DOCSLIB.ORG

Novel Composition for Treating Metabolic Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Novel Composition for Treating Metabolic Syndrome (19) & (11) EP 2 494 967 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 05.09.2012 Bulletin 2012/36 A61K 31/155 (2006.01) A61K 31/60 (2006.01) A61K 45/06 (2006.01) A61K 31/4045 (2006.01) (21) Application number: 12170283.1 (22) Date of filing: 16.01.2008 (84) Designated Contracting States: (72) Inventor: Chen, Chien-Hung AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Forest Hills, NY New York 11375 (US) HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR (74) Representative: Coehn, Markus Fish & Richardson P.C. (30) Priority: 16.01.2007 US 885212 P Mies-van-der-Rohe-Strasse 8 80807 München (DE) (62) Document number(s) of the earlier application(s) in accordance with Art. 76 EPC: Remarks: 08727718.2 / 2 118 279 This application was filed on 31-05-2012 as a divisional application to the application mentioned (71) Applicant: IPINTL, LLC under INID code 62. Flushing, NY 11354 (US) (54) Novel composition for treating metabolic syndrome (57) The invention relates to a composition that in- kinase (AMPK) activator; a second agent that possesses cludes a first agent selected from the group consisting anti-inflammatory activity; and a third agent that possess- of an oxidative phosphorylation inhibitor, an ionophore, es serotonin activity. and an adenosine 5’-monophosphate-activated Protein EP 2 494 967 A1 Printed by Jouve, 75001 PARIS (FR) 1 EP 2 494 967 A1 2 Description serotonin (e.g., serotonin sulfate, a serotonin creatinine sulfate complex, or serotonin hydrochloride) and a sero- CROSS-REFERENCE TO RELATED APPLICATION tonin re-uptake inhibitor. A preferred composition con- tains metformin hydrochloride, aspirin, and a serotonin [0001] This application claims the benefit of US Provi- 5 creatinine sulfate complex. The three agents mentioned sional Application 60/885,212, filed January 16, 2007, above can treat the target diseases via biological mech- the content of which is incorporated herein by reference anisms other than those described therein. For example, in its entirety. metformin may treat a target disease (e.g., diabetes) via a mechanism other than inhibiting oxidative phosphor- BACKGROUND 10 ylation or activating AMPK. [0005] In another aspect, the invention features a com- [0002] Metabolic syndrome is characterized by a position consisting essentially of a first agent that can be group of metabolic risk factors, including abdominal an oxidative phosphorylation inhibitor, an ionophore, or obesity, atherogenic dyslipidemia (e.g., high triglyceride an AMPK activator, a second agent that possesses anti- levels, low HDL cholesterol levels, and high LDL choles- 15 inflammatory activity, and a third agent that possesses terol levels), hypertension, insulin resistance, prothrom- serotonin activity. The term "consisting essentially of" botic state (e.g., high fibrinogen or plasminogen activator used herein limits a composition to the three specified inhibitor-1 levels), and proinflammatory state (e.g., ele- agents and those that do not materially affect its basic vated C-reactive protein levels). Metabolic syndrome has and novel characteristics, i.e., the efficacy in treating a become increasingly common in the United States. It is 20 target disease described herein. An example of such a estimated that over 50 million Americans have this dis- composition contains the above- mentioned three agents order. There is a need to develop novel drugs to effec- and a pharmaceutically acceptable carrier. tively treat this disorder. [0006] The compositions described above can contain 5-5,000 mg (e.g., 5-3,000 mg, 5-1,500 mg or 5-1,000 mg) SUMMARY 25 of the first agent, 1-5,000 mg (e.g., 1-3000 mg, 1-1,000 mg, 1-500 mg, or 1-100 mg) of the second agent, and [0003] This invention is based on the unexpected dis- 0.1-1,000 mg (e.g., 0.1-100 mg, 0.1-50 mg, or 0.1-30 mg) covery that a combination of certain known drugs exhibits of the third agent, or in quantities of the same ratio as synergistic effects in treating metabolic syndrome and that calculated based on the above amounts. various other diseases. 30 [0007] In still another aspect, this invention features a [0004] In one aspect, the invention features a compo- method for treating metabolic syndrome, Parkinson’s dis- sition that includes a first agent that can be an oxidative ease, or polycystic ovarian syndrome. The method in- phosphorylation inhibitor, an ionophore, or an adenosine cludes administering to a subj ect in need thereof an ef- 5’-monophosphate-activated Protein kinase (AMPK) ac- fective amount of one or more of the compositions de- tivator, a second agent that possesses anti- inflammatory 35 scribed above. The diseases mentioned above also in- activity, and a third agent that possesses or maintains clude their associated disorders. For example, disorders serotonin activity. The term "oxidative phosphorylation associated with metabolic syndrome include atheroscle- inhibitor" refers to any suitable agents that inhibit oxida- rosis, coronary heart disease, stroke, obesity, diabetes, tive phosphorylation, such as oxidative phosphorylation atherogenic dyslipidemia (e.g., high triglyceride levels, uncouplers. An ionophore is a lipid- soluble molecule ca- 40 low HDL cholesterol levels, and high LDL cholesterol lev- pable of transporting an ion across the lipid bilayer of cell els), hypertension, insulin resistance, prothrombotic membranes; and an AMPK activator is an agent that ac- state (e.g., high fibrinogen or plasminogen activator in- tivates AMPK to phosphorylate its substrates, e.g., hibitor-1 levels), and proinflammatory state (e.g., elevat- acetyl-CoA carboxylase and malonyl-CoA decarboxyla- ed C-reactive protein levels). se. Examples of the first agent include metformin (e.g., 45 [0008] The term "treating" or "treatment" used herein metformin chloride), phenformin, buformin, ephedrine, refers to administering one or more above-described thyroxine, salicylanilide, and salicylic acid. The second compositions to a subject, who has a disease described agent can be any suitable anti- inflammatory compounds above, a symptom of such a disease, or a predisposition (e.g., non-steroidal anti-inflammatory compounds). Ex- toward such a disease, with the purpose to confer a ther- amples include aspirin, diclofenac (e.g., diclofenac po- 50 apeutic effect, e.g., to cure, relieve, alter, affect, amelio- tassium or diclofenac sodium), ibuprofen (e.g., dexibu- rate, or prevent the disease, the symptom of it, or the profen or dexibuprofen lysine), indomethacin, acetami- predisposition toward it. nophen, nimesulide, and a COX-2 inhibitor (e.g., a nitric [0009] The composition described above can be in dry oxide-based COX-2 inhibitor). The third agent can be a form (e.g., powder or tablet) or in aqueous form (e.g., compound possessing or maintaining at least one of the 55 beverage or syrup). It can be a dietary supplement or a serotonin’s activities and, when used in combination with pharmaceutical formulation (containing a pharmaceuti- the first and second agents, effectively treats one or more cally acceptable carrier). It can also be a drink or a food the target diseases of this invention. Examples includes product. Examples include tea (e.g., a tea drink and the 2 3 EP 2 494 967 A1 4 contents of a tea bag), soft drinks, juice (e.g., a fruit ex- 2,4-bis(p-chloroanilino)pyrimidine, glyceraldehyde-3- tract and a juice drink), milk, coffee, cookies, cereals, phosphate dehydrogenase, oligomycin, tributyltin chlo- chocolates, and snack bars. ride, aurovertin, rutamycin, venturicidin, mercurials, di- [0010] The first, second, and third agents described cyclohexylcarbdiimide, Dio-9, m-chlorophenyl-hydrazo- above include active compounds, as well as their salts, 5 ne mesoxalonitrile, ionomycin, calcium ionophores (e.g., prodrugs, and solvates, if applicable. A salt, for example, A23187, NMDA, CA 1001, or enniatin B), compounds can be formed between an anion and a positivelycharged that increase the Ca+2 concentration in mitochondria group (e.g., amino) on an agent. Suitable anions include (e.g., atractyloside, bongkrekic acid, thapsigargin, amino chloride, bromide, iodide, sulfate, nitrate, phosphate, ci- acid neurotransmitters, glutamate, N-methyl-D-aspartic trate, methanesulfonate, trifluoroacetate, acetate, chlo- 10 acid, carbachol, ionophores, inducers of potassium de- rophenyoxyacetate, malate, tosylate, tartrate, fumarate, polarization), apoptogens (i.e., compounds that induce glutamate, glucuronate, lactate, glutarate, benzoate, em- apoptosis), valinomycin, gramicidin, nonactin, nigericin, bonate, glycolate, pamoate, aspartate, parachlorophe- lasalocid, and monensin. The first agent can be an AMPK noxyisobutyrate, formate, succinate, cyclohexanecar- activator (e.g., metfomin or phenformin, buformin, AIC- boxylate, hexanoate, octonoate, decanoate, hexade-15 AR, thienopyridones, resveratrol, nootkatone, thiazole, canoate, octodecanoate, benzenesulphonate, trimeth- or adiponectin) oxybenzoate, paratoluenesulphonate, adamantanecar- [0015] The second agent can include steroidal anti- boxylate, glycoxylate, pyrrolidonecarboxylate, naphtha- inflammatory drugs and non-steroidal anti-inflammatory lenesulphonate, 1-glucosephosphate, sulphite, dithion- drugs. Examples of steroidal anti- inflammatory drugs in- ate, and maleate. Likewise, a salt can also be formed 20 clude glucocorticoids, hydrocortisone, cortisone, beclo- between a cation and a negatively charged group (e.g., methasone, dipropionate, betamethasone, dexametha- carboxylate) on an agent. Suitable cations
Load more

Recommended publications
  • Comparing the Effects of Salts of Diclofenac and Almioprofen with Aspirin on Serum Electrolytes, Creatinine and Urea Levels in Rabbits
    Comparing the effects of salts of diclofenac and almioprofen with aspirin on serum electrolytes, creatinine and urea levels in rabbits Nawazish-i-Husain Syed*, Farnaz Zehra, Amir Ali Rizvi Syed, Sabiha Karim and Farrakh Zia Khan University College of Pharmacy, University of the Punjab, Lahore, Pakistan Abstract: The effects of diclofenac sodium, diclofenac potassium, alminoprofen and aspirin on serum electrolytes (serum Na+ and K+), urea and creatinine were compared in rabbits in acute and chronic phases of treatment. The data suggested that all the four drugs markedly increased the serum electrolytes, urea and creatinine levels in both post- treatment phases. In conclusion, present study does not present any advantage of diclofenac sodium over diclofenac potassium at electrolyte levels on short and long term treatment. Nevertheless, current data support the evidence of renal function impairment by all the four drug therapies used in the present study, which is generally caused by NSAIDS. Keywords: NSAIDs, renal function, serum electrolytes. INTRODUCTION were given fodder twice daily, while water was available ad libitum. Throughout the study, environmental Inflammatory diseases including rheumatoid arthritis and conditions remained constant. Rabbits were divided into osteoarthritis are initially treated with non-steroidal anti- five groups, each of six animals. Same group of animals inflammatory drugs (NSAIDS) (Patrono and Rocca, were used for acute and chronic phases of the study. In 2009). Previously, steroids were prescribed to manage the both studies, rabbits of each group were orally chronic inflammatory diseases, however, due to their administered diclofenac Na+, diclofenac K+, severe adverse effects, NSAIDS has become the first alminoprofen, acetyl salicylic acid in a doses of 2.5mg, choice to treat these diseases.
    [Show full text]
  • Table S1: Sensitivity, Specificity, PPV, NPV, and F1 Score of NLP Vs. ICD for Identification of Symptoms for (A) Biome Developm
    Table S1: Sensitivity, specificity, PPV, NPV, and F1 score of NLP vs. ICD for identification of symptoms for (A) BioMe development cohort; (B) BioMe validation cohort; (C) MIMIC-III; (D) 1 year of notes from patients in BioMe calculated using manual chart review. A) Fatigue Nausea and/or vomiting Anxiety Depression NLP (95% ICD (95% CI) P NLP (95% CI) ICD (95% CI) P NLP (95% CI) ICD (95% CI) P NLP (95% CI) ICD (95% CI) P CI) 0.99 (0.93- 0.59 (0.43- <0.00 0.25 (0.12- <0.00 <0.00 0.54 (0.33- Sensitivity 0.99 (0.9 – 1) 0.98 (0.88 -1) 0.3 (0.15-0.5) 0.85 (0.65-96) 0.02 1) 0.73) 1 0.42) 1 1 0.73) 0.57 (0.29- 0.9 (0.68- Specificity 0.89 (0.4-1) 0.75 (0.19-1) 0.68 0.97 (0.77-1) 0.03 0.98 (0.83-1) 0.22 0.81 (0.53-0.9) 0.96 (0.79-1) 0.06 0.82) 0.99) 0.99 (0.92- 0.86 (0.71- 0.94 (0.79- 0.79 (0.59- PPV 0.96 (0.82-1) 0.3 0.95 (0.66-1) 0.02 0.95 (0.66-1) 0.16 0.93 (0.68-1) 0.12 1) 0.95) 0.99) 0.92) 0.13 (0.03- <0.00 0.49 (0.33- <0.00 0.66 (0.48- NPV 0.89 (0.4-1) 0.007 0.94 (0.63-1) 0.34 (0.2-0.51) 0.97 (0.81-1) 0.86 (0.6-0.95) 0.04 0.35) 1 0.65) 1 0.81) <0.00 <0.00 <0.00 F1 Score 0.99 0.83 0.88 0.57 0.95 0.63 0.82 0.79 0.002 1 1 1 Itching Cramp Pain NLP (95% ICD (95% CI) P NLP (95% CI) ICD (95% CI) P NLP (95% CI) ICD (95% CI) P CI) 0.98 (0.86- 0.24 (0.09- <0.00 0.09 (0.01- <0.00 0.52 (0.37- <0.00 Sensitivity 0.98 (0.85-1) 0.99 (0.93-1) 1) 0.45) 1 0.29) 1 0.66) 1 0.89 (0.72- 0.5 (0.37- Specificity 0.96 (0.8-1) 0.98 (0.86-1) 0.68 0.98 (0.88-1) 0.18 0.5 (0-1) 1 0.98) 0.66) 0.88 (0.69- PPV 0.96 (0.8-1) 0.8 (0.54-1) 0.32 0.8 (0.16-1) 0.22 0.99 (0.93-1) 0.98 (0.87-1) NA* 0.97) 0.98 (0.85- 0.57 (0.41- <0.00 0.58 (0.43- <0.00 NPV 0.98 (0.86-1) 0.5 (0-1) 0.02 (0-0.08) NA* 1) 0.72) 1 0.72) 1 <0.00 <0.00 <0.00 F1 Score 0.97 0.56 0.91 0.28 0.99 0.68 1 1 1 *Denotes 95% confidence intervals and P values that could not be calculated due to insufficient cells in 2x2 tables.
    [Show full text]
  • Nitrate Prodrugs Able to Release Nitric Oxide in a Controlled and Selective
    Europäisches Patentamt *EP001336602A1* (19) European Patent Office Office européen des brevets (11) EP 1 336 602 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: C07C 205/00, A61K 31/00 20.08.2003 Bulletin 2003/34 (21) Application number: 02425075.5 (22) Date of filing: 13.02.2002 (84) Designated Contracting States: (71) Applicant: Scaramuzzino, Giovanni AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU 20052 Monza (Milano) (IT) MC NL PT SE TR Designated Extension States: (72) Inventor: Scaramuzzino, Giovanni AL LT LV MK RO SI 20052 Monza (Milano) (IT) (54) Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases (57) New pharmaceutical compounds of general effects and for this reason they are useful for the prep- formula (I): F-(X)q where q is an integer from 1 to 5, pref- aration of medicines for prevention and treatment of in- erably 1; -F is chosen among drugs described in the text, flammatory, ischemic, degenerative and proliferative -X is chosen among 4 groups -M, -T, -V and -Y as de- diseases of musculoskeletal, tegumental, respiratory, scribed in the text. gastrointestinal, genito-urinary and central nervous sys- The compounds of general formula (I) are nitrate tems. prodrugs which can release nitric oxide in vivo in a con- trolled and selective way and without hypotensive side EP 1 336 602 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 336 602 A1 Description [0001] The present invention relates to new nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without the side effects typical of nitrate vasodilators drugs.
    [Show full text]
  • Enzyme Mediated Inflammation: Epidemiology and Therapeutic Implications Parteek Prasher*
    Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2016, 8(9):89-100 ISSN : 0975-7384 Review Article CODEN(USA) : JCPRC5 Enzyme Mediated Inflammation: Epidemiology and Therapeutic implications Parteek Prasher* Assistant Professor of Chemistry, University of Petroleum and Energy Study, Energy acres, Uttrakhand, India ___________________________________________________________________________________ ABSTRACT The identification of various enzymes participating in the arachidonic acid metabolism and recognition of inflammatory metabolites led to systematic studies for the development of anti-inflammatory drugs. Starting with the stimulatory role of phospholipases to release arachidonic acid from phospholipids, over-expression of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) enzymes cause more than normal production of the respective metabolites. Excessive production of prostaglandins and leukotrienes leads to the manifestation of acute to chronic inflammation in humans. The consequent ailments are expressed in the form of asthma, atherosclerosis, irritable bowel syndrome, arthritis and cancer. Targeting the induced isoform of cyclooxygenase viz. cyclooxygenase-2 (COX-2) and 5-LOX enzyme has opened new aspects for capping the enzyme mediated inflammation. A number of such aspects have been discussed in this comprehensive review. Keywords: COX; Cyclooxygenase; LOX; Lipoxygenase; Arachidonic acid ___________________________________________________________________________________ INTRODUCTION According to a recent survey of the World Health Organization (WHO), cancer causes around 13% of the total deaths worldwide and if it continues rising, it is estimated to cause 13.1 million deaths in 2030 [1]. Moreover, the reason for about 15% of the total cancer deaths has been reported [2] to be associated with chronic inflammation. Hence, an obvious way out to minimize cancer deaths is to put control over the inflammatory conditions.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
    USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO).
    [Show full text]
  • Toiminta Unita on Ulla La Mungukurti |
    TOIMINTAUNITA USON 20180071390A1ULLA LA MUNGUKURTI | ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2018/ 0071390 A1 PATEL et al. (43 ) Pub . Date : Mar . 15 , 2018 ( 54 ) COMPOSITIONS OF PHARMACEUTICAL A61K 9 / 06 (2006 .01 ) ACTIVES CONTAINING DIETHYLENE A61K 9 /00 (2006 .01 ) GLYCOL MONOETHYL ETHER OR OTHER A61K 31 /573 ( 2006 .01 ) ALKYL DERIVATIVES A61K 31/ 565 ( 2006 .01 ) A61K 31/ 4439 ( 2006 . 01 ) ( 71 ) Applicant : THEMIS MEDICARE LIMITED , A61K 31 / 167 ( 2006 . 01 ) Mumbai (IN ) A61K 31 / 57 (2006 . 01) (52 ) U . S . CI. (72 ) Inventors : Dinesh Shantilal PATEL , Mumbai CPC .. .. .. A61K 47 / 10 ( 2013 . 01 ) ; A61K 9 /4858 ( IN ) ; Sachin Dinesh PATEL , Mumbai ( 2013 .01 ) ; A61K 9 /08 ( 2013 .01 ) ; A61K 9 / 06 ( IN ) ; Shashikant Prabhudas ( 2013 .01 ) ; A61K 9 / 0014 ( 2013 .01 ) ; A61K KURANI, Mumbai ( IN ) ; Madhavlal 31/ 573 ( 2013 .01 ) ; A61K 31 /57 ( 2013 .01 ) ; Govindlal PATEL , Mumbai ( IN ) A61K 31/ 565 ( 2013 .01 ) ; A61K 31 /4439 (73 ) Assignee : THEMIS MEDICARE LIMITED , ( 2013 .01 ) ; A61K 31/ 167 ( 2013 .01 ) ; A61K Mumbai (IN ) 9 /0048 ( 2013 .01 ) ; A61K 9 /0019 (2013 .01 ) ( 57 ) ABSTRACT (21 ) Appl. No .: 15 / 801, 390 The present invention relates to pharmaceutical composi tions of various pharmaceutical actives, especially lyophilic ( 22 ) Filed : Nov . 2 , 2017 and hydrophilic actives containing Diethylene glycol mono ethyl ether or other alkyl derivatives thereof as a primary Related U . S . Application Data vehicle and /or to pharmaceutical compositions utilizing (62 ) Division of application No. 14 /242 , 973 , filed on Apr. Diethylene glycol monoethyl ether or other alkyl derivatives 2 , 2014 , now Pat. No. 9 , 827 ,315 .
    [Show full text]
  • Fatal Hepatitis Associated with Diclofenac
    Gut: first published as 10.1136/gut.27.11.1390 on 1 November 1986. Downloaded from Gut, 1986, 27, 1390-1393 Case reports Fatal hepatitis associated with diclofenac E G BREEN, J McNICHOLL, E COSGROVE, J MCCABE, AND F M STEVENS From the Department of Medicine, Regional Hospital, Galway, Eire SUMMARY Non-steroidal anti-inflammatory agents (NSAIDS) are a well recognised cause of hepatotoxicity. Diclofenac, a relatively new NSAID, was first introduced into the UK in 1979. Five cases of hepatitis have recently been reported, principally in the French literature. -5 We report the first fulminant case of hepatitis in the English literature in a patient taking diclofenac and indomethacin. Diclofenac is a member of the arylalkanoic group of 100 mg per day for five weeks. Ferrous sulphate one NSAIDS (Fig. 1). Three other agents in this group tablet daily was added on 16 May. The patient was have been shown to be significantly hepatotoxic. admitted to hospital on 26 June. A week before this Ibufenac was withdrawn from circulation because of he had felt unwell with anorexia, nausea, abdominal the frequent rise in transaminases,6 7 the use of discomfort, and dark urine. On admission he was benoxaprofen was stopped in Britain after 10 icteric, the liver edge was palpable 4 cm below the patients died with hepatitis8 9 and more recently a costal margin and there were no signs of chronic fatal case of hepatitis due to pirprofen has been liver disease. Ultrasound showed early ascites with reported."' Early reports about diclofenac showed no obstruction of the biliary tract.
    [Show full text]
  • Trabajo De Diploma
    Facultad de Química-Farmacia Departamento de Farmacia Trabajo de diploma Título: Evaluación experimental “in vivo” de nuevos compuestos con actividad analgésica seleccionados a través del tamizaje virtual. Autor: Yulier León Mederos Tutores: Dr. Yovani Marrero Ponce MSc. Arelis López Sacerio 2009-2010 Exergo Todos y cada uno de nosotros paga puntualmente su cuota de sacrificio consciente de recibir el premio en la satisfacción del deber cumplido, conscientes de avanzar con todos hacia el Hombre Nuevo que se vislumbra en el horizonte... Che Yulier León Mederos Evaluación experimental “in vivo” de nuevos compuestos con actividad analgésica seleccionados a través del tamizaje virtual Dedicatoria A alguien que se lo merece, por su ayuda y su apoyo durante esta larga carrera como estudiante universitario, mi madre la cual confió siempre en mí y por ver esperado con paciencia esta gran hazaña. Elisa Jorge por verse convertido en mi madre y por su apoyo incondicional cada día que transcurrió en esta escuela. A mis hermanos por estar siempre a mí lado cuando más yo los necesitaba, a mi abuela que no pudo disfrutar esta gran victoria junto a mí, pero allá donde ella está le llegará este lindo regalo. Yulier León Mederos Evaluación experimental “in vivo” de nuevos compuestos con actividad analgésica seleccionados a través del tamizaje virtual Agradecimientos Esta página está dedicada a todas aquellas personas que de un modo u otro hicieron posible la realización de esta tesis. Quisiera agradecer en primer lugar a mi madre que siempre depositó todo su amor y confianza en mí, sobre todo en los momentos difíciles a lo largo de mi carrera A mis hermanos ya que sus consejos siempre fueron buenos y por el aprecio que siento hacia ellos.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,636.405 B2 Tamarkin Et Al
    USOO9636405B2 (12) United States Patent (10) Patent No.: US 9,636.405 B2 Tamarkin et al. (45) Date of Patent: May 2, 2017 (54) FOAMABLE VEHICLE AND (56) References Cited PHARMACEUTICAL COMPOSITIONS U.S. PATENT DOCUMENTS THEREOF M (71) Applicant: Foamix Pharmaceuticals Ltd., 1,159,250 A 1 1/1915 Moulton Rehovot (IL) 1,666,684 A 4, 1928 Carstens 1924,972 A 8, 1933 Beckert (72) Inventors: Dov Tamarkin, Maccabim (IL); Doron 2,085,733. A T. 1937 Bird Friedman, Karmei Yosef (IL); Meir 33 A 1683 Sk Eini, Ness Ziona (IL); Alex Besonov, 2,586.287- 4 A 2/1952 AppersonO Rehovot (IL) 2,617,754. A 1 1/1952 Neely 2,767,712 A 10, 1956 Waterman (73) Assignee: EMY PHARMACEUTICALs 2.968,628 A 1/1961 Reed ... Rehovot (IL) 3,004,894. A 10/1961 Johnson et al. (*) Notice: Subject to any disclaimer, the term of this 3,062,715. A 1 1/1962 Reese et al. tent is extended or adiusted under 35 3,067,784. A 12/1962 Gorman pa 3,092.255. A 6/1963 Hohman U.S.C. 154(b) by 37 days. 3,092,555 A 6/1963 Horn 3,141,821 A 7, 1964 Compeau (21) Appl. No.: 13/793,893 3,142,420 A 7/1964 Gawthrop (22) Filed: Mar. 11, 2013 3,144,386 A 8/1964 Brightenback O O 3,149,543 A 9/1964 Naab (65) Prior Publication Data 3,154,075 A 10, 1964 Weckesser US 2013/0189193 A1 Jul 25, 2013 3,178,352.
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]
  • Cross-Reactive Mechanism for the False Elevation of Free Triiodothyronine in the Patients Treated with Diclofenac
    Endocrine Journal 2001, 48 (6), 717-722 NOTE Cross-Reactive Mechanism for the False Elevation of Free Triiodothyronine in the Patients Treated with Diclofenac KEIZO KASONO, HAJIME HIKINO*, SHINJI FUJINO**, NoBUYUKI TAKEMOTO*, TosHIHIRO KAI*, KIYosHI YAMAGUCHI***, FUMio KONISHI* AND MASANOBU KAWAKAMI Department of Endocrinology and Metabolism, Jichi Medical School, Omiya Medical Center, 1-847, Amanuma-cho, Saitama 330-8503, Japan *Department of Surgery , Jichi Medical School, Omiya Medical Center, 1-847, Amanuma-cho, Saitama 330-8503, Japan **Department of Pathology , Jichi Medical School, Omiya Medical Center, 1-847, Amanuma-cho, Saitama 330-8503, Japan ***Department of Neurology , Jichi Medical School, Omiya Medical Center, 1-847, Amanuma-cho, Saitama 330-8503, Japan Abstract. We report three cases of patients exhibiting a false elevation of serum free triiodothyronine (FT3) as a result of a cross-reaction with diclofenac. The first case is a 66-yr-old woman with a long history of rheumatoid arthritis (RA). The patient was receiving diclofenac for the treatment of her RA. The patient was subsequently diagnosed as having thyroid papillary adenocarcinoma and received a subtotal thyroidectomy. After the operation, the patient exhibited postoperative hypothyroidism except for a gradual elevation of FT3. The other two patients also exhibited an elevated serum FT3 level after the administration of diclofenac. Serum FT3 levels in these pa- tients decreased to normal or below normal after diclofenac administration was discontinued. In the first case, the elimination of immunoglobulin from the sera using polyethylene glycol precipitation did not reduce the FT3 level. In our hospital, Vitros ECi (enhanced chemiluminescence enzyme immunoassay) system and Vitros FT3 kit were used for FT3 assay.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,795,310 B2 Lee Et Al
    US00779531 OB2 (12) United States Patent (10) Patent No.: US 7,795,310 B2 Lee et al. (45) Date of Patent: Sep. 14, 2010 (54) METHODS AND REAGENTS FOR THE WO WO 2005/025673 3, 2005 TREATMENT OF METABOLIC DISORDERS OTHER PUBLICATIONS (75) Inventors: Margaret S. Lee, Middleton, MA (US); Tenenbaum et al., “Peroxisome Proliferator-Activated Receptor Grant R. Zimmermann, Somerville, Ligand Bezafibrate for Prevention of Type 2 Diabetes Mellitus in MA (US); Alyce L. Finelli, Patients With Coronary Artery Disease'. Circulation, 2004, pp. 2197 Framingham, MA (US); Daniel Grau, 22O2.* Shen et al., “Effect of gemfibrozil treatment in sulfonylurea-treated Cambridge, MA (US); Curtis Keith, patients with noninsulin-dependent diabetes mellitus'. The Journal Boston, MA (US); M. James Nichols, of Clinical Endocrinology & Metabolism, vol. 73, pp. 503-510, Boston, MA (US) 1991 (see enclosed abstract).* International Search Report from PCT/US2005/023030, mailed Dec. (73) Assignee: CombinatoRx, Inc., Cambridge, MA 1, 2005. (US) Lin et al., “Effect of Experimental Diabetes on Elimination Kinetics of Diflunisal in Rats.” Drug Metab. Dispos. 17:147-152 (1989). (*) Notice: Subject to any disclaimer, the term of this Abstract only. patent is extended or adjusted under 35 Neogi et al., “Synthesis and Structure-Activity Relationship Studies U.S.C. 154(b) by 0 days. of Cinnamic Acid-Based Novel Thiazolidinedione Antihyperglycemic Agents.” Bioorg. Med. Chem. 11:4059-4067 (21) Appl. No.: 11/171,566 (2003). Vessby et al., “Effects of Bezafibrate on the Serum Lipoprotein Lipid and Apollipoprotein Composition, Lipoprotein Triglyceride Removal (22) Filed: Jun. 30, 2005 Capacity and the Fatty Acid Composition of the Plasma Lipid Esters.” Atherosclerosis 37:257-269 (1980).
    [Show full text]