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US009314527B2 (12) United States Patent (10) Patent No.: US 9,314,527 B2 Cottrell et al. (45) Date of Patent: *Apr. 19, 2016 (54) TRANSDERMAL DELIVERY PATCH 9/7061 (2013.01); A61K 9/7084 (2013.01); (71) Applicant: Phosphagenics Limited, Clayton, A61 K3I/355 (2013.01); A61K47/24 Victoria (AU) SE7 8E.O. (72) Inventors: Jeremy Cottrell, Caulfield South (AU); ( .01): ( .01): (2013.01) Giacinto Gaetano, South Melbourne (AU); Mahmoud El-Tamimy, Meadow (58) Field of Classification Search Heights (AU); Nicholas Kennedy, None Boronia (AU); Paul David Gavin, See application file for complete search history. Chadstone (AU) (56) References Cited (73) Assignee: Phosphagenics Limited, Victoria (AU) (*) Notice: Subject to any disclaimer, the term of this U.S. PATENT DOCUMENTS patent is extended or adjusted under 35 2,407,823. A 9, 1946 Fieser U.S.C. 154(b) by 0 days. 2.457,932 A 1/1949 Solmssen et al. This patent is Subject to a terminal dis- (Continued) claimer. (21) Appl. No.: 14/550,514 FOREIGN PATENT DOCUMENTS ppl. No.: 9 (22) Filed: Nov. 21, 2014 A 3.3 5.83 (65) Prior Publication Data (Continued) Related U.S. Application Data Gianello et al. Subchronic Oral Toxicity Study of Mixed Tocopheryl (63) Continuation of application No. 14/086,738, filed on Phosphates in Rates, International Journal of Toxicology, 26:475 Nov. 21, 2013, now abandoned, which is a 490; 2007.* continuation of application No. 13/501,500, filed as (Continued) application No. PCT/AU2011/000358 on Mar. 30, 2011, now Pat. No. 8,652,511. Primary Examiner — Robert A Wax (60) Provisional application No. -
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Gastroparesis and Nutrition: the Art
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #99 Carol Rees Parrish, R.D., M.S., Series Editor Gastroparesis and Nutrition: The Art Carol Rees Parrish Stacey McCray Gastroparesis, or delayed gastric emptying, is a complex disorder characterized by nausea, vomiting, early satiety, and abdominal discomfort. Complications of gastro- paresis not only lead to increased morbidity, increased time spent in the hospital, and significant nutritional deficits, but also impact the overall quality of life of those affected. This article will review the anatomy and physiology of gastroparesis, discuss some of the treatment options available, and outline recommendations for nutritional monitoring and therapy for patients with gastroparesis. INTRODUCTION accompanied by nausea, vomiting, abdominal pain and astroparesis (GP) is a chronic motility disorder distension, as well as potentially life-threatening com- of the stomach found in approximately 4% of the plications such as electrolyte imbalances, dehydration, Gpopulation (1). Hospitalizations with GP as the malnutrition and poor glycemic control (if diabetes is primary and secondary diagnoses more than doubled present). In those with GP and diabetes mellitus (DM), between 1995 and 2004 (2). Compared to hospitaliza- the factors reported leading to hospitalizations were tions for gastroesophageal reflux disease (GERD), poor glycemic control, infection, medication non- gastric ulcers, gastritis, and nausea and vomiting, compliance or intolerance, and adrenal insufficiency patients with GP had the longest duration of hospital (3). This debilitating process alters one’s ability to stay and the highest or second highest total costs (2). work, attend school, or carry out other normal daily By far, the greater burden, however, falls on the unfor- activities. -
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ATP, 489 Absolute Configuration Benzomotphans, 204 Levotphanol
Index AIDA, 495 Affinity labeling, analogs of (Cont.) cAMP, 409, 489 motphine,448 ATP, 409, 489 naltrexone, 449 [3H] ATP, 489 norlevotphanol,449 Absolute configuration normetazocine, 181 benzomotphans, 204 norpethidine, 232 levotphanol, 115 oripavine, 453 methadone and analogs, 316 oxymotphone, 449 motphine, 86 K-Agonists, 179,405,434 phenoperidine, 234 Aid in Interactive Drug Analysis, 495 piperazine derivatives, 399 [L-Ala2] dermotphin, 363 prodines and analogs, 272 [D-Ala, D-Leu] enkephalin (DADL), 68, 344 sinomenine, 28, 115 [D-Ala2 , Bugs] enkephalinamide, 347, 447 viminol, 400 [D-Ala2, Met'] enkephalinamide, 337, 346, Ac 61-91,360 371,489 Acetylcholine, 5, 407 [D-Ala2]leu-enkephalin, 344, 346, 348 Acetylcholine analogs, 186, 191 [D-Ala2] met-enkephalin, 348 l-Acetylcodeine, 32 [D-Ala2] enkephalins, 347 Acetylmethadols (a and (3) Alfentanil, 296 maintenance of addicts by a-isomer, 304, 309 (±)-I1(3-Alkylbenzomotphans, 167, 170 metabolism, 309 11(3-Alkylbenzomotphans, 204 N-allyl and N-CPM analogs, 310, 431 7-Alkylisomotphinans, 146 stereochemistry, 323 N-Alkylnorketobemidones, 431 synthesis, 309 N-Alkylnorpethidines, 233 X-ray crystallography, 327 N-Allylnormetazocine, 420 6-Acetylmotphine, receptor binding, 27 N-Allylnormotphine, 405 Acetylnormethadol, 323 N-Allylnorpethidine, 233 8(3-Acyldihydrocodeinones, 52 3-Allylprodines (a and (3), 256 14-Acyl-4,5-epoxymotphinans, 58 'H-NMR and stereochemistry, 256 7-Acylhydromotphones, 128 X-ray crystallography, 256 Addiction, 4 N-Allylnormetazocine, 420 Adenylate cyclase, 6, 409, 413, 424, -
United States Patent [191 [1 1] 4,045,440 Rapoport Et A1
United States Patent [191 [1 1] 4,045,440 Rapoport et a1. [45] Aug. 30, 1977 [54] METHOD OF PRODUCING THEBAINE Primary Examiner-Donald G. Daus FROM CODEINE AND ORIPAVINE FROM Assistant Examiner-Diana G. Rivers MORPHINE Attorney, Agent, or Firm-John S. Roberts, Jr.; Norman [75] Inventors: Henry Rlpoport; Randy B. Barber, J. Latker; Thomas G. Ferris both of Berkeley, Calif. [57] ABSTRACT [73] Assignee: The United States of America as represented by the Department of A method of producing thebaine from codeine and Health, Education and Welfare, oripavine from morphine which comprises (a) produc Washington, DC. ing the 0-6 methyl ethers from codeine and morphine using potassium hydride and methyl iodide as the O [21] Appl.No.: 724,018 alkylation agents and (b) subsequently oxidizing the [22] Filed: Sept. 16, 1976 respective 0-6 methyl ethers of codeine and morphine to shift from allylic structure to a dienol ether structure [51] Int. Cl.2 .......................................... .. C07D 489/02 using an oxidizing amount of M1102 in tetrahydrofuran [52] US. Cl. .................................................. .. 260/285 to produce thebaine from codeine and oripavine from [58] Field of Search ....................................... .. 260/285 morphine. In the case of morphine, it is preferable to [56] References Cited protect the 0-3 position by acetylation prior to the oxi dizing step. Both the etheri?cation and oxidizing steps FOREIGN PATENT DOCUMENTS are carried out under a protecting blanket such as nitro 1,133,392 7/l962 Germany gen and the reactions are carried out preferably under atmospheric pressure and ambient temperature with the OTHER PUBLICATIONS exception of the etheri?cation affecting the 0-6 position Barber et al., J. -
WO 2018/152334 Al 23 August 2018 (23.08.2018) W !P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/152334 Al 23 August 2018 (23.08.2018) W !P O PCT (51) International Patent Classification: (US). YUCEL, Tuna; 28 Monmouth Avenue, Medford, A61K 9/107 (2006.01) A61K 31/352 (2006.01) MA 02155 (US). BOYLAN, Nicholas, J.; 215 Green A61K 47/26 (2006.01) A61K 9/48 (2006.01) Street, Boylston, MA 01505 (US). A61K 47/14 (2006.01) A61K 9/00 (2006.01) (74) Agent: EISENSCHENK, Frank, C. et al; Saliwanchik, A61K 31/05 (2006 .01) A61P 25/06 (2006 .0 1) Lloyd & Eisenschenk, P.O. Box 142950, Gainesville, FL (21) International Application Number: 32614-2950 (US). PCT/US2018/018382 (81) Designated States (unless otherwise indicated, for every (22) International Filing Date: kind of national protection available): AE, AG, AL, AM, 15 February 2018 (15.02.2018) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (25) Filing Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (26) Publication Language: English HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (30) Priority Data: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/459,086 15 February 2017 (15.02.2017) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/546,149 16 August 2017 (16.08.2017) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, (71) Applicant: MOLECULAR INFUSIONS, LLC [US/US]; TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
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WO 2016/185468 Al 24 November 2016 (24.11.2016) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/185468 Al 24 November 2016 (24.11.2016) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/164 (2006.01) A61K 31/485 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 31/4468 (2006.01) A61P 25/04 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/IL20 16/0505 19 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 17 May 2016 (17.05.2016) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/164,618 2 1 May 2015 (21.05.2015) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: THERAPIX BIOSCIENCES LTD.