DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. N0.: US 2014/0221426 A1 Gerk Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. N0.: US 2014/0221426 A1 Gerk Et Al US 20140221426A1 (19) United States (12) Patent Application Publication (10) Pub. N0.: US 2014/0221426 A1 Gerk et al. (43) Pub. Date: Aug. 7, 2014 (54) SELECTIVE METABOLIC APPROACH TO A61K 31/216 (2006.01) INCREASING ORAL BIOAVAILABILITY OF A61K 31/09 (2006.01) PHENYLEPHRINE AND OTHER PHENOLIC A61K 31/05 (2006.01) BIOACTIVITIES A61K 31/353 (2006.01) A61K 31/4525 (2006.01) (71) Applicant: VIRGINIA COMMONWEALTH A61 K 31/3 75 (2006.01) UNIVERSITY, Richmond, VA (US) A61K 31/121 (2006.01) _ _ _ (52) US. Cl. (72) Inventorsl Ph_lll_lP M- Gerk’ Rthmond, VA (Us); CPC ........... .. A61K 31/137 (2013.01); A61K 31/3 75 Wllllam H- Fa", R10hm°nda VA (Us); (2013.01); A61K 31/235 (2013.01); A61K J"sellh K- thter’ Rlchmond, VA (Us) 31/11 (2013.01); A61K 31/085 (2013.01); _ A61K 31/121 (2013.01); A61K 31/09 (21) APP1~ NO" 14/345,689 (2013.01); A61K31/05 (2013.01); A61K . _ 31/353 (2013.01);A61K31/4525 (2013.01); (22) PCT Filed. Sep. 27, 2012 A61K31/216 (201301) USPC ......... .. 514/321' 514/653' 514/474' 514/544' ( 86 ) PCT N 0 .: PCT/U52012/057588 ’ ’ 514/456;’ 514/532’ § 371 (0X1), Related US“ Application Data Presystemic metabolism in intestine of bioactives such as (60) Provisional application No. 61/539,530, ?led on Sep. phenylephrine 1? avoided by administering a Sllbject (human 27, 2011, provisional application No. 61/544,396, 0r 21111111211) the bloactlve(e-g-,Pheny1ephr1ne)1n comblnatlon ?led on Oct 7, 201 1_ With one or more inhibitors of sulfation (e.g., sulfotransferase enzymes aka SULTs). This can also be enhanced be co Publication Classi?cation administering inhibitors of monoamine oxidases aka, MAOs, and uridine diphosphate glucoronysl transferases, aka UGTs. (51) Int. Cl. Preferably the inhibitors are GRAS compounds. The one or A61K 31/137 (2006.01) more inhibitor compounds inhibit the enzymes responsible A61K 31/235 (2006.01) for rapid presystemic metabolism, thus allowing the bioac A61K 31/11 (2006.01) tives (e. g., phenylephrine) to be more readily absorbed intact A61K 31/085 (2006.01) into the circulatory system. Patent Application Publication Aug. 7, 2014 Sheet 1 0f 4 US 2014/0221426 A1 Synthesis of Phenyiephrine 3-O-Sulfate OH F NHCH a i F o 3 1.TFA20,20C,15mm. ff 0 F O >+F OH N F \ phenylephrine CH3 2‘ 803*Py1‘; pyridine OH 90cc, 130mm F NOF 0 F OH 0 HF 3. aq. 1M KHco3 NHCH3 N\ F 25 0C,0vernighl CH3 0 /O K 28% \s // Q(3 phenylephrine 3-O-suifate, potassium salt FIGURE 1 Patent Application Publication Aug. 7, 2014 Sheet 2 0f4 US 2014/0221426 A1 Figure 2A. Inhibition of 4-Methylumbellifer0ne Metabolism . 4-Methylumbelliferone A 4-Methylumbelliferonemetabolized (as%ofsolutionwithoutcells) Figure 28. Inhibition of 1-Naphthol Metabolism. 1-Naphthol 1~Naphtholmetabolized (as%ofsolutionwithoutcells) Patent Application Publication Aug. 7, 2014 Sheet 3 of4 US 2014/0221426 A1 Figure 2C. Inhibition of Raspberry Ketone Metabolism. Rasketone (raspberry ketone) 1 239.mewo~=on§wE x.mi:oréow*0305.?3:00 Figure 2D. Inhibition of Pinoresinol Metabolism. Pinoresinoi w8642 moooéoo Q Patent Application Publication Aug. 7, 2014 Sheet 4 of 4 US 2014/0221426 A1 Figure 2E. inhibition of Magnoiol Metabolism. Magnolol 80- ~1— 60 Magnololmetabollzed (as%ofsolutionwithoutcells) 40 ii 1* 2 Figure 2F. Inhibition of a-Mangostin Metabolism. a-Mangostin A a-Mangostmmetaboilzed (as%ofsolutionwithoutcells) US 2014/0221426 A1 Aug. 7, 2014 SELECTIVE METABOLIC APPROACH TO inhibiting or reducing the rate of biotransforrnation of drugs INCREASING ORAL BIOAVAILABILITY OF in the liver or intestines. Qazi does not identify the extract as PHENYLEPHRINE AND OTHER PHENOLIC including GRAS compounds. BIOAC TIVITIES [0010] US. Pat. No. 6,180,666 to Wacher et al. describes [0001] Portions of this invention were made using funding orally co-administering a compound of interest with a gallic from the National Institutes of Health (NIH/NCMHD Grant acid ester such as octyl gallate, propyl gallate, lauryl gallate, and methyl gallate. Gallic acid is a trihydroxybenzoic acid, a No. 1P60-MD002256), and the US. Government has certain rights in this invention. type of organic phenolic acid found in plants such as gallnuts, sumac, witch hazel, tea leaves, and oak bark. The gallic acid BACKGROUND ester is purportedly present in order to inhibit biotransforma tions of drugs that are carried out e.g. by cytochromes P450. [0002] 1. Field of the Invention The esters are described as GRAS compounds. [0003] The invention is generally related to increasing the [0011] US. Pat. No. 6,121,234 to Benet et al., describes a bioavailability of bioactive compounds which are adminis method for purportedly increasing bioavailability and reduc tered or taken orally, and more particularly, to using com ing inter- and intra-individual variability of an orally admin pounds which are generally regarded as safe (GRAS), par istered hydrophobic pharmaceutical compound. In Benet, the ticularly certain phenolic compounds, to prevent or decrease pharmaceutical compound is orally co-administered with an pre-systemic or systemic metabolism or clearance of the bio essential oil or essential oil component. Benet suggests that active compounds. the role of the essential oil may be to inhibit drug biotrans [0004] 2. Description of the PriorArt formation in the gut. Essential oils are described as GRAS [0005] Increasing the bioavailablity of compounds pro compounds. vided to a subject to treat various diseases has been a subject [0012] US patent application 2003/0215462 to Wacher et of intense investigation for a number of years. Furthermore, al. describes using UDP-glucuronosyltrasnsferase (UGT) there have been a number of approaches that have employed inhibitors to increase the bioavailability orally administered compositions that include a drug in combination with sub drugs. Wacher suggests the formulation may be used with stances that are Generally Regarded As Safe (GRAS) com 2-methoxyestradiol, raloxifene, irinotecan, SN-38, estradiol, pounds. labetalol, dilevalol, zidovudine (AZT) and morphine. The [0006] US. Pat. No. 5,972,382 to Majeed et al. teaches UDP-inhibitors are generally natural products and include compositions and methods for the improvement of gas epicatechin gallate, epigallocatechin gallate, octyl gallate, trointestinal absorption and systemic utilization of nutrients propyl gallate, quercetin, tannic acid, benzoin gum, capsai and nutritional supplements by combining them with pip cin, dihydrocapsaicin, eugenol, gallocatechin gallate, erine, an alkaloid derived from black pepper. Maj eed does not geraniol, menthol, menthyl acetate, naringenin, allspice berry discuss the delivery of drugs per se, and piperine is not a oil, N-vanillylnonanamide, clovebud oil, peppermint oil, sili GRAS compound. binin, and silymarin. Wacher does not list resveratrol and [0007] US. Pat. No. 7,576,124 to Harris describes “?rst phenylephrine as exemplary drugs, nor are the GRAS sub pass” inhibiting furocoumarin compounds that are purport stances propyl paraben, vanillin, vitamin C and curcumin edly safe and effective. The furocoumarins are citrus-derived identi?ed as being useful in Wacher. The objective of the substances prepared from, e.g., grapefruit. Harris does not Wacher technology appears to be the identi?cation of speci?c identify which components of pre-systemic metabolism are combinations of drugs and inhibitors that work well together. inhibited, but the cytochrome P450 family of enzymes is Wacher notes that “ . a compound that inhibits the glucu referenced. The furocoumarins are not described as GRAS. ronidation of one substrate does not necessarily prevent the [0008] US. Pat. No. 7,125,564 to Chen et al. discusses glucuronidation of all UGT substrates . ”. problems associated with ?rst-pass degradation of bioactive [0013] US patent applications 2006/0040875 and 2009/ treatment compounds, and teaches the use of water-soluble 0093467 to Oliver et al. describe UGT2B inhibitors that can complexes with glycyrrhizin, which is the main sweet-tasting increase the bio-availability of drugs. Speci?cally named compounds from licorice root. Glycyrrhizin is described as inhibitors are natural products such as capillarisin, isorham GRAS. Chen does not indicate that glycyrrhizin can inhibit netin, [3-naphtho?avone, (x-naphtho?avone, hesperetin, terpi ?rst pass metabolism; rather, Chen discusses having the com neol, (+)-limonene, [3-myrcene, swertiamarin, eriodictyol, positions parenterally administered to avoid the ?rst-pass cineole, apigenin, baicalin, ursolic acid, isovitexin, lauryl effect. alcohol, puerarin, trans-cinnamaldehyde, 3-phenylpropyl [0009] US. Pat. No. 7,070,814 to Qazi et al. teaches com acetate, isoliquritigenin, paeoni?orin, gallic acid, genistein, positions which are purportedly bioenhancing/bioavailabil glycyrrhizin, protocatechuic acid, ethyl myristate, and ity-facilitating. These compositions include an extract and/or umbelliferone. Suggested drugs for which bioavailability can at least one bioactive fraction from the Cuminum cyminum be increased include morphine, naloxone, nalorphine, oxy plant (i.e., the plant from which the spice cumin is derived). morphone, hydromorphone, dihydromorphine, codeine, nal This extract is combined with drugs, nutrients, vitamins, trexone, naltrindole, nalbuphine and buprenorphine. The nutraceuticals, herbal drugs/products, micro nutrients, and focus of Oliver is on the delivery of analgesics. antioxidants, along with pharmaceutically acceptable addi [0014] US patent application 2010/0087493 to Kaivosaari tives/excipients. Similar to the Majeed patent, Qazi
Load more

Recommended publications
  • Chemoprotective Effects of Flaxseed Lignans Enterodiol And
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Texas A&M Repository CHEMOPROTECTIVE EFFECTS OF FLAXSEED LIGNANS ENTERODIOL AND ENTEROLACTONE IN NON-TRANSFORMED COLONOCYTES A Thesis by CHRISTINA ALISON CURRY Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Chair of Committee, Clinton Allred Committee Members, Joseph Awika Jenna Anding Head of Department, Boon Chew December 2015 Major Subject: Nutrition Copyright 2015 Christina Alison Curry ABSTRACT Previous epidemiological studies have shown that colon cancer incidence is correlated to diet and estrogen status. Phytoestrogens are molecules with similar structures to estrogen that occur naturally in plants. There is in vitro and in vivo evidence that phytoestrogens in the diet can inhibit carcinogenesis. The phytoestrogenic mammalian lignans enterolactone (EL) and enterodiol (ED) in flaxseed have been shown to be effective in decreasing tumor incidence in carcinogenic models, but there is little data regarding their effects in non-malignant cells. The following studies used a non- transformed cell line of young adult mouse colonocytes (YAMC) to determine the protective effects of ED and EL in chemoprevention. Our results demonstrate that low levels of EL (1µM) and ED (5µM) are effective at significantly reducing cell growth and increasing apoptosis. These treatments also regulated transcription via significant differences in gene levels related to apoptosis and cell cycle progression. The data collected demonstrate some of the physiological effects of EL and ED on the cellular and molecular level.
    [Show full text]
  • Phytoestrogens : Daidzein, Enterodiol, Enterolactone, Equol, Geinstein, O-Desmethylangolensin Matrix: Urine Method: HPLC-ESI-MS/MS Method No: 4069.03
    Laboratory Procedure Manual Analyte: Phytoestrogens : Daidzein, Enterodiol, Enterolactone, Equol, Geinstein, O-Desmethylangolensin Matrix: Urine Method: HPLC-ESI-MS/MS Method No: 4069.03 Revised: March 2018 as performed by: Nutritional Biomarkers Branch (NBB) Division of Laboratory Sciences (DLS) National Center for Environmental Health (NCEH) contact: James L. Pirkle, M.D., Ph.D. Director, Division of Laboratory Sciences Important Information for Users CDC periodically refines these laboratory methods. It is the responsibility of the user to contact the person listed on the title page of each write-up before using the analytical method to find out whether any changes have been made and what revisions, if any, have been incorporated. Phytoestrogen NHANES 2013-2014 This document details the Lab Protocol for testing the items listed in the following table. This method file describes measurements of U1PHYTO_H_R and U2PHYTO_H_R. One method was used to measure both the 24 hour urine phytoestrogen, 1st urine collection and 24 hour urine phytoestrogen, 2nd urine collection. However, these results are released as 2 separate data files. Variable File Name SAS Label (and SI units) Name Daidzein, Urine 1st collection UR1DAZ (ng/mL) o-Desmethylangolensin, Urine 1st UR1DMA Collection (ng/mL) UR1EQU Equol, Urine 1st Collection (ng/mL) Enterodiol, Urine 1st Collection UR1ETD (ng/mL) Enterolactone, Urine 1st Collection UR1ETL (ng/mL) Genistein, Urine 1st Collection UR1GNS (ng/mL) U1PT_H_R Daidzein, Urine 2nd collection U2PT_H_R UR2DAZ (ng/mL) o-Desmethylangolensin, Urine 2nd UR2DMA Collection (ng/mL) UR2EQU Equol, Urine 2nd Collection (ng/mL) Enterodiol, Urine 2nd Collection UR2ETD (ng/mL) Enterolactone, Urine 2nd Collection UR2ETL (ng/mL) Genistein, Urine 2nd Collection UR2GNS (ng/mL) 2 of 54 Phytoestrogen NHANES 2013-2014 1.
    [Show full text]
  • Trans-Resveratrol [501-36-0]
    trans-Resveratrol [501-36-0] Review of Toxicological Literature March 2002 trans-Resveratrol [501-36-0] Review of Toxicological Literature Prepared for Scott Masten, Ph.D. National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, North Carolina 27709 Contract No. N01-ES-65402 Submitted by Karen E. Haneke, M.S. Integrated Laboratory Systems P.O. Box 13501 Research Triangle Park, North Carolina 27709 March 2002 Toxicological Summary for trans-Resveratrol [501-36-0] 03/2002 Executive Summary Nomination trans-Resveratrol was nominated for toxicology studies by the National Institute of Environmental Health Sciences (NIEHS) based on the widespread human exposure to resveratrol through natural dietary sources and dietary supplement use, and concern that it has not been sufficiently evaluated for potential toxicological effects. Non-Toxicological Data General Description: trans-Resveratrol is a polyphenol that occurs naturally in grapes, peanuts, and a number of other plants. It is found in foods/drinks made from grapes and peanuts, and also in a number of herbal remedies, both alone and as part of plant extracts. Commercial Availability, Production, and Uses: trans-Resveratrol is produced commercially by several companies. A commercial extraction method involves using alcohol and water to produce trans­ resveratrol from Polygonum cuspidatum. Resveratrol compounds may be produced or extracted for research purposes by treating cell suspension cultures of grapes with a natural substance from a fungus. Resveratrol compounds have long been found in herbal medicines. Health claims of oral dietary supplements containing trans-resveratrol include protection from free-radical damage, inhibition of arthritic inflammation, inhibition of the cyclooxygenase-2 enzyme, protection of blood vessels, protection against cardiovascular disease and cancer, and alleviation of menopausal symptoms.
    [Show full text]
  • Urinary and Serum Concentrations of Seven Phytoestrogens in a Human Reference Population Subset
    Journal of Exposure Analysis and Environmental Epidemiology (2003) 13, 276–282 r 2003 Nature Publishing Group All rights reserved 1053-4245/03/$25.00 www.nature.com/jea Urinary and serum concentrations of seven phytoestrogens in a human reference population subset LIZA VALENTI´ N-BLASINI, BENJAMIN C. BLOUNT, SAMUEL P. CAUDILL, AND LARRY L. NEEDHAM National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA Diets rich in naturally occurring plant estrogens (phytoestrogens) are strongly associated with a decreased risk for cancer and heart disease in humans. Phytoestrogens have estrogenic and, in some cases, antiestrogenic and antiandrogenic properties, and may contribute to the protective effect of some diets. However, little information is available about the levels of these phytoestrogens in the general US population. Therefore, levels of phytoestrogenswere determined in urine (N ¼ 199) and serum (N ¼ 208) samples taken from a nonrepresentative subset of adults who participated in NHANES III, 1988– 1994. The phytoestrogens quantified were the lignans (enterolactone, enterodiol, matairesinol); the isoflavones (genistein, daidzein, equol, O- desmethylangolensin); and coumestrol (urine only). Phytoestrogens with the highest mean urinary levels were enterolactone (512 ng/ml), daidzein(317 ng/ ml), and genistein (129 ng/ml). In serum, the concentrations were much less and the relative order was reversed, with genistein having the highest mean level (4.7 ng/ml), followed by daidzein (3.9 ng/ml) and enterolactone (3.6 ng/ml). Highly significant correlations of phytoestrogen levels in urineand serum samples from the same persons were observed for enterolactone, enterodiol, genistein, and daidzein. Determination of phytoestrogen concentrations in large study populations will give a better insight into the actual dietary exposure to these biologically active compounds in the US population.
    [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]
  • 1.25 Lignans: Biosynthesis and Function
    1.25 Lignans: Biosynthesis and Function NORMAN G. LEWIS and LAURENCE B. DAVIN Washington State University, Pullman, WA, USA 0[14[0 INTRODUCTION 539 0[14[1 DEFINITION AND NOMENCLATURE 539 0[14[2 EVOLUTION OF THE LIGNAN PATHWAY 531 0[14[3 OCCURRENCE 534 0[14[3[0 Li`nans in {{Early|| Land Plants 534 0[14[3[1 Li`nans in Gymnosperms and An`iosperms "General Features# 536 0[14[4 OPTICAL ACTIVITY OF LIGNAN SKELETAL TYPES AND LIMITATIONS TO THE FREE RADICAL RANDOM COUPLING HYPOTHESIS 536 0[14[5 707? STEREOSELECTIVE COUPLING] DIRIGENT PROTEINS AND E!CONIFERYL ALCOHOL RADICALS 541 0[14[5[0 Diri`ent Proteins Stipulate Stereoselective Outcome of E!Coniferyl Alcohol Radical Couplin` in Pinoresinol Formation 541 0[14[5[1 Clonin` of the Gene Encodin` the Diri`ent Protein and Recombinant Protein Expression in Heterolo`ous Systems 543 0[14[5[2 Sequence Homolo`y Comparisons 543 0[14[5[3 Comparable Systems 543 0[14[5[4 Perceived Biochemical Mechanism of Action 546 0[14[6 PINORESINOL METABOLISM AND ASSOCIATED METABOLIC PROCESSES 547 0[14[6[0 Sesamum indicum] "¦#!Piperitol\ "¦#!Sesamin\ and "¦#!Sesamolinol Synthases 547 0[14[6[1 Magnolia kobus] Pinoresinol and Pinoresinol Monomethyl Ether O!Methyltransferase"s# 550 0[14[6[2 Forsythia intermedia and Forsythia suspensa 551 0[14[6[2[0 "¦#!Pinoresinol:"¦#!lariciresinol reductase 552 0[14[6[2[1 "−#!Secoisolariciresinol dehydro`enase 554 0[14[6[2[2 Matairesinol O!methyltransferase 556 0[14[6[3 Linum usitatissimum] "−#!Pinoresinol:"−#!Lariciresinol Reductase and "¦#!Secoisolariciresinol Glucosyltransferase"s# 557
    [Show full text]
  • ANTIOXIDANT PROPERTIES of FLAXSEED LIGNANS USING in VITRO MODEL SYSTEMS a Thesis Submitted to the College of Graduate Studies A
    ANTIOXIDANT PROPERTIES OF FLAXSEED LIGNANS USING IN VITRO MODEL SYSTEMS A Thesis Submitted to the College of Graduate Studies and Research in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the College of Pharmacy and Nutrition of the University of Saskatchewan Saskatoon, Saskatchewan Canada By Farah Hosseinian Copyright Farah Hosseinian April 2006 All Rights Reserved The author claims copyright. Use shall not be made of the material contained herein without proper acknowledgment, as indicated on the copyright page. i PERMISION TO USE In presenting this thesis in partial fulfillment of the requirements for a Postgraduate degree from the University of Saskatchewan, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for copying of this thesis in any manner, in whole or in part, for scholarly purposes may be granted by the professor or professors who supervised my thesis work or, in their absence, by the Dean of the College in which my thesis work was done. It is understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without permission. It is also understood that due recognition shall be given to me and to the University of Saskatchewan in any scholarly use made of any material in my thesis. Requests for permission to copy or to make other use of material in this thesis, in whole or in parts, should be addressed to: Head College of Pharmacy and Nutrition University of Saskatchewan 110 Science Place Saskatoon, SK S7N 5C9 Canada ii 1.0 ABSTRACT The major objectives of this study were to investigate the antioxidant properties of flaxseed lignans secoisolariciresinol (SECO 2) and secoisolariciresinol diglycoside (SDG 1) and their major oxidative compounds using 2,2'-azobis(2- amidinopropane) dihydrochloride (AAPH 47) in an in vitro model of lipid peroxidation.
    [Show full text]
  • 3. Food Chemistry & Biotechnology 3.1. Lectures
    Chem. Listy, 102, s265–s1311 (2008) Food Chemistry & Biotechnology 3. FOOD CHEMISTRY been femented for 10 days at 10 °c under semiaerobic condi- & BIOTECHNOLOGY tions or 4–6 weeks at 10 °c under anaerobic conditions. Second cultivation medium: the sterile vinea drinks were inoculated by studied yeast strains and cultuivated at 3.1. Lectures 20 °c for 10 days under semiaerobic conditions. the samples were than sensorially evaluated by a group L01 NONSACCHAROMYCES YEAST IN GRAPE of degustators. the same samples were than analysed by gas MUST – ADVANTAGE OR SPOILAGE? chromatography for the aroma compounds production. each sample was analysed on the Gc MS (Shimadzu QP 2010) JAROSLAVA Kaňuchová PátKováa, EMÍLIA equipment and also on the Gc FiD equipment (Gc 8000 ce Breierováb and INGRID vajcziKová instruments). aInstitute for viticulture and enology of SARC two methods of sample preparation were done: Matuškova 25, 831 01 Bratislava, Slovak republic, the samples (20 ml) were extracted by ether (2 ml), and bInstitute of ChemistrySAS, Dúbravská cesta 9, 845 38 Brati- centrifuged prior to analysis. the etheric extract was used for slava, Slovak republic, analysis (liquid – liquid extraction). this method was used [email protected] for higher alcohols (propanol, isoamylacohol, ethyl ester and higher alcoholos esters) determination Introduction the samples were extracted by tenaq (solid phase mic- the fresh grape must consists of spontaneous microf- roextraction) and than 10 min sampling according to6. this lora formed from 90 to 99 % by yeasts. the most important method was used for monoterpenic compounds determina- genus is without doubt Saccharomyces cerevisiae which is tion.the same column and the same conditions were used by responsible for successive fermentation and good wine qua- both analysis: column: DB WaX 30 m, 0.25 × 0.25, tempe- lity.
    [Show full text]
  • Natural and Semi-Synthetic Compounds with Biocidal Activity Against Arthropods of Public Health Importance
    AN ABSTRACT OF THE DISSERTATION OF Mohammad A. Khasawneh for the degree of Doctor of PhilosoDhy in Chemistry presented on December 5, 2003. Title: Natural and Semi-Synthetic Compounds With Biocidal Activity Against Arthropods Of Public Health Importance. Abstract approved:Redacted for privacy JosephfJ Karchesy This study identified new compounds with pest control activities. The two sources of candidates that were followed here were the main heartwood extract of Alaska Yellow Cedar (AYC) constituents and several semi-synthetic counterparts. Five compounds were isolated and identified for the first time in AYC heartwood in this research: two monoterpenes, two sesquiterpenes, and one lignan. The two monoterpenes were (1 S)-2-oxo-3-p-menthenol (41) and (4R)-4- hydroxy-4-isopropyl-cyclohex-l-enecarboxylic acid (63). The two sesquiterpenes were (5 S,7R, 1 OR, 11 R)-eudesm-4(l 4)-ene- 11,1 2-diol (46) and (4R,5S,7R)- 1(10)- eremohpilen-1 1,12-diol (59). The lignan was (1R,2S,5R,6S)-2,6-bis-(3,5- dimethoxy-4-hydroxyphenyl)-3 ,7-dioxabicyclo- [3.3.01 Qctafle, (67). Structures for these compounds were confirmedon the basis of spectroscopic techniques such as 1- and 2-D NMR, high resolution MS and JR. The pest control activity studies of 15 compounds isolatedor semi- synthesized from AYC heartwood were conducted at the Centers for Disease Control and Prevention (CDC). Two types of studieswere conducted - short-term (24h) and residual (over 1-4 weeks) activity for application against threetypes of pests related to human health- nymphal I. scapularis ticks, adult X cheopis fleas and adult Ae.
    [Show full text]
  • Synthetic Secoisolariciresinol Diglucoside Attenuates Established Pain, Oxidative Stress and Neuroinflammation in a Rodent Model
    antioxidants Article Synthetic Secoisolariciresinol Diglucoside Attenuates Established Pain, Oxidative Stress and Neuroinflammation in a Rodent Model of Painful Radiculopathy Sonia Kartha 1, Christine L. Weisshaar 1, Ralph A. Pietrofesa 2, Melpo Christofidou-Solomidou 2 and Beth A. Winkelstein 1,3,* 1 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; [email protected] (S.K.); [email protected] (C.L.W.) 2 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; [email protected] (R.A.P.); [email protected] (M.C.-S.) 3 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA * Correspondence: [email protected] Received: 18 October 2020; Accepted: 25 November 2020; Published: 30 November 2020 Abstract: Painful cervical radiculopathy is characterized by chronic neuroinflammation that lowers endogenous antioxidant responses leading to the development of oxidative stress and pain after neural trauma. Therefore, antioxidants such as secoisolariciresinol diglucoside (SDG), that promote antioxidant signaling and reduce oxidative damage may also provide pain relief. This study investigated if repeated systemic administration of synthetic SDG after a painful root compression reduces the established pain, oxidative stress and spinal glial activation that are typically evident. SDG was administered on days 1–3 after compression and the extent of oxidative damage in the dorsal root ganglia (DRG) and spinal cord was measured at day 7 using the oxidative stress markers 8-hydroxguanosine (8-OHG) and nitrotyrosine. Spinal microglial and astrocytic activation were also separately evaluated at day 7 after compression. In addition to reducing pain, SDG treatment reduced both spinal 8-OHG and nitrotyrosine, as well as peripheral 8-OHG in the DRG.
    [Show full text]
  • WO 2018/002916 Al O
    (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 2018/002916 Al 04 January 2018 (04.01.2018) W !P O PCT (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C08F2/32 (2006.01) C08J 9/00 (2006.01) kind of national protection available): AE, AG, AL, AM, C08G 18/08 (2006.01) 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, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, PCT/IL20 17/050706 HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (22) International Filing Date: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 26 June 2017 (26.06.2017) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 246468 26 June 2016 (26.06.2016) IL kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (71) Applicant: TECHNION RESEARCH & DEVEL¬ UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, OPMENT FOUNDATION LIMITED [IL/IL]; Senate TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, House, Technion City, 3200004 Haifa (IL).
    [Show full text]
  • Phyto-Oestrogens and Chaste Tree Berry
    omens H f W ea o l l th a Leo et al., J Women’s Health Care 2014, 3:5 n C r a u r e o DOI: 10.4172/2167-0420.1000182 J Journal of Women's Health Care ISSN: 2167-0420 Research Article Open Access Phyto-Oestrogens and Chaste Tree Berry: A New Option in the Treatment of Menopausal Disorders Vincenzo De Leo*, Valentina Cappelli, Alessandra Di Sabatino and Giuseppe Morgante Molecular Medicine and Development Department, Obstetrics and Gynecology Clinic, University of Siena, Italy Abstract For a woman, menopause represents a transitional phase from a fertile to a non-fertile age, in which there is a gradual reduction in ovarian function accompanied by a gradual cessation of oestrogen production. The clinical presentation can involve a series of disorders, including hot flushes with episodes of sweating, particularly at night, palpitations, changes in sleep-wake rhythm, irritability, anxiety and mood changes, vaginal dryness due to a process of progressive atrophy with thinning of the outer and inner labia, reduction of vascularisation and elastic fibres, and decreased sexual desire; subsequently, Many women use alternative therapies to treat hot flushes and other menopausal symptoms. The purpose of this review is to summarize current information on the efficacy and safety of phytoestrogens and the herbal medicine. Given the importance that these symptoms assume for the woman, not only for the perceived quality of life, but also for the increased risk of developing all the diseases, all the treatments adopted for menopausal women are directed primarily to resolving vasomotor disorder Keywords: Menopause; Vasomotor symptoms; Hot flushes; Phyto- fibres, and decreased sexual desire; subsequently, the process of atrophy oestrogens; Magnolia; Chaste tree berry also affects the epidermis with thin, pale skin that is easily susceptible to bacterial and viral infections.
    [Show full text]