DOCSLIB.ORG

( 12 ) United States Patent

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
( 12 ) United States Patent US010512655B1 (12 ) United States Patent ( 10 ) Patent No.: US 10,512,655 B1 Brooks (45 ) Date of Patent : Dec. 24 , 2019 ( 54 ) METHODS AND COMPOSITIONS FOR THE Ghosh et al. , “ Methods of Enhancement of Transdermal Drug TOPICAL TREATMENT OF PERIPHERAL Delivery : Part IIB , Chemical Permeation Enhancers ” , Pharmaceu NEUROPATHY tical Technology, 17 ( 5 ) , 68-76 , May 1993 . Swinyard et al ., " Pharmaceutical Necessities ” , Remington's Phar ( 71) Applicant: Jeffrey S. Brooks, Inc., St. Louis , MO maceutical Sciences , 1985, 17th Edition , Chapter 68 , pp . 1278 1320 . (US ) Head , K. , “ Peripheral Neuropathy : Pathogenic Mechanisms and (72 ) Inventor: Jeffrey S. Brooks, St. Louis , MO (US ) Alternative Therapies ” , Alternative Medicine Review , 2006 , 11 ( 4 ) : 294-329 . ( 73 ) Assignee: Jeffrey S. Brooks, Inc., St. Louis , MO Balakumar , P. et al. , “ The multifaceted therapeutic potential of (US ) benfotiamine ” , Pharmacological Research , 2010 , 61 : 482-488 . Fraser , D.A. et al. , “ The effects of long - term oral benfotiamine ( * ) Notice : Subject to any disclaimer , the term of this supplementation on peripheral nerve function and inflammatory patent is extended or adjusted under 35 markers in patients with type 1 diabetes : a 24 -month , double- blind , randomized , placebo -controlled trial ” , Diabetes Care , 2012 , 35 ( 5 ) : 1095 U.S.C. 154 ( b ) by 296 days . 1097 . Fonseca et al. , “ Metanx in Type 2 Diabetes with Peripheral Neuropathy: ( 21) Appl. No .: 14 /202,161 A Randomized Trial” , A Med J , 2013 , 126 ( 2 ) : 141-149 . Filed : Bighley et al ., “ Salt Forms of Drugs and Absorption, ” in Encyclo ( 22 ) Mar. 10 , 2014 pedia of Pharmaceutical Technology , J. Swarbrick and J.C. Boylan , Eds. (Marcel Dekker , New York , 1996 ) , vol. 13 , pp . 453-499 . Related U.S. Application Data Hahn , John , “ The Naturopathic Management of Diabetic Peripheral (60 ) Provisional application No. 61/ 777,582 , filed on Mar. Neuropathy” , Townsend Letter, 2010 , Feb.- March , pp . 56-62 . Parminder et al. , " Current Therapeutic Strategies in Diabetic 12 , 2013 . Neuropathy ” , International Research Journal of Pharmacy , 2012 , 3 ( 3 ): 22-29 . (51 ) Int. Ci. Boulton et al. , “ Diabetic Peripheral Neuropathy : Diagnosis and A61K 31/675 ( 2006.01 ) Management” , Medscape Education, pp . 1-49, released Aug. 16 , A61K 45/06 ( 2006.01 ) 2011 . A61K 31/485 ( 2006.01 ) St. Onge et al. , “ Pain Associated with Diabetic Peripheral Neuropathy ” , A61K 31/519 ( 2006.01) P & T , Mar. 2008 , 33 ( 3 ) : 166-176 . ( 52 ) U.S. CI. Ang et al ., “ Vitamin B for treating peripheral neuropathy ( Review ) ” , CPC Cochrane Database System Review , 2008 , 16 ( 3 ) : 1-39 . A61K 31/675 ( 2013.01 ) ; A61K 31/485 Cheng et al. , “ Painful Diabetic Neuropathy ” , Neuropathic Pain : ( 2013.01) ; A61K 31/519 (2013.01 ) ; A61K Mechanisms, Diagnosis and Treatment, Chapter 11 , 2012 , pp . 45/06 (2013.01 ) 165-189 . (58 ) Field of Classification Search “ Topical Drugs” , Remington : The Science and Practice of Phar CPC A61K 31/675 ; A61K 31/51 macy , 20th edition , (Lippincott , Williams & Wilkins, 2003 ) , Chapter See application file for complete search history . 65, pp . 1200-1218 . Authia Cream , Commercial product description [online ], Westlake ( 56 ) References Cited Laboratories Inc. ( retrieved on Aug. 15 , 2014 ] . Retrieved from the Internet : < URL : www.westlake-labs.com/products/authia-cream > . U.S. PATENT DOCUMENTS Neuro- Immune Stabilizer Topical Cream , Commercial product descrip tion [online ], Neuro Biologix [ retrieved on Aug. 15 , 2014 ]. Retrieved 6,143,278 A 11/2000 Elkhoury from the Internet : < URL : www.neurobiologix.com/Neuro-Immune 7,235,249 B2 6/2007 Bissett 7,666,442 B2 2/2010 Morariu Stabilizer - B12-136 - Vitamin - D - Cream - p /46.htm > . 8,137,711 B2 3/2012 Wolicki Topical B Complex , Commercial product description [ online ], 2005/0019354 A1 1/2005 Perricone Sarati Labs (retrieved on Aug. 15 , 2014 ] , Retrieved from the 2006/0045896 A1 * 3/2006 Morariu A61K 8/4926 Internet : <URL : www.amazon.com/Topical-Complex-Sarati-Labs 424/401 Tube / dp /B00ONGM342 > . 2006/0084066 A1 4/2006 Sah et al . (Continued ) 2007/0190126 A1 * 8/2007 Stuart A61K 9/0014 424/449 Primary Examiner Rachael E Bredefeld 2008/0102137 Al 5/2008 Guffey 2009/0311167 A1 12/2009 Height et al. (74 ) Attorney, Agent, or Firm Stinson LLP 2010/02 10582 A1 8/2010 Stewart et al. 2010/0279984 Al 11/2010 Bonke et al. (57 ) ABSTRACT 2011/0263710 Al 10/2011 Moskowitz et al . Methods for the treatment of peripheral neuropathy are provided which include applying a topical composition to a OTHER PUBLICATIONS peripheral appendage of a subject in need of such treatment. Smith et al. , Percutaneous Penetration Enhancers , Chapter 1.1 and The topical composition includes a B1 vitamer , a B6 vita Chapter 1.2 , 1995 , pp . 1-20 . mer , and a B9 vitamer in a dermatologically acceptable Ghosh et al. , “ Methods of Enhancement of Transdermal Drug carrier . The methods are effective in preventing further Delivery : Part I, Physical and Biochemical approaches ” , Pharma degeneration and / or restoring epidermal nerve fiber density ceutical Technology , 17 ( 3 ) , 72-98 , Mar. 1993 . (ENFD ) in patients with peripheral neuropathy, and in Ghosh et al ., “ Methods of Enhancement of Transdermal Drug preventing or alleviating neuropathic pain . Delivery: Part IIA , Chemical Permeation Enhancers” , Pharmaceu tical Technology , 17 ( 4 ) , 62-90 , Apr. 1993 . 29 Claims, No Drawings US 10,512,655 B1 Page 2 ( 56 ) References Cited OTHER PUBLICATIONS Jayabalan , B., et al. , “ Vitamin B Supplementation for Diabetic Peripheral Neuropathy, ” Singapore Medical Journal, 2016 , pp . 55-59 , vol. 57 , No. 2 . * cited by examiner US 10,512,655 B1 1 2 METHODS AND COMPOSITIONS FOR THE because of issues associated with tolerance and addiction . TOPICAL TREATMENT OF PERIPHERAL Drug therapy for symptomatic relief in DPN includes the use NEUROPATHY of tricyclic antidepressants , serotonin and norepinephrine reuptake inhibitors, N -methyl - D -aspartate (NMDA ) antago CROSS - REFERENCE TO RELATED 5 nists , anticonvulsants , and opioids. Unfortunately , there is no evidence that any of these agents modifies the underlying APPLICATIONS pathophysiology of DPN . This application claims the benefit of U.S. Provisional To date , three oral medications have been approved by the Patent Application Ser. No. 61 / 777,582 , filed Mar. 12 , 2013 , U.S. Food and Drug Administration (FDA ) for treatment of the entirety of which is herein incorporated by reference . 10 DPN pain . Pregabalin (Lyrica , commercially available from Pfizer, New York , N.Y.) is an anticonvulsant agent that FIELD OF THE INVENTION binds with high affinity to the a2-8 subunit of calcium channels . This is thought to produce an analgesic effect by The present invention relates to methods and composi decreasing Ca + 2 influx into nerve terminals and decreases tions for the topical treatment of peripheral neuropathy. 15 neurotransmitter release . Side effects of pregabalin include More particularly , the present invention relates to methods dizziness , somnolence , dry mouth , edema, blurred vision , and topical compositions to decrease neuropathic pain and weight gain , and attention deficit . A further side effect increase epidermal nerve fiber density . associated with Lyrica® is an increased risk of suicidal thoughts and behavior. BACKGROUND OF THE INVENTION 20 Duloxetine (Cymbalta® , commercially available from Eli Lilly , Indianapolis , Ind . ) is an antidepressant that inhibits Peripheral neuropathy , characterized by slow nerve con serotonin and norepinephrine reuptake. Its mechanism of duction and by pain , numbness , and tingling in the extremi action involves an increased availability of 5 -hy ties , can be extremely debilitating . Pain is a serious symp droxytryptamine and noradrenaline, which suppress pain tom formany patients , and may be described as a dull aching 25 impulses . Side effects of duloxetine include headache, sensation , an intense burning sensation , or as intermittent, fatigue, nauseas , constipation , and increased blood pressure . stabbing pain . On occasion , patients notice that their skin is This drug cannot be used to treat patients with liver disease, hypersensitive to tactile sensation , such as from standing on renal failure , or glaucoma. their feet or from the touch of clothing or bedding . Some Tramadol (Nucynta® , commercially available from John patients note an exaggerated pain resulting from stimulus to 30 son & Johnson , New Brunswick , N.J.) is a u - opioid agonist the affected area , a form of pain termed allodynia . that also inhibits reuptake of serotonin . Adverse effects Peripheral neuropathy encompasses a wide spectrum of include respiratory depression , nausea , somnolence , vomit clinical disorders that affect sensory , motor , and autonomic ing, and headache. Patients receiving tramadol require care peripheral nerve fibers. Nerve fiber dysfunction can be the ful monitoring for signs of abuse and addiction . Risk for result of genetics , systemic or infectious disease, environ- 35 addiction occurs even under appropriate medical use , and is mental toxins , alcoholism , nutritional deficiencies , or the increased for patients with a family history of substance side effect of certain medications. Peripheral neuropathy can abuse ( including alcohol or drugs ) or mental illness ( e.g. also be caused by traumatic injury, surgery , radiation , and major depression ). chemotherapy
Load more

Recommended publications
  • Transition from Acute to Chronic Postsurgical Pain: Risk Factors and Protective Factors
    Review For reprint orders, please contact [email protected] Transition from acute to chronic postsurgical pain: risk factors and protective factors Expert Rev. Neurother. 9(5), 723–744 (2009) Joel Katz† and Most patients who undergo surgery recover uneventfully and resume their normal daily Ze’ev Seltzer activities within weeks. Nevertheless, chronic postsurgical pain develops in an alarming †Author for correspondence proportion of patients. The prevailing approach of focusing on established chronic pain Department of Psychology, implicitly assumes that information generated during the acute injury phase is not important BSB 232, York University, to the subsequent development of chronic pain. However, a rarely appreciated fact is that 4700 Keele Street, Toronto, every chronic pain was once acute. Here, we argue that a focus on the transition from acute ON M3J 1P3, Canada to chronic pain may reveal important cues that will help us to predict who will go on to develop Tel.: +1 416 736 2100 chronic pain and who will not. Unlike other injuries, surgery presents a unique set of ext. 40557 circumstances in which the precise timing of the physical insult and ensuing pain are known Fax: +1 416 736 5814 in advance. This provides an opportunity, before surgery, to identify the risk factors and [email protected] protective factors that predict the course of recovery. In this paper, the epidemiology of chronic postsurgical pain is reviewed. The surgical, psychosocial, socio–environmental and patient- related factors that appear to confer a greater risk of developing chronic postsurgical pain are described. The genetics of chronic postsurgical pain are discussed with emphasis on known polymorphisms in human genes associated with chronic pain, genetic studies of rodent models of pain involving surgical approaches, the importance of developing accurate human chronic postsurgical pain phenotypes and the expected gains for chronic postsurgical pain medicine For personal use only.
    [Show full text]
  • Curriculum Vitae
    Curriculum Vitae PERSONAL INFORMATION Martin Bauer WORK EXPERIENCE December 2004-January 2005 Research associate Medical University of Vienna, Department of Clinical Pharmacology (Austria) Phase I and II studies Pharmacokinetics PET/MR Imaging studies Assessing target tissue penetration with Positron Emission Tomography and Microdialysis DDIs July 2017- Present Senior Consultant Medical University of Vienna, Department of Psychiatry and Psychotherapy (Austria) Outpatients clinic, psychiatric intermediate care unit, emergency psychiatry, memory clinic, Phase II-IV studies March 2011- Present Registered Consultant in Clinical Pharmacology Medical University of Vienna/Vienna General Hospital (Austria) Clinacal pharmacology outpatient clinics, DDIs, pharmacokinetics, microdialysis, PET/MR imaging of ABC transporters, Phase I-II studies March 2014- Present Registered Consultant in Psychiatry Medical University of Vienna/Vienna General Hospital (Austria) General psychiatry, Schizophrenia, affective disorders, dementia, child and adolescent psychiatry March 2015- Present Ethics committee member Medical University of Vienna/Vienna General Hospital (Austria) Reviewing projects, discussion July 2016- Present Associate Professor of Clinical Pharmacology Medical University of Vienna/Vienna General Hospital (Austria) Teaching, provide training, Senior Principal Investigator Clinical Research Phase I-II studies, DDIs, pharmacokinetics, bioequivalence, microdialysis, PET/MR imaging of ABC transporters EDUCATION AND TRAINING January 2005-March 2014 Clinical
    [Show full text]
  • Drug Delivery System for Use in the Treatment Or Diagnosis of Neurological Disorders
    (19) TZZ __T (11) EP 2 774 991 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 10.09.2014 Bulletin 2014/37 C12N 15/86 (2006.01) A61K 48/00 (2006.01) (21) Application number: 13001491.3 (22) Date of filing: 22.03.2013 (84) Designated Contracting States: • Manninga, Heiko AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 37073 Göttingen (DE) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO •Götzke,Armin PL PT RO RS SE SI SK SM TR 97070 Würzburg (DE) Designated Extension States: • Glassmann, Alexander BA ME 50999 Köln (DE) (30) Priority: 06.03.2013 PCT/EP2013/000656 (74) Representative: von Renesse, Dorothea et al König-Szynka-Tilmann-von Renesse (71) Applicant: Life Science Inkubator Betriebs GmbH Patentanwälte Partnerschaft mbB & Co. KG Postfach 11 09 46 53175 Bonn (DE) 40509 Düsseldorf (DE) (72) Inventors: • Demina, Victoria 53175 Bonn (DE) (54) Drug delivery system for use in the treatment or diagnosis of neurological disorders (57) The invention relates to VLP derived from poly- ment or diagnosis of a neurological disease, in particular oma virus loaded with a drug (cargo) as a drug delivery multiple sclerosis, Parkinsons’s disease or Alzheimer’s system for transporting said drug into the CNS for treat- disease. EP 2 774 991 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 774 991 A1 Description FIELD OF THE INVENTION 5 [0001] The invention relates to the use of virus like particles (VLP) of the type of human polyoma virus for use as drug delivery system for the treatment or diagnosis of neurological disorders.
    [Show full text]
  • Orally Active Compound Library (96-Well)
    • Bioactive Molecules • Building Blocks • Intermediates www.ChemScene.com Orally Active Compound Library (96-well) Product Details: Catalog Number: CS-L061 Formulation: A collection of 2244 orally active compounds supplied as pre-dissolved Solutions or Solid Container: 96- or 384-well Plate with Peelable Foil Seal; 96-well Format Sample Storage Tube With Screw Cap and Optional 2D Barcode Storage: -80°C Shipping: Blue ice Packaging: Inert gas Plate layout: CS-L061-1 1 2 3 4 5 6 7 8 9 10 11 12 a Empty Vonoprazan Mivebresib AZD0156 BAY-876 Tomivosertib PQR620 NPS-2143 R547 PAP-1 Delpazolid Empty Varenicline b Empty Varenicline (Hydrochlorid Varenicline A-205804 CI-1044 KW-8232 GSK583 Quiflapon MRK-016 Diroximel Empty e) (Tartrate) fumarate SHP099 c Empty A 922500 SHP099 (hydrochlorid Nevanimibe Pactimibe Pactimibe GNF-6231 MLi-2 KDM5-IN-1 PACMA 31 Empty e) hydrochloride (sulfate) Rilmenidine d Empty Cadazolid Treprostinil GSK3179106 Esaxerenone (hemifumarat Rilmenidine Fisogatinib BP-1-102 Avadomide Aprepitant Empty e) (phosphate) Cl-amidine AZD5153 (6- e Empty Maropitant Abscisic acid (hydrochlorid BGG463 WNK463 Ticagrelor Axitinib Hydroxy-2- CGS 15943 Pipamperone Empty e) naphthoic Setogepram Teglarinad f Empty Y-27632 GSK2193874 Lanabecestat CXD101 Ritlecitinib YL0919 PCC0208009 (sodium salt) (chloride) Futibatinib Empty TAK-659 g Empty NCB-0846 GS-444217 (hydrochlorid Navitoclax ABX464 Zibotentan Simurosertib (R)- CEP-40783 MK-8617 Empty e) Simurosertib Choline JNJ- h Empty CCT251236 (bitartrate) Sarcosine Brensocatib AS-605240 PF-06840003
    [Show full text]
  • Mitigating the Inhibition of Human Bile Salt Export Pump by Drugs
    DMD Fast Forward. Published on September 7, 2012 as DOI: 10.1124/dmd.112.047068 DMD FastThis Forward. article has not Published been copyedited on andSeptember formatted. The 7, final 2012 version as doi:10.1124/dmd.112.047068may differ from this version. DMD #47968 Mitigating the inhibition of human Bile Salt Export Pump by drugs: opportunities provided by physicochemical property modulation, in-silico modeling and structural modification Daniel J. Warner, Hongming Chen, Louis-David Cantin, J. Gerry Kenna, Simone Stahl, Clare L. Walker, Tobias Noeske. Department of Medicinal Chemistry, AstraZeneca R&D Montreal, Montreal, Quebec, H4S Downloaded from 1Z9, Canada (DJW, LDC) Computational Sciences, Discovery Sciences, AstraZeneca R&D Mölndal, Pepparedsleden dmd.aspetjournals.org 1, Mölndal 43183, Sweden (HC) Molecular Toxicology, Global Safety Assessment, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK (JGK, SS, CLW) Global Safety Assessment, AstraZeneca R&D Mölndal, Pepparedsleden 1, Mölndal 43183, at ASPET Journals on October 10, 2021 Sweden (TN) 1 Copyright 2012 by the American Society for Pharmacology and Experimental Therapeutics. DMD Fast Forward. Published on September 7, 2012 as DOI: 10.1124/dmd.112.047068 This article has not been copyedited and formatted. The final version may differ from this version. DMD #47968 Inhibition of the human Bile Salt Export Pump by drugs. Corresponding author: Tobias Noeske Global Safety Assessment AstraZeneca R&D Mölndal S-431 83 Mölndal, Sweden Phone: +46-31-7064002 Mobile: +46-727-158344
    [Show full text]
  • Effects of Ralfinamide in Models of Nerve Injury and Chemotherapy-Induced Neuropathic Pain
    European Journal of Pharmacology 823 (2018) 27–34 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar Full length article Effects of ralfinamide in models of nerve injury and chemotherapy-induced T neuropathic pain ⁎ ⁎ Xiaonan Liang, Gang Yu , Ruibin Su State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China ARTICLE INFO ABSTRACT Keywords: Neuropathic pain is among the most common and difficult-to-treat types of chronic pain and is associated with Neuropathic pain sodium channel malfunction. The sodium channel blocker ralfinamide has exhibited potent analgesic effects in Sodium channel blocker several preclinical pain models and in patients with mixed neuropathic pain syndromes (Phase II trials), but it fi Ral namide failed to ameliorate neuropathic low back pain in Phase III trials. It is unclear whether ralfinamide is effective Analgesic against neuropathic pain induced by specified etiologies. In the present study, the antinociceptive effects of ralfinamide in neuropathic pain models induced by spared nerve injury and chemotherapy were compared in a gabapentin-controlled manner. The effects of ralfinamide on physiological pain were evaluated in mechanical withdrawal, hot plate, and acetic acid writhing tests. We also investigated the effects of ralfinamide on cardi- ovascular function and locomotor activity. Oral ralfinamide dose-dependently alleviated spared nerve injury- induced allodynia in rats and mice. Ralfinamide increased mechanical withdrawal thresholds in oxaliplatin- induced and paclitaxel-induced neuropathic pain. Ralfinamide did not affect physiological pain, locomotion, or cardiovascular function. Together, ralfinamide attenuated mechanical allodynia in all the neuropathic pain models tested, with subtle differences in efficacy.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,076,515 B2 Barbanti Et Al
    USO08076515B2 (12) United States Patent (10) Patent No.: US 8,076,515 B2 Barbanti et al. (45) Date of Patent: Dec. 13, 2011 (54) PROCESS FOR THE PRODUCTION OF 2007/0093495 A1 4/2007 Ruggero et al. 2007/0203182 A1 8, 2007 Besana et al. 2-4-(3- AND 2-FLUOROBENZYLOXY) 2007/0276046 A1 11/2007 Salvati et al. BENZYLAMINO PROPANAMIDES 2008, 0096965 A1 4/2008 Barbanti et al. 2008/O132567 A1 6/2008 Barbanti et al. (75) Inventors: Elena Barbanti, Cologno Monzese (IT): 2010, OO16437 A1 1/2010 Salvati et al. Carla Caccia, Cardano Al Campo (IT): 2010/0324141 A1 12/2010 Barbanti et al. Patricia Salvati, Arese (IT): Francesco 2011/0014304 A1 1/2011 IZZO et al. Velardi, Cameri (IT): Tiziano Ruffili, FOREIGN PATENT DOCUMENTS Vigliano Biellese (IT): Luigi Bogogna, EP 04.00495 A1 12, 1990 Vaprio D'Agogna (IT) EP 1655O29 A 5, 2006 WO WO 2004/066987 A2 8, 2004 (73) Assignee: Newron Pharmaceuticals S.p.A., WO WO 2005/040138 A1 5, 2005 Bresso (IT) WO WO 2005,102300 A1 11/2005 WO WO 2006/027052 A2 3, 2006 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 OTHER PUBLICATIONS U.S.C. 154(b) by 551 days. Stummann et al., 2005. “The anti-nociceptive agent ralfinamide inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ cur (21) Appl. No.: 12/338,825 rents in dorsal root ganglion neurons.” European Journal of Phar macology, 510: 197-208. (22) Filed: Dec. 18, 2008 Cattabeni, 2004, “Ralfinamide.” Idrugs, Current Drugs Ltd., pp.
    [Show full text]
  • Sodium Channel Na Channels; Na+ Channels
    Sodium Channel Na channels; Na+ channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change (Voltage-gated, voltage-sensitive, or voltage-dependent sodium channel also called VGSCs or Nav channel) or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. Voltage-gated Na+ channels can exist in any of three distinct states: deactivated (closed), activated (open), or inactivated (closed). Ligand-gated sodium channels are activated by binding of a ligand instead of a change in membrane potential. www.MedChemExpress.com 1 Sodium Channel Inhibitors, Agonists, Antagonists, Activators & Modulators (+)-Kavain (-)-Sparteine sulfate pentahydrate Cat. No.: HY-B1671 ((-)-Lupinidine sulfate pentahydrate) Cat. No.: HY-B1304 (+)-Kavain, a main kavalactone extracted from Piper (-)-Sparteine sulfate pentahydrate ((-)-Lupinidine methysticum, has anticonvulsive properties, sulfate pentahydrate) is a class 1a antiarrhythmic attenuating vascular smooth muscle contraction agent and a sodium channel blocker. It is an through interactions with voltage-dependent Na+ alkaloid, can chelate the bivalents calcium and and Ca2+ channels. magnesium. Purity: 99.98% Purity: ≥98.0% Clinical Data: Launched Clinical Data: Launched Size: 10 mM × 1 mL, 5 mg, 10 mg Size: 10 mM × 1 mL, 50 mg (Rac)-AMG8379 20(S)-Ginsenoside Rg3 ((Rac)-AMG8380) Cat. No.: HY-108425B (20(S)-Propanaxadiol; S-ginsenoside Rg3) Cat.
    [Show full text]
  • Preventive Analgesia: Quo Vadimus?
    REVIEW ARTICLE Preventive Analgesia: Quo Vadimus? Joel Katz, PhD,*§¶ Hance Clarke, MSc, MD,§¶ and Ze’ev Seltzer, BMS, DMD§# The classic definition of preemptive analgesia requires 2 groups of patients to receive identical treatment before or after incision or surgery. The only difference between the 2 groups is the timing of administration of the drug relative to incision. The constraint to include a postincision or postsurgical treatment group is methodologically appealing, because in the presence of a positive result, it provides a window of time within which the observed effect occurred, and thus points to possible mechanisms underlying the effect: the classic view assumes that the intraoperative nociceptive barrage contributes to a greater extent to postoperative pain than does the postoperative nociceptive barrage. However, this view is too restrictive and narrow, in part because we know that sensitization is induced by factors other than the peripheral nociceptive barrage associated with incision and subsequent noxious intraoperative events. A broader approach to the prevention of postoperative pain has evolved that aims to minimize the deleterious immediate and long-term effects of noxious perioper- ative afferent input. The focus of preventive analgesia is not on the relative timing of analgesic or anesthetic interventions, but on attenuating the impact of the peripheral nociceptive barrage associated with noxious preoperative, intraoperative, and/or postoperative stimuli. These stimuli induce peripheral and central sensitization, which increase postoperative pain intensity and analgesic requirements. Preventing sensitization will reduce pain and analgesic requirements. Preventive analgesia is demonstrated when postoperative pain and/or analge- sic use are reduced beyond the duration of action of the target drug, which we have defined as 5.5 half-lives of the target drug.
    [Show full text]
  • (DTX) 217 – Selectivity 219 A-278637
    467 Index a – pentylenetetrazol 357 ff. a interaction domain 71 – picrotoxin 357 a1 subunit 69 ff. antiepileptic drugs, receptor sites 9 a2-d subunit 57, 69 ff. antiepileptics 87 a-Dendrotoxin (DTX) 217 anxiety 369 – selectivity 219 – canopy test 369 ff. A-278637 344 ff. apamin 242, 244, 326 f. A- 411873 323 apoptosis 237 acetylcholine receptor deficiency 408 –Fas receptor 237 AChR 410 – mitochondria 237 action potential 44, 55 aryloxindole 321 adipocytes 244 ff. arylpyrrole 323 – brown fat 244 asthma 324 – glucose transporter 244 ATP-sensitive potassium channel KATP 335, – white fat 244 385 afterhyperpolarization 314 atrial effective refractory period (AERP) Agenelopsis aperta 131 291 alkaloid 319, 328 atrial fibrillation 276 ALMOND modul 432 ff. atrial vulnerability 291 Alzheimer’s disease 317 autism 396 ambasilide 278 autoantibodies 238 amiloride-sensitive epithelial sodium autoimmune diseases 247 ff. channel 397 autosomal dominant 4-aminopyridine 222 – juvenile myoclonic epilepsy 412 amiodarone 29, 278 – nocturnal frontal lobe epilepsy 410 amitriptyline, NaV blocking activity 186 auxiliary subunit in amlodipine 89 ff. –Kvb 11 amygdala-kindling model 357 ff., 361 – KChIp1-4 11 anandamide 91 – minK 11 ancillary calcium channel subunits 69 ff., auxiliary subunits 77 –Cava210 Andersen-Tawil syndrome 383 –Cavb 10 anesthetics 87 –Cavd 10 anosmia 251 –Cavg 10 antiarrhythmic drugs 9, 278 –Navb19 anticonvulsant –ofK+ channels 198 – amygdala-kindling 357 ff. AVE0118 287, 289 –6Hz model 361 azaindole 323 – maximal electroshock 357 ff. azimilide 278 Voltage-Gated Ion Channels as Drug Targets. Edited by D. Triggle Copyright c 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-31258-7 468 Index b – dialkyl-dipeptidylamines 132 b cell rest 341 – dihydropyridines 139 ff.
    [Show full text]
  • | Hao Watum Ut Til a T Man at Malat
    |HAO WATUM UT US010087143B2TIL A T MAN AT MALAT (12 ) United States Patent (10 ) Patent No. : US 10 , 087 , 143 B2 Hadida - Ruah et al. (45 ) Date of Patent: * Oct. 2 , 2018 ( 54 ) PYRIDONE AMIDES AS MODULATORS OF 8 , 779 , 197 B2 7 / 2014 Chen 8 , 841, 483 B2 9 /2014 Joshi SODIUM CHANNELS 8 , 865, 771 B2 10 / 2014 Chen 9 ,051 , 270 B2 * 6 /2015 Hadida - Ruah .. .. C07D 213 / 75 ( 71 ) Applicant: VERTEX PHARMACEUTICALS 9 , 108 ,903 B28 /2015 Hadida - Ruah INCORPORATED , Boston , MA (US ) 9 , 139 ,529 B2 9 /2015 Hadida - Ruah 9 , 163 ,042 B2 10 /2015 Anderson (72 ) Inventors : Sara Sabina Hadida - Ruah , La Jolla , 9 , 393 ,235 B2 * 7 / 2016 Hadida -Ruah .. .. .. CO7D 213 / 75 CA (US ) ; Corey Anderson , San Diego , 9 ,421 , 196 B2 8 /2016 Hadida - Ruah CA (US ) ; Vijayalaksmi Arumugam , 9 , 464 , 102 B2 10 / 2016 Anderson San Marco , CA (US ) ; Iuliana Luci (Continued ) Asgian , San Diego , CA ( US ) ; Brian Richard Bear , Carlsbad , CA (US ) ; FOREIGN PATENT DOCUMENTS Andreas P . Termin , Encinitas, CA CN 101883758 11 / 2010 (US ) ; James Philip Johnson , San CN 102264722 11/ 2011 Diego , CA (US ) (Continued ) (73 ) Assignee : VERTEX PHARMACEUTICALS INCORPORATED , Boston , MA (US ) OTHER PUBLICATIONS ( * ) Notice: Subject to any disclaimer, the term of this Akopian , A . N ., L . Sivilotti, and J. N . Wood , “ A tetrodotoxin patent is extended or adjusted under 35 resistant voltage - gated sodium channel expressed by sensory neu U . S . C . 154 (b ) by 0 days . rons .” Nature , 1996 . 379 ( 6562 ) : p . 257 -62 ). This patent is subject to a terminal dis ( Continued ) claimer .
    [Show full text]
  • Product List
    PRODUCT LIST Active Pharma Ingredients API Acid Reflux Disorders Product Pharmacopoeia CAS No. Technical Document A Acotiamide Hydrochloride - 773092-05-0 - Almagate EP 66827-12-1 - Aluminum Hydroxide BP, USP 21645-51-2 - C Cimetidine - 51481-61-9 - D Dexlansoprazole - 138530-94-6 - Dexlansoprazole - 313640-86-7 DMF Sesquihydrate Dexrabeprazole Sodium - 171440-18-9 ODMF, Tech Pack E Ecabet Sodium - 86408-72-2 DMF Esomeprazole - 119141-88-7 - Esomeprazole Magneisum - 217087-10-0 - Dihydrate Esomeprazole Magnesium - 161973-10-0 - Esomeprazole Magnesium USP 217087-09-7 CEP, DMF Trihydrate Esomeprazole Potassium IHS 161796-84-5 DMF Esomeprazole Sodium - 161796-78-7 - Esomeprazole Zinc/ 793668-08-3, - - Base/Strontium 119141-88-7 F Famotidine - 76824-35-6 - E Glycopyrrolate - 596-51-0 - H Hydrotelcite BP 12304-65-3 - I Ilaprazole IHS, IP 172152-36-2 DMF Ilaprazole Sodium - 172152-50-0 ODMF, Tech Pack Itopride - 122898-67-3 - Itopride Hydrochloride IHS 122892-31-3 - Patent Disclaimer: Products protected by valid patents are not offered for sale in countries, where the sale of such products constitutes a patent infringement. The buyers should make their independent evaluation of the patent scenario for their respective markets and will be responsible for all patent related liabilities. 2021-01-11 © ExSyn Corp | All rights reserved. | www.exsyncorp.com 1 API Acid Reflux Disorders Product Pharmacopoeia CAS No. Technical Document L Lafutidine - 118288-08-7 - Lansoprazole - 103577-45-3 - Lansoprazole Sodium - 226904-00-3 - M Magaldrate USP 74978-16-8
    [Show full text]