rochereau BA ME 75014 Paris (FR) (71) Applicant: Sensorion 34000 Montpellier (FR) (54) Compounds for preventing ototoxicity (57) The present invention relates to a compound for use for preventing ototoxicity in a subject in need thereof. The present invention also relates to a composition, a pharmaceutical composition or a medicament comprising the compound of the invention. EP 2 982 382 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 982 382 A1 Description FIELD OF INVENTION 5 [0001] The present invention relates to methods for preventing ototoxicity. More specifically, the present invention relates to compounds for preventing ototoxicity, such as, for example, drug-induced ototoxicity. BACKGROUND OF INVENTION 10 [0002] There are several causes to ototoxicity: exposure to loud noise, head and neck radiation, but ototoxicity is more frequently caused by drug reactions. Ototoxic drugs include aminoglycoside antibiotics such as gentamicin, platinum- based chemotherapy agents such as cisplatin, excitatory neurotoxins such as glutamate, loop-diuretics, contaminants in food or medicaments or environmental and industrial pollutants. Symptoms of ototoxicity include partial or profound hearing loss, vertigo, tinnitus, and dizziness. If the ototoxic drug is used at high doses and/or for a prolonged time, the 15 impairments can become persistent and irreversible. [0003] Methods for treating ototoxicity were described in the art. For example, WO 2012/112810 and US 2011/0046156 describe the administration of multiparticulate corticosteroids and redox-active therapeutics respectively, for treating or reducing the severity of ototoxicity. However, the two of them only describe the treatment of a symptom of ototoxicity but do not prevent ototoxicity. 20 [0004] Some ototoxicity preventing agents are known, such as cimetidine, thiourea, pantoprazole or sodium thiosulfate. Cimetidine is an approved drug for the treatment of heartburn and peptic ulcers, but also has potential as a clinical antidote against cisplatin-induced nephrotoxicity. According to preclinical data, cimetidine also seems to have potential as a clinical antidote against cisplatin-induced ototoxicity. Unfortunately, this agent can lead to side effects because of the high therapeutically effective dose necessary to observe an effect. Besides WO 03061574 describes thiourea as an 25 ototoxic preventing agent. Moreover, as regards sodium thiosulfate, preliminary results from phase 3 studies seem to show a lower survival of administered patients (Freyer DR, "The effects of sodium thiosulfate (STS) on cisplatin-induced hearing loss: A report from the Children’s Oncology Group.", Abstract 10017. 2014 ASCO Annual Meeting). [0005] Therefore, to the Applicant knowledge, there is no clinically validated molecule for preventing ototoxicity, what- ever the cause thereof. Accordingly, there is still a need for means to prevent ototoxicity, i.e. an agent preventing the 30 appearance of ototoxicity or the worsening of ototoxicity. [0006] Antifungal agents are known to treat and prevent mycoses. Some of them were previously described to be non-ototoxic (Lawrence, The Laryngoscope, 2000; Munguia & Daniel, Int J Pediatr Otorhinolaryngol., 2008), and may therefore be used for treating otomycosis (i.e. mycosis of the ear). However, no direct effect of antifungal agents on ototoxicity was previously disclosed in the art. Surprisingly, the inventors showed that the administration of antifungal 35 agents allows preventing ototoxicity. [0007] The present invention thus provides compounds to prevent ototoxicity. SUMMARY 40 [0008] The present invention thus relates to a compound for use for preventing ototoxicity in a subject in need thereof, wherein said compound is an antifungal agent. [0009] In one embodiment, said compound is a compound of general formula I: 45 50 55 or a salt or solvate thereof, wherein 2 EP 2 982 382 A1 - X represents C or N atom; - Y represents nothing, O or S atom; - V represents nothing or an imino group; - V’ represents nothing or an imino group; 5 - n is 0, 1 or 2; - m is 0, 1 or 2; and - optionally, Z represents at least one halo, aryl, thiobenzyl or benzyl mercaptan group; preferably Z represents at least one halo group; more preferably Z represents at least one chloro or fluoro group; - R1 or R2 may be identical or different and each is independently selected from the group of H, hydroxyl, alkyl, 10 heteroalkyl, aryl, heteroaryl, alkylaryl, heteroalkylaryl, cycloether, oxolanyl, dioxolanyl or W1 group: 15 20 wherein, 25 + Y’ represents nothing, O or S atom; + n’ is 0, 1 or 2; + and optionally, Z’ represents at least one halo, aryl or benzyl mercaptan group; + Ra, Rb or Rc may be identical or different and each independently is selected from the group of H, aryl, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, alkoxy, alkyl, alkene, alkyne, cycloalkyl, cycloalkene, heteroalkyl, heter- 30 oaryl, heterocycloalkyl or halo group; preferably Ra, Rb or Rc is at least one halo group; more preferably is a chloro group; + Rb and Rc may represent one fused substituent selected from the group of aryl, heteroaryl, cycloalkyl, cycloalkane or heterocycloalkyl; optionally substituted by at least one group selected from halo, aryl, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, alkoxy, alkyl, alkene, alkyne, cycloalkyl, cycloalkene, heteroalkyl or heterocycloalkyl group; 35 preferably Rb and Rc represent an aryl group substituted by at least one chloro group; preferably R1 or R2 may be identical or different and each is independently a benzyl, phenyl, alkyltriazolo, triazolo, thiazolo, pyrimidinyl or quinazolinone group; optionally substituted by at least one group selected from halo, aryl, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, alkoxy, alkoxyaryl, alkyl, alkene, alkyne, cycloalkyl, cycloalkene, heteroalkyl, 40 heteroaryl, heteroalkylaryl, alkyletheraryl or heterocycloalkyl group; preferably a benzyl, phenyl, alkyltriazolo, triazolo, thiazolo, pyrimidinyl or quinazolinone group; said groups optionally substituted by at least one group selected from aryl, cycloalkyl, alkylaryl, alkylcycloalkyl, heteroaryl arylcycloalkyl, heterocycloalkyl, amidocycloalkyl or alkylamidocycloalkyl group; preferably benzyl, phenyl, alkyltriazolone, piperazinyl, arylpiperazinyl, alkylpiperazinyl, amidopiperazinyl or alky- lamidopiperazinyl group; optionally substituted by alkyl, nitrile, alkyltriazolone, hydroxylalkyltriazolone, piperazinyl, ami- 45 dopiperazinyl or alkylamidopiperazinyl; R2 is a nothing when V or V’ is an imido group or R1 is a cycloether, oxolanyl, dioxolanyl group; ----- refers to a single or a double bond, or said compound is thiabendazole, luliconazole or omoconazole. [0010] In one embodiment, said compound is a compound of general formula II: 50 55 3 EP 2 982 382 A1 5 10 15 or a salt or solvate thereof, wherein 20 - X is C or N atom; - V’ represents nothing or an imino group; - Y" represents nothing, O or S atom; - R1 is selected from the aryl group; preferably a phenyl or triazolo group optionally substituted by at least one halo 25 group, preferably by at least one chloro or fluoro group; - R2 is H, OH or nothing when V’ is an imino group; - Z represents at least one halo group, preferably at least one chloro or fluoro group; more preferably two chloro or fluoro groups; 30 ---- refers to a single or a double bond, preferably, the compound of formula II is selected from the list comprising miconazole, econazole, fluconazole, sulco- nazole and oxiconazole. [0011] In one embodiment, said compound is a compound of general formula III: 35 40 45 50 or a salt or solvate thereof, wherein 55 - X is C or N atom; - V’ represents nothing or an imino group; - Y" represents nothing, O or S atom; - R1 is selected from the aryl group; preferably a phenyl or triazolo group optionally substituted by at least one halo 4 EP 2 982 382 A1 group, preferably by at least one chloro or fluoro group; - R2 is H, OH or nothing when V’ is an imino group; - R3 and R4 are both chloro or fluoro group; 5 ---- refers to a single or a double bond, preferably, the compound of formula III is selected from the list comprising miconazole, econazole, fluconazole, sulco- nazole and oxiconazole. [0012] In one embodiment, said compound is a compound of general formula IV: 10 15 20 25 or a salt or solvate thereof, wherein R1 is a phenyl group optionally substituted by one or more chloro group, 30 preferably, the compound of formula IV is selected from the list comprising miconazole and econazole. [0013] In one embodiment, ototoxicity is induced: - by chemotherapeutic drugs, preferably selected from vincristine or platinum based chemotherapeutic agent, more 35 preferably cisplatin, carboplatin, oxiplatin or bis-platinate; - by antibiotic agents, preferably selected from aminoglycoside antibiotic or macrolide antibiotic; - by a diuretic; or - by salicylate. 40 [0014] In one embodiment, said ototoxicity
Load more

Recommended publications
  • (Schizotrypanum) Cruzi in Dog Hosts Paulo Marcos Da Matta Guedes,1 Julio A
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Nov. 2004, p. 4286–4292 Vol. 48, No. 11 0066-4804/04/$08.00ϩ0 DOI: 10.1128/AAC.48.11.4286–4292.2004 Copyright © 2004, American Society for Microbiology. All Rights Reserved. Activity of the New Triazole Derivative Albaconazole against Trypanosoma (Schizotrypanum) cruzi in Dog Hosts Paulo Marcos da Matta Guedes,1 Julio A. Urbina,2 Marta de Lana,3 Luis C. C. Afonso,1 Vanja M. Veloso,1 Washington L. Tafuri,1 George L. L. Machado-Coelho,4 Egler Chiari,5 and Maria Terezinha Bahia1* Departamento de Cieˆncias Biolo´gicas,1 Departamento de Ana´lises Clínicas,3 and Departamento de Farma´cia,4 Universidade Federal de Ouro Preto, Ouro Preto, and Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte,5 Minas Gerais, Brazil, and Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela2 Received 25 March 2004/Returned for modification 8 June 2004/Accepted 20 July 2004 Albaconazole is an experimental triazole derivative with potent and broad-spectrum antifungal activity and a remarkably long half-life in dogs, monkeys, and humans. In the present work, we investigated the in vivo activity of this compound against two strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas’ disease, using dogs as hosts. The T. cruzi strains used in the study were previously characterized (murine model) as susceptible (strain Berenice-78) and partially resistant (strain Y) to the drugs currently in clinical use, nifurtimox and benznidazole. Our results demonstrated that albaconazole is very effective in suppressing the proliferation of the parasite and preventing the death of infected animals.
    [Show full text]
  • List of Union Reference Dates A
    Active substance name (INN) EU DLP BfArM / BAH DLP yearly PSUR 6-month-PSUR yearly PSUR bis DLP (List of Union PSUR Submission Reference Dates and Frequency (List of Union Frequency of Reference Dates and submission of Periodic Frequency of submission of Safety Update Reports, Periodic Safety Update 30 Nov. 2012) Reports, 30 Nov.
    [Show full text]
  • Lamisil Versus Clotrimazole in the Treatment of Vulvovaginal Candidiasis
    Volume 5 Number 1 (March 2013) 86-90 Lamisil versus clotrimazole in the treatment of vulvovaginal candidiasis Ali Zarei Mahmoudabadi1,2, Mahin Najafyan3, Eskandar Moghimipour4, Maryam Alwanian1, Zahra Seifi1 1Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2Infectious Diseases and Tropical Medicine Centre, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 3Department of Obstetric and Genecology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 4Department of Pharmaceutics, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Received: March 2012, Accepted: October 2012. ABSTRACT Background and Objectives: Vaginal candidiasis is a common disease in women during their lifetime and occurs in diabetes patients, during pregnancy and oral contraceptives users. Although several antifungals are routinely used for treatment; however, vaginal candidiasis is a challenge for patients and gynecologists. The aim of the present study was to evaluate terbinafine (Lamisil) on Candida vaginitis versus clotrimazole. Materials and Methods: In the present study women suspected to have vulvovaginal candidiasis were sampled and disease confirmed using direct smear and culture examination from vaginal discharge. Then, patients were randomly divided into two groups, the first group (32 cases) was treated with clotrimazole and the next (25 cases) with Lamisil. All patients were followed-up to three weeks of treatment and therapeutic effects of both antifungal were compared. Results: Our results shows that 12 (37.5%) patients were completely treated with clotrimazole during two weeks and, 6(18.8%) patients did not respond to drugs and were refereed for fluconazole therapy. Fourteen (43.8%) patients showed moderate response and clotrimazole therapy was extended for one more week.
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • WO 2014/195872 Al 11 December 2014 (11.12.2014) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/195872 Al 11 December 2014 (11.12.2014) P O P C T (51) International Patent Classification: (74) Agents: CHOTIA, Meenakshi et al; K&S Partners | Intel A 25/12 (2006.01) A61K 8/11 (2006.01) lectual Property Attorneys, 4121/B, 6th Cross, 19A Main, A 25/34 (2006.01) A61K 8/49 (2006.01) HAL II Stage (Extension), Bangalore 560038 (IN). A01N 37/06 (2006.01) A61Q 5/00 (2006.01) (81) Designated States (unless otherwise indicated, for every A O 43/12 (2006.01) A61K 31/44 (2006.01) kind of national protection available): AE, AG, AL, AM, AO 43/40 (2006.01) A61Q 19/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A01N 57/12 (2006.01) A61K 9/00 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, AOm 59/16 (2006.01) A61K 31/496 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/IB20 14/06 1925 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (22) International Filing Date: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 3 June 2014 (03.06.2014) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • A Ketoconazole Susceptibility Test for Malassezia Pachydermatis Using Modified Leeming–Notman Agar
    Journal of Fungi Article A Ketoconazole Susceptibility Test for Malassezia pachydermatis Using Modified Leeming–Notman Agar Bo-Young Hsieh 1,2, Wei-Hsun Chao 3, Yi-Jing Xue 2 and Jyh-Mirn Lai 2,* 1 Lugu Township Administration, Nanto County 55844, Taiwan; [email protected] 2 College of Veterinary Medicine, National Chiayi University, No. 580, XinMin Rd., Chiayi City 60054, Taiwan; [email protected] 3 Department of Hospitality Management, WuFung University, Chiayi City 60054, Taiwan; [email protected] * Correspondence: [email protected]; Tel.: +886-5-2732920; Fax: +886-5-2732917 Received: 18 September 2018; Accepted: 14 November 2018; Published: 16 November 2018 Abstract: The aim of this study was to establish a ketoconazole susceptibility test for Malassezia pachydermatis using modified Leeming–Notman agar (mLNA). The susceptibilities of 33 M. pachydermatis isolates obtained by modified CLSI M27-A3 method were compared with the results by disk diffusion method, which used different concentrations of ketoconazole on 6 mm diameter paper disks. Results showed that 93.9% (31/33) of the minimum inhibitory concentration (MIC) values obtained from both methods were similar (consistent with two methods within 2 dilutions). M. pachydermatis BCRC 21676 and Candida parapsilosis ATCC 22019 were used to verify the results obtained from the disk diffusion and modified CLSI M27-A3 tests, and they were found to be consistent. Therefore, the current study concludes that this new novel test—using different concentrations of reagents on cartridge disks to detect MIC values against ketoconazole—can be a cost-effective, time-efficient, and less technically demanding alternative to existing methods.
    [Show full text]
  • WO 2015/134796 Al 11 September 2015 (11.09.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/134796 Al 11 September 2015 (11.09.2015) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 9/14 (2006.01) A61K 47/10 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 9/16 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/US20 15/0 19042 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 5 March 2015 (05.03.2015) 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. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 61/948,173 5 March 2014 (05.03.2014) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, 14/307,138 17 June 2014 (17.06.2014) US TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (71) Applicant: PROFESSIONAL COMPOUNDING CEN¬ LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, TERS OF AMERICA [US/US]; 9901 South Wilcrest SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Drive, Houston, TX 77099 (US).
    [Show full text]
  • Dermatologic Medication in Pregnancy
    Marušić et al. Acta Dermatovenerol Croat Subcutaneous dirofilariasis Acta Dermatovenerol Croat 2009;17(1):40-47 REVIEW Dermatologic Medication in Pregnancy Petra Turčić1, Zrinka Bukvić Mokos2, Ružica Jurakić Tončić2, Vladimir Blagaić3, Jasna Lipozenčić2 1School of Pharmacy and Biochemistry, University of Zagreb; 2University Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine; 3University Department of Obstetrics and Gynecology, Sveti Duh General Hospital, Zagreb, Croatia Corresponding author: SUMMARY In female body, a vast number of skin changes occur Petra Turčić, Phar. M. during pregnancy. Some of them are quite distressing to many women. Department of Pharmacology Therefore, performing treatment for physiologic skin changes during pregnancy with antiinfective agents, glucocorticosteroids, topical School of Pharmacy and Biochemistry immunomodulators, retinoids, minoxidil, etc., is discussed. Drug University of Zagreb administration during pregnancy must be reasonable. Domagojeva 2 KEY WORDS: dermatologic medication, pregnancy, physiologic skin HR-10000 Zagreb changes, treatment Croatia [email protected] Received: September 1, 2008 Accepted: January 9, 2009 INTRODUCTION In female body, a vast number of changes oc- bolic imbalances (3), diabetes and cardiovascular cur during pregnancy. Some of them are quite diseases (4). Pregnancy extends and alters the distressing to many women. Therefore, perform- impact of sex differences on absorption, distribu- ing treatment for these changes during pregnancy tion, metabolism and elimination (5). Cardiac out- is discussed. Normal pregnancy needs to avoid put is elevated early and remains elevated for the harmful drugs, both prescribed and over-the coun- remainder of pregnancy. Regional blood flow can ter, and drugs of abuse, including cigarettes, alco- change, with some areas of the skin having sub- hol as well as occupational and environmental ex- stantial increases in blood flow during the course posure to potentially harmful chemicals.
    [Show full text]
  • WO 2018/102407 Al 07 June 2018 (07.06.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/102407 Al 07 June 2018 (07.06.2018) W !P O PCT (51) International Patent Classification: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, C07K 7/60 (2006.01) G01N 33/53 (2006.01) EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, CI2Q 1/18 (2006.01) 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, (21) International Application Number: KM, ML, MR, NE, SN, TD, TG). PCT/US2017/063696 (22) International Filing Date: Published: 29 November 201 7 (29. 11.201 7) — with international search report (Art. 21(3)) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/427,507 29 November 2016 (29. 11.2016) US 62/484,696 12 April 2017 (12.04.2017) US 62/53 1,767 12 July 2017 (12.07.2017) US 62/541,474 04 August 2017 (04.08.2017) US 62/566,947 02 October 2017 (02.10.2017) US 62/578,877 30 October 2017 (30.10.2017) US (71) Applicant: CIDARA THERAPEUTICS, INC [US/US]; 63 10 Nancy Ridge Drive, Suite 101, San Diego, CA 92121 (US). (72) Inventors: BARTIZAL, Kenneth; 7520 Draper Avenue, Unit 5, La Jolla, CA 92037 (US). DARUWALA, Paul; 1141 Luneta Drive, Del Mar, CA 92014 (US). FORREST, Kevin; 13864 Boquita Drive, Del Mar, CA 92014 (US).
    [Show full text]
  • Fungal Infections (Mycoses): Dermatophytoses (Tinea, Ringworm)
    Editorial | Journal of Gandaki Medical College-Nepal Fungal Infections (Mycoses): Dermatophytoses (Tinea, Ringworm) Reddy KR Professor & Head Microbiology Department Gandaki Medical College & Teaching Hospital, Pokhara, Nepal Medical Mycology, a study of fungal epidemiology, ecology, pathogenesis, diagnosis, prevention and treatment in human beings, is a newly recognized discipline of biomedical sciences, advancing rapidly. Earlier, the fungi were believed to be mere contaminants, commensals or nonpathogenic agents but now these are commonly recognized as medically relevant organisms causing potentially fatal diseases. The discipline of medical mycology attained recognition as an independent medical speciality in the world sciences in 1910 when French dermatologist Journal of Raymond Jacques Adrien Sabouraud (1864 - 1936) published his seminal treatise Les Teignes. This monumental work was a comprehensive account of most of then GANDAKI known dermatophytes, which is still being referred by the mycologists. Thus he MEDICAL referred as the “Father of Medical Mycology”. COLLEGE- has laid down the foundation of the field of Medical Mycology. He has been aptly There are significant developments in treatment modalities of fungal infections NEPAL antifungal agent available. Nystatin was discovered in 1951 and subsequently and we have achieved new prospects. However, till 1950s there was no specific (J-GMC-N) amphotericin B was introduced in 1957 and was sanctioned for treatment of human beings. In the 1970s, the field was dominated by the azole derivatives. J-GMC-N | Volume 10 | Issue 01 developed to treat fungal infections. By the end of the 20th century, the fungi have Now this is the most active field of interest, where potential drugs are being January-June 2017 been reported to be developing drug resistance, especially among yeasts.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • Vr Meds Ex01 3B 0825S Coding Manual Supplement Page 1
    vr_meds_ex01_3b_0825s Coding Manual Supplement MEDNAME OTHER_CODE ATC_CODE SYSTEM THER_GP PHRM_GP CHEM_GP SODIUM FLUORIDE A12CD01 A01AA01 A A01 A01A A01AA SODIUM MONOFLUOROPHOSPHATE A12CD02 A01AA02 A A01 A01A A01AA HYDROGEN PEROXIDE D08AX01 A01AB02 A A01 A01A A01AB HYDROGEN PEROXIDE S02AA06 A01AB02 A A01 A01A A01AB CHLORHEXIDINE B05CA02 A01AB03 A A01 A01A A01AB CHLORHEXIDINE D08AC02 A01AB03 A A01 A01A A01AB CHLORHEXIDINE D09AA12 A01AB03 A A01 A01A A01AB CHLORHEXIDINE R02AA05 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S01AX09 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S02AA09 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S03AA04 A01AB03 A A01 A01A A01AB AMPHOTERICIN B A07AA07 A01AB04 A A01 A01A A01AB AMPHOTERICIN B G01AA03 A01AB04 A A01 A01A A01AB AMPHOTERICIN B J02AA01 A01AB04 A A01 A01A A01AB POLYNOXYLIN D01AE05 A01AB05 A A01 A01A A01AB OXYQUINOLINE D08AH03 A01AB07 A A01 A01A A01AB OXYQUINOLINE G01AC30 A01AB07 A A01 A01A A01AB OXYQUINOLINE R02AA14 A01AB07 A A01 A01A A01AB NEOMYCIN A07AA01 A01AB08 A A01 A01A A01AB NEOMYCIN B05CA09 A01AB08 A A01 A01A A01AB NEOMYCIN D06AX04 A01AB08 A A01 A01A A01AB NEOMYCIN J01GB05 A01AB08 A A01 A01A A01AB NEOMYCIN R02AB01 A01AB08 A A01 A01A A01AB NEOMYCIN S01AA03 A01AB08 A A01 A01A A01AB NEOMYCIN S02AA07 A01AB08 A A01 A01A A01AB NEOMYCIN S03AA01 A01AB08 A A01 A01A A01AB MICONAZOLE A07AC01 A01AB09 A A01 A01A A01AB MICONAZOLE D01AC02 A01AB09 A A01 A01A A01AB MICONAZOLE G01AF04 A01AB09 A A01 A01A A01AB MICONAZOLE J02AB01 A01AB09 A A01 A01A A01AB MICONAZOLE S02AA13 A01AB09 A A01 A01A A01AB NATAMYCIN A07AA03 A01AB10 A A01
    [Show full text]