DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,969,397 B2 Burright Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,969,397 B2 Burright Et Al US008969397B2 (12) United States Patent (10) Patent No.: US 8,969,397 B2 Burright et al. (45) Date of Patent: *Mar. 3, 2015 (54) SYSTEMS AND METHODS TO TREAT PAIN (58) Field of Classification Search LOCALLY CPC A61 K31/40; A61K 31/405; A61 K31/4168; A61K 31/44; A61K 31/47; A61 K47/48369; (75) Inventors: Eric N. Burright, Eagan, MN (US); A61 K9/1647 Lisa L. Shafer, Stillwater, MN (US); USPC .......... 424/424, 489: 514/275, 277, 311, 419, Bill McKay, Memphis, TN (US); John 514/423, 460, 529, 385 Zanella, Cordova, TN (US) See application file for complete search history. (73) Assignee: Warsaw Orthopedic, Inc., Warsaw, IN (56) References Cited (US) U.S. PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this 4,692,147 A 9/1987 Duggan patent is extended or adjusted under 35 5,711,316 A 1/1998 Elsberry et al. 5,801, 188 A 9, 1998 Hassenbusch U.S.C. 154(b) by 265 days. 5,978,702 A 11/1999 Ward et al. This patent is Subject to a terminal dis 5,980,927 A * 1 1/1999 Nelson et al. ................. 424/425 claimer. 6,093,180 A 7/2000 Elsberry 6,180.355 B1 1/2001 Alexander et al. 6,521,259 B1* 2/2003 Chasin et al. ................. 424/489 (21) Appl. No.: 12/701.261 6,594,880 B2 7/2003 Elsberry 6,596,747 B2 7, 2003 BOS (22) Filed: Feb. 5, 2010 6,902,910 B2 6, 2005 Ni et al. 7.993,666 B2 * 8/2011 McKay et al. ................ 424/424 (65) Prior Publication Data 2002, 0071822 A1 6/2002 Uhrich 2003.0049256 A1 3/2003 Tobinick US 2010/O1590.15A1 Jun. 24, 2010 2003/OO77641 A1 4/2003 Laskowitz et al. 2003/01 19017 A1 6/2003 McSwiggen 2003. O157061 A1 8, 2003 Bennett 2003/017.5793 A1 9, 2003 Bennett et al. Related U.S. Application Data 2003.0185826 A1 10/2003 Tobinick 2004.0034357 A1 2/2004 Beane et al. (63) Continuation of application No. 1 1/460,012, filed on 2004/0052384 A1 3/2004 Ashley Jul. 26, 2006, which is a continuation-in-part of 2004/0265364 A1 12/2004 OZturk et al. application No. 10/972,157, filed on Oct. 22, 2004, 2005/0058696 A1* 3/2005 Donello et al. ............... 424/449 now abandoned. 2005.00757.01 A1 4/2005 Shafer 2005/0090549 A1 4/2005 Hildebrand et al. 2005/OO95246 A1 5, 2005 Shafer (51) Int. Cl. 2005/01297 31 A1 6/2005 Horres et al. A6 IK3 L/468 (2006.01) 2005/O180974 A1 8, 2005 Shafer A6 IK3I/00 (2006.01) A6 IK9/00 (2006.01) (Continued) A6 IK 9/16 (2006.01) FOREIGN PATENT DOCUMENTS A6 IK3I/85 (2006.01) A6 IK3I/92 (2006.01) EP 1 405 646 A2 4/2004 A6 IK3I/352 (2006.01) EP 1462111 A1 9, 2004 A6 IK3I/366 (2006.01) (Continued) A6 IK3I/38 (2006.01) OTHER PUBLICATIONS A6 IK3I/40 (2006.01) A6 IK3I/4402 (2006.01) Mercadante et al. Support. Care Cancer, vol. 7, 1999, pp. 47-50.* A6 IK3I/498 (2006.01) A6M 37/00 (2006.01) (Continued) (52) U.S. Cl. Primary Examiner — Jeffrey Stucker CPC ............... A6 IK3I/00 (2013.01); A61 K9/0019 Assistant Examiner — Stephen Gucker (2013.01); A61 K9/0024 (2013.01); A61 K 9/1647 (2013.01); A61 K3I/185 (2013.01); (74) Attorney, Agent, or Firm — Sorell Lenna & Schmidt A6 IK3I/192 (2013.01); A61 K3I/352 LLP (2013.01); A61 K3I/366 (2013.01); A61 K (57) ABSTRACT 31/381 (2013.01); A61 K3I/401 (2013.01); A6 IK3I/4168 (2013.01); A61 K3I/4402 Disclosed herein are systems and methods for contributing to (2013.01); A61 K3I/498 (2013.01); A61M the local treatment of pain. More specifically, the disclosed 37/0069 (2013.01); G0IN 2800/2842 (2013.01) systems and methods contribute to the local treatment pain by USPC ........... 514/385; 514/275; 514/277: 514/311; inhibiting the NFKB family of transcription factors. 514/419:514/423: 514/460: 514/529 14 Claims, 5 Drawing Sheets US 8,969,397 B2 Page 2 (56) References Cited Tobinick, Edward L., e al., Perispinal TNF-alpha Inhibition for Discogenic Pain, Swiss Med. Weekly, pp. 170-177, vol. 133, 2003. U.S. PATENT DOCUMENTS Malmberg, Annika B., et al., Antinociceptive Actions of Spinal Nonsteroidal Anti-inflammatory Agents on the Formalin Test in the 2005, 0182009 A1 8/2005 McSwiggen et al. Rat, The Journal of Pharmacology and Experimental Therapeutics, 2005/O1973 12 A1 9/2005 Fitzgerald et al. 1992, pp. 136-146, vol. 263. 2005/0209513 A1 9, 2005 Heruth et al. Ryu, Bo Rum, et al., The Novel Neuroprotective Action of Sulfasalazine through Blockade of NMDA Receptors, The Journal of FOREIGN PATENT DOCUMENTS Pharmacology and Experimental Therapeutics, 2003, pp. 48-56, vol. WO 97,42990 A1 11, 1997 305. WO 98.20868 A1 5, 1998 Gonzalez, M.I., et al., Evaluation of Selective NK1 Receptor Antago WO 98.475O2 A1 10, 1998 nist CI-1021 in Animal Models of Inflammatory and Neuropathic WO 02/09768 A2 2, 2002 Pain, The Journal of Pharmacology and Experimental Therapeutics, WO 02A38035 A2 5, 2002 WO O2/O7OOOT A1 9, 2002 2000, pp. 444-450, vol. 294. WO 02/074301 A1 9, 2002 Luo, Z. D., et al., Injury Type-specific Calcium Channel Alpha 2 WO 02/080893 A1 10, 2002 Delta-1 Subunit Up-regulation in Rat Neuropathic Pain Models Cor WO 02/085428 A2 10, 2002 relates with Antiallodynic Effects of Gabapentin. The Journal of WO 02/100330 A2 12/2002 Pharmacology and Experimental Therapeutics, 2002, pp. 1199-1205, WO O3,O26479 A2 4/2003 vol. 303. WO O3,O70897 A2 8, 2003 Luo, Z. D., et al., Upregulation of Dorsal Root Ganglion WO O3,O70970 A2 8, 2003 WO O3,O72135 A2 9, 2003 (Alpha)2(Delta) Calcium Channel Subunit and its Correlation with WO O3,083.061 A2 10, 2003 Allodynia in Spinal Nerve-injured Rats, The Journal of WO 2004/005551 A1 1, 2004 Neuroscience, 2001, pp. 1868-1875, vol. 21. WO 2004/032718 A2 4/2004 Jett, Mary-Frances, et al., Characterization of the Analgesic and WO 2004/039355 A1 5, 2004 Inti-inflammatory Activities of Ketorolac and Its Enantiomers in the WO 2004/066996 A1 8, 2004 Rat, The Journal of Pharmacology and Experimental Therapeutics, WO 2005/037323 A2 4/2005 1999, pp. 1288-1297, vol. 288. WO 2005/039.393 A2 5, 2005 Milligan, E. D., et al., Spinal Glia and Proinflammatory Cytokines WO 2005/046708 A1 5, 2005 Mediate Mirror-image Neuropathic Pain in Rats, The Journal of WO 2005/059134 A1 6, 2005 Neuroscience, 2003, pp. 1026-1040, vol. 2003. WO 2005/073164 A1 8, 2005 Parris, W. C.V., et al., Intrathecal Ketorolac Tromethamine Produces WO 2005/084366 A2 9, 2005 Analgesia after Chronic Constriction Injury of Sciatic Nerve in Rat, OTHER PUBLICATIONS Canadian Journal of Anaesthesia, 1996, pp. 867-870, vol. 43. Schafers, M., et al., Tumor Necrosis Factor-alpha induces Mechani Yoshioka et al. J. Palliat. Care, vol. 10, 1994 Spring, pp. 10-13 cal Allodynia after Spinal Nerve Ligation by Activation of P38 (Abstract Only).* MAPK in Primary Sensory Neurons, The Journal of Neuroscience, Sakaue, et al., NF-KB Decoy Supresses Cytokine Expression and 2003, pp. 2517-2521, vol. 23. Thermal Hyperalgesia in a Rat Neuropathic Pain Model. Sommer, c., et al., Etanercept Reduces Hyperalgesia in Experimental NeuroReport, Jul. 20, 2001, pp. 2079-2084, vol. 12, Issue 10. Painful Neuropathy, Journal of the Peripheral Nervous System, 2001, Lee, et al., Spinal NF-KB Activation Induces COX-2 Upregulation pp. 67-72, vol. 6. and Contributes to Inflammatory Pain Hypersensitivity, European Yaksh, T. L., et al., Intrathecal Ketorolac in Dogs and Rats, Toxico Journal of Neuroscience, 2004, pp. 3375-3381, vol. 19. logical Sciences, 2004, pp. 322-334, vol. 80. Tegeder, et al., Specific Inhibition of IKB Kinases Reduces Steed et al., Inactivation of TNF signalling by rationally designed Hyperalgesia in Inflammatory and Neuropathic Pain Models in Rats, dominant-negative TNF variants, Science 301: 1895-98, 2003. The Journal of Neuroscience, Feb. 18, 2004, pp. 1637-1645, vol. Jellinger and Stadelmann., Problems of cell death in neurodegenera 24(7). Nader, Nader D., et al., Clonidine Supresses Plasma and tion and Alzheimer's disease, J Alzheimer's Dis. 3:31-40, 2001. Cerebrospinal Fluid Concentrations of TNF-alpha During the Watterson et al., Discovery of new chemical classes of synthetic Perioperative Period, Anesthesia & Analgesia, 2001, pp. 363-369, ligands that Suppress neuroinflammatory responses, J Mol Neurosci vol. 93. 19:89-94, 2002. Dorn, Gabriele, et al., SiRNA Relieves Chronic Neuropathic Pain, Hirsch et al., The role of glial reaction and inflammation in Nucleic Acids Research, 2004, pp. 1-6, vol. 32, No. 5. Parkinson's Disease, Ann NY Acad Sci991:214-28, 2003. Igwe, Orisa J., Modulation of Peripheral Inflammation in Sensory Ito. Anti-interleukin-6 therapy for Crohn's disease, Curr Pharm Des Ganglia by Nuclear Factor KB Decoy oligodeoxynucleotide: 9:295-305, 2003. Involvement of SRC Kinase Pathway, Neuroscience Letters, 2005, pp. 114-119, vol. 381. * cited by examiner U.S. Patent US 8,969,397 B2 &#917 U.S. Patent Mar. 3, 2015 Sheet 2 of 5 US 8,969,397 B2 s s s ' ' ". ....... .''. ...: '...'......":::::: "...s.. .i. s H s s ... ." ":::::::::::::::::::: SS s ; ; SSS s s S. S S S S N S s s WI7S79-O % AOWI7777/M7CHLIMAM7 s: s SSNN s NIAS77O % AOWI7777/M7CHL/M/M7% U.S. Patent Mar. 3, 2015 Sheet 3 of 5 US 8,969,397 B2 1000 * p-0.05 900 a p<0.01 CÒS Co §S ·- CNSC; Contro/ Enbre? SulfaSalazine SulfaSalazine SulfaSalazine 3 mg/kg 0.2 mg/kg 1 mg/kg 5 mg/kg FIG, 4 US 8,969,397 B2 Vehicle Enbre/3 PDTC100 Sulindac 10 conidine 0.1 mg/kg mg/kg PD7C20 in kg Sulindac 2 mg/kg.
Load more

Recommended publications
  • Etats Rapides
    List of European Pharmacopoeia Reference Standards Effective from 2015/12/24 Order Reference Standard Batch n° Quantity Sale Information Monograph Leaflet Storage Price Code per vial Unit Y0001756 Exemestane for system suitability 1 10 mg 1 2766 Yes +5°C ± 3°C 79 ! Y0001561 Abacavir sulfate 1 20 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0001552 Abacavir for peak identification 1 10 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0001551 Abacavir for system suitability 1 10 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0000055 Acamprosate calcium - reference spectrum 1 n/a 1 1585 79 ! Y0000116 Acamprosate impurity A 1 50 mg 1 3-aminopropane-1-sulphonic acid 1585 Yes +5°C ± 3°C 79 ! Y0000500 Acarbose 3 100 mg 1 See leaflet ; Batch 2 is valid until 31 August 2015 2089 Yes +5°C ± 3°C 79 ! Y0000354 Acarbose for identification 1 10 mg 1 2089 Yes +5°C ± 3°C 79 ! Y0000427 Acarbose for peak identification 3 20 mg 1 Batch 2 is valid until 31 January 2015 2089 Yes +5°C ± 3°C 79 ! A0040000 Acebutolol hydrochloride 1 50 mg 1 0871 Yes +5°C ± 3°C 79 ! Y0000359 Acebutolol impurity B 2 10 mg 1 -[3-acetyl-4-[(2RS)-2-hydroxy-3-[(1-methylethyl)amino] propoxy]phenyl] 0871 Yes +5°C ± 3°C 79 ! acetamide (diacetolol) Y0000127 Acebutolol impurity C 1 20 mg 1 N-(3-acetyl-4-hydroxyphenyl)butanamide 0871 Yes +5°C ± 3°C 79 ! Y0000128 Acebutolol impurity I 2 0.004 mg 1 N-[3-acetyl-4-[(2RS)-3-(ethylamino)-2-hydroxypropoxy]phenyl] 0871 Yes +5°C ± 3°C 79 ! butanamide Y0000056 Aceclofenac - reference spectrum 1 n/a 1 1281 79 ! Y0000085 Aceclofenac impurity F 2 15 mg 1 benzyl[[[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxy]acetate
    [Show full text]
  • Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
    Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine
    [Show full text]
  • Influence of Co-Administrated Sinomenine on Pharmacokinetic
    Journal of Ethnopharmacology 99 (2005) 61–67 Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats Zhong Qiu Liu a, Hua Zhou a, Liang Liu a, Zhi Hong Jiang a, Yuen Fan Wong a, Ying Xie a, Xiong Cai a, Hong Xi Xu b, Kelvin Chan a, ∗ a School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, PR China b Hong Kong Jockey Club Institute of Chinese Medicine Limited, Hong Kong, PR China Received 10 August 2004; accepted 26 January 2005 Available online 20 March 2005 Abstract Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague–Dawley rats (n =6, 250–300 g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of sinomenine, the peak plasma concentration of paeoniflorin was elevated (P < 0.01), the peak time was delayed (P < 0.01), the AUC0–t was increased (P < 0.001), the mean residence time (MRT) was prolonged (P < 0.01), the CL was decreased (P < 0.01) and the Vd was reduced (P < 0.05).
    [Show full text]
  • Pharmaceutical and Veterinary Compounds and Metabolites
    PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES High quality reference materials for analytical testing of pharmaceutical and veterinary compounds and metabolites. lgcstandards.com/drehrenstorfer [email protected] LGC Quality | ISO 17034 | ISO/IEC 17025 | ISO 9001 PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES What you need to know Pharmaceutical and veterinary medicines are essential for To facilitate the fair trade of food, and to ensure a consistent human and animal welfare, but their use can leave residues and evidence-based approach to consumer protection across in both the food chain and the environment. In a 2019 survey the globe, the Codex Alimentarius Commission (“Codex”) was of EU member states, the European Food Safety Authority established in 1963. Codex is a joint agency of the FAO (Food (EFSA) found that the number one food safety concern was and Agriculture Office of the United Nations) and the WHO the misuse of antibiotics, hormones and steroids in farm (World Health Organisation). It is responsible for producing animals. This is, in part, related to the issue of growing antibiotic and maintaining the Codex Alimentarius: a compendium of resistance in humans as a result of their potential overuse in standards, guidelines and codes of practice relating to food animals. This level of concern and increasing awareness of safety. The legal framework for the authorisation, distribution the risks associated with veterinary residues entering the food and control of Veterinary Medicinal Products (VMPs) varies chain has led to many regulatory bodies increasing surveillance from country to country, but certain common principles activities for pharmaceutical and veterinary residues in food and apply which are described in the Codex guidelines.
    [Show full text]
  • Lack of the Age-Dependent Alteration in Mokuboito (Mu-Fang-Yi-Tang)
    Jan. 2012, Volume 9, No. 1 (Serial No. 86), pp. 1–8 Journal of US-China Medical Science, ISSN 1548-6648, USA D DAVID PUBLISHING Lack of the Age-Dependent Alteration in Mokuboito (Mu-Fang-Yi-Tang) Hiroyasu Satoh1 and Seiichiro Nishida2 1. Department of Health Science, Shitennoji University, Osaka 583-8501, Japan 2. Department of Pharmacology, Division of Traditional Herbal Medicine, Nara Medical University, Nara 634-8521, Japan Abstract: Objective: To compare the age-dependent vasodilating actions of Mokuboito, a kind of Kampo formulations, its ingredients. Methods: Rat aorta ring strips by pretreatment with 5 μM NE were used. Results: Sinomenine (a major constituent in Sinomenine acutum) at 100 μM dilated NE-induced vasoconstriction by 68.8±5.2% (n = 6, P < 0.01) in 10-weeks old rats, but only by 18.6±1.5% (n = 6, P < 0.01) in 65-weeks old rats. Sinomenine acutum (a main ingredient of Mokuboito)(0.3-3 mg/ml) showed only vasodilatations in 10- and 35-weeks old rats; at 3 mg/ml by 96.7±4.8% (n = 7, P < 0.01) in 10-weeks old rats. In 65-weeks old rats, however, Sinomenine acutum at low concentrations (0.03-0.3 mg/ml) constricted the aorta. The vasodilatation at 3 mg/ml was attenuated to 46.0±5.7% (n = 6, P < 0.01). Mokuboito also exerted the vasodilatation in all aged rats, although at low concentrations exhibited the vasoconstriction in higher aged rats. Mokuboito at 3 mg/ml dilated aorta by 98.9±2.8% (n = 7, P < 0.01) in 10-weeks and by 97.5±13.5% (n = 6, P < 0.01) in 65-weeks old rats.
    [Show full text]
  • (HIPK2) Attenuates Sepsis-Mediated Liver Injury by Restoring Autophag
    Jiang et al. Cell Death and Disease (2018) 9:847 DOI 10.1038/s41419-018-0838-9 Cell Death & Disease ARTICLE Open Access Overexpression of homeodomain- interacting protein kinase 2 (HIPK2) attenuates sepsis-mediated liver injury by restoring autophagy Zhengyu Jiang1,LulongBo1,YanMeng1,ChenWang2, Tianxing Chen3,4, Changli Wang1,XiyaYu1 and Xiaoming Deng1 Abstract Sepsis is the leading cause of death in intensive care units worldwide. Autophagy has recently been shown to protect against sepsis-induced liver injury. Here, we investigated the roles of homeodomain-interacting protein kinase 2 (HIPK2) in the molecular mechanism of sepsis-induced liver injury. HIPK2 expression was reduced in sepsis-induced liver injury, and HIPK2 overexpression increased the survival rate and improved caecal ligation and puncture (CLP)- induced liver injury by reducing serum and liver aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels in mice with sepsis. HIPK2 overexpression significantly decreased CLP-induced release of inflammatory cytokines into the serum and attenuated oxidative stress-associated indicators in mice with CLP-induced liver injury, whereas HIPK2 knockdown produced the opposite results, suggesting that HIPK2 is a negative regulator of sepsis. Furthermore, HIPK2 overexpression inhibited lipopolysaccharide (LPS)-induced apoptosis of primary 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; hepatocytes, increased the autophagic flux, and restored both autophagosome and autolysosome formation in the livers of CLP-induced mice by suppressing calpain signalling. Importantly, HIPK2 overexpression reduced the elevated cytosolic Ca2+ concentration in LPS-treated primary hepatocytes by interacting with calpain 1 and calmodulin. Finally, several anti-inflammatory drugs, including resveratrol, aspirin, vitamin E and ursolic acid, significantly increased the levels of the HIPK2 mRNA and protein by modulating promoter activity and the 3′-UTR stability of the HIPK2 gene.
    [Show full text]
  • Unlocking the Non-Ige-Mediated Pseudo-Allergic Reaction Puzzle with Mas-Related G-Protein Coupled Receptor Member X2 (MRGPRX2)
    cells Review Unlocking the Non-IgE-Mediated Pseudo-Allergic Reaction Puzzle with Mas-Related G-Protein Coupled Receptor Member X2 (MRGPRX2) Mukesh Kumar, Karthi Duraisamy and Billy-Kwok-Chong Chow * School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China; [email protected] (M.K.); [email protected] (K.D.) * Correspondence: [email protected]; Tel.: +852-2299-0850; Fax: +852-2559-9114 Abstract: Mas-related G-protein coupled receptor member X2 (MRGPRX2) is a class A GPCR ex- pressed on mast cells. Mast cells are granulated tissue-resident cells known for host cell response, allergic response, and vascular homeostasis. Immunoglobulin E receptor (Fc"RI)-mediated mast cell activation is a well-studied and recognized mechanism of allergy and hypersensitivity reac- tions. However, non-IgE-mediated mast cell activation is less explored and is not well recognized. After decades of uncertainty, MRGPRX2 was discovered as the receptor responsible for non-IgE- mediated mast cells activation. The puzzle of non-IgE-mediated pseudo-allergic reaction is unlocked by MRGPRX2, evidenced by a plethora of reported endogenous and exogenous MRGPRX2 ag- onists. MRGPRX2 is exclusively expressed on mast cells and exhibits varying affinity for many molecules such as antimicrobial host defense peptides, neuropeptides, and even US Food and Drug Administration-approved drugs. The discovery of MRGPRX2 has changed our understanding of mast cell biology and filled the missing link of the underlying mechanism of drug-induced MC degranulation and pseudo-allergic reactions. These non-canonical characteristics render MRGPRX2 Citation: Kumar, M.; Duraisamy, K.; Chow, B.-K.-C.
    [Show full text]
  • LGC Standards Pharmacopoeial Reference Standards 2014
    LL CTS INKSP RODUTO A L P ITH W WEBSHO LGC Standards Pharmacopoeial reference standards 2014 FOR STANDARDS WITH CofA SEE OUR CATALOGUE: PHARMACEUTICAL IMPURITIES AND PRIMARY REFERENCE STANDARDS LGC Quality – ISO Guide 34 • GMP/GLP • ISO 9001 • ISO/IEC 17025 • ISO/IEC 17043 Pharmaceutical impurities Code Product CAS No. CS Price Unit Adiphenine Hydrochloride O LGC Standards N O MM1172.00 Adiphenine Hydrochloride 50-42-0 A 250mg HCl Pharmaceutical impurities and Adrenaline Tartrate OH H OH O OH primary reference standardsMM0614.00 2014 N OH Adrenaline Tartrate 51-42-3 A 500mg OH OH O OH OH H MM0614.02 L-Adrenaline 51-43-4 A 500mg OH N OH Imp. C (EP) as Hydrochloride: 1-(3,4-Di- O H OH MM0614.13 hydroxyphenyl)-2-(methylamino)ethanone 62-13-5 A 100mg N HCl Hydrochloride (Adrenalone Hydrochloride) OH (1R)-1-(3,4-Dihydroxyphenyl)-2- OH O S O MM0614.01 methylaminoethanesulphonic Acid H 78995-75-2 A 100mg OH N (Adrenaline -Sulphonate) OH Alanine NH2 MM0566.00 Alanine 56-41-7 A 500mg OH O Imp. A (Pharmeuropa): (2 S)-2-Aminobutanedioic Acid O NH 2 MM0567.00 OH (Aspartic Acid) 56-84-8 A 500mg OH O Albendazole O H MM0382.00 Albendazole N O 54965-21-8 A 500mg N H S N Imp. A (EP): 5-(Propylsulphanyl)-1H- H MM0382.01 N 80983-36-4 A 100mg NH2 benzimidazol-2-amine S N O H Imp. B (EP): Methyl [5-Propylsulphinyl)- N O MM0382.02 N 54029-12-8 A 100mg H 1H-benzimidazol-2-yl]carbamate S N O O H Imp.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley Et Al
    US 2014O144429A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley et al. (43) Pub. Date: May 29, 2014 (54) METHODS AND DEVICES FOR COMPOUND (60) Provisional application No. 61/887,045, filed on Oct. DELIVERY 4, 2013, provisional application No. 61/831,992, filed on Jun. 6, 2013, provisional application No. 61/794, (71) Applicant: E-NICOTINE TECHNOLOGY, INC., 601, filed on Mar. 15, 2013, provisional application Draper, UT (US) No. 61/730,738, filed on Nov. 28, 2012. (72) Inventors: Martin Wensley, Los Gatos, CA (US); Publication Classification Michael Hufford, Chapel Hill, NC (US); Jeffrey Williams, Draper, UT (51) Int. Cl. (US); Peter Lloyd, Walnut Creek, CA A6M II/04 (2006.01) (US) (52) U.S. Cl. CPC ................................... A6M II/04 (2013.O1 (73) Assignee: E-NICOTINE TECHNOLOGY, INC., ( ) Draper, UT (US) USPC ..................................................... 128/200.14 (21) Appl. No.: 14/168,338 (57) ABSTRACT 1-1. Provided herein are methods, devices, systems, and computer (22) Filed: Jan. 30, 2014 readable medium for delivering one or more compounds to a O O Subject. Also described herein are methods, devices, systems, Related U.S. Application Data and computer readable medium for transitioning a Smoker to (63) Continuation of application No. PCT/US 13/72426, an electronic nicotine delivery device and for Smoking or filed on Nov. 27, 2013. nicotine cessation. Patent Application Publication May 29, 2014 Sheet 1 of 26 US 2014/O144429 A1 FIG. 2A 204 -1 2O6 Patent Application Publication May 29, 2014 Sheet 2 of 26 US 2014/O144429 A1 Area liquid is vaporized Electrical Connection Agent O s 2.
    [Show full text]
  • Analytical Reference Standards
    Cerilliant Quality ISO GUIDE 34 ISO/IEC 17025 ISO 90 01:2 00 8 GM P/ GL P Analytical Reference Standards 2 011 Analytical Reference Standards 20 811 PALOMA DRIVE, SUITE A, ROUND ROCK, TEXAS 78665, USA 11 PHONE 800/848-7837 | 512/238-9974 | FAX 800/654-1458 | 512/238-9129 | www.cerilliant.com company overview about cerilliant Cerilliant is an ISO Guide 34 and ISO 17025 accredited company dedicated to producing and providing high quality Certified Reference Standards and Certified Spiking SolutionsTM. We serve a diverse group of customers including private and public laboratories, research institutes, instrument manufacturers and pharmaceutical concerns – organizations that require materials of the highest quality, whether they’re conducing clinical or forensic testing, environmental analysis, pharmaceutical research, or developing new testing equipment. But we do more than just conduct science on their behalf. We make science smarter. Our team of experts includes numerous PhDs and advance-degreed specialists in science, manufacturing, and quality control, all of whom have a passion for the work they do, thrive in our collaborative atmosphere which values innovative thinking, and approach each day committed to delivering products and service second to none. At Cerilliant, we believe good chemistry is more than just a process in the lab. It’s also about creating partnerships that anticipate the needs of our clients and provide the catalyst for their success. to place an order or for customer service WEBSITE: www.cerilliant.com E-MAIL: [email protected] PHONE (8 A.M.–5 P.M. CT): 800/848-7837 | 512/238-9974 FAX: 800/654-1458 | 512/238-9129 ADDRESS: 811 PALOMA DRIVE, SUITE A ROUND ROCK, TEXAS 78665, USA © 2010 Cerilliant Corporation.
    [Show full text]
  • Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) That Modulate Drug Membrane Permeation and Pre-Systemic Metabolism
    pharmaceutics Review Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism Bianca Peterson, Morné Weyers , Jan H. Steenekamp, Johan D. Steyn, Chrisna Gouws and Josias H. Hamman * Centre of Excellence for Pharmaceutical Sciences (Pharmacen™), North-West University, Potchefstroom 2520, South Africa; [email protected] (B.P.); [email protected] (M.W.); [email protected] (J.H.S.); [email protected] (J.D.S.); [email protected] (C.G.) * Correspondence: [email protected]; Tel.: +27-18-299-4035 Received: 11 December 2018; Accepted: 24 December 2018; Published: 16 January 2019 Abstract: Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial mucosal layers, which have to be crossed by drug molecules in order to exert a therapeutic effect. Another barrier is the pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes. Although the nasal, buccal and pulmonary routes of administration avoid the first-pass effect, they are still dependent on absorption of drug molecules across the mucosal surfaces to achieve systemic drug delivery. Bioenhancers (drug absorption enhancers of natural origin) have been identified that can increase the quantity of unchanged drug that appears in the systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism.
    [Show full text]
  • Recent Applications of Capillary Electrophoresis in the Determination of Active Compounds in Medicinal Plants and Pharmaceutical Formulations
    molecules Review Recent Applications of Capillary Electrophoresis in the Determination of Active Compounds in Medicinal Plants and Pharmaceutical Formulations Marcin Gackowski 1,* , Anna Przybylska 1 , Stefan Kruszewski 2 , Marcin Koba 1 , Katarzyna M ˛adra-Gackowska 3 and Artur Bogacz 4 1 Department of Toxicology and Bromatology, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, A. Jurasza 2 Street, PL–85089 Bydgoszcz, Poland; [email protected] (A.P.); [email protected] (M.K.) 2 Biophysics Department, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Jagiello´nska13 Street, PL–85067 Bydgoszcz, Poland; [email protected] 3 Department of Geriatrics, Faculty of Health Sciences, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Skłodowskiej Curie 9 Street, PL–85094 Bydgoszcz, Poland; [email protected] 4 Department of Otolaryngology and Oncology, Faculty of Medicine, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Skłodowskiej Curie 9 Street, PL–85094 Bydgoszcz, Poland; [email protected] Citation: Gackowski, M.; Przybylska, * Correspondence: [email protected] A.; Kruszewski, S.; Koba, M.; M ˛adra-Gackowska,K.; Bogacz, A. Abstract: The present review summarizes scientific reports from between 2010 and 2019 on the use Recent Applications of Capillary of capillary electrophoresis to quantify active constituents (i.e., phenolic compounds, coumarins, Electrophoresis in the Determination protoberberines, curcuminoids, iridoid glycosides, alkaloids, triterpene acids) in medicinal plants and of Active Compounds in Medicinal herbal formulations. The present literature review is founded on PRISMA guidelines and selection Plants and Pharmaceutical criteria were formulated on the basis of PICOS (Population, Intervention, Comparison, Outcome, Formulations.
    [Show full text]