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(12) United States Patent (10) Patent No.: US 9.421,180 B2 Zielinski Et Al
USOO9421 180B2 (12) United States Patent (10) Patent No.: US 9.421,180 B2 Zielinski et al. (45) Date of Patent: Aug. 23, 2016 (54) ANTIOXIDANT COMPOSITIONS FOR 6,203,817 B1 3/2001 Cormier et al. .............. 424/464 TREATMENT OF INFLAMMATION OR 6,323,232 B1 1 1/2001 Keet al. ............ ... 514,408 6,521,668 B2 2/2003 Anderson et al. ..... 514f679 OXIDATIVE DAMAGE 6,572,882 B1 6/2003 Vercauteren et al. ........ 424/451 6,805,873 B2 10/2004 Gaudout et al. ....... ... 424/401 (71) Applicant: Perio Sciences, LLC, Dallas, TX (US) 7,041,322 B2 5/2006 Gaudout et al. .............. 424/765 7,179,841 B2 2/2007 Zielinski et al. .. ... 514,474 (72) Inventors: Jan Zielinski, Vista, CA (US); Thomas 2003/0069302 A1 4/2003 Zielinski ........ ... 514,452 Russell Moon, Dallas, TX (US); 2004/0037860 A1 2/2004 Maillon ...... ... 424/401 Edward P. Allen, Dallas, TX (US) 2004/0091589 A1 5, 2004 Roy et al. ... 426,265 s s 2004/0224004 A1 1 1/2004 Zielinski ..... ... 424/442 2005/0032882 A1 2/2005 Chen ............................. 514,456 (73) Assignee: Perio Sciences, LLC, Dallas, TX (US) 2005, 0137205 A1 6, 2005 Van Breen ..... 514,252.12 2005. O154054 A1 7/2005 Zielinski et al. ............. 514,474 (*) Notice: Subject to any disclaimer, the term of this 2005/0271692 Al 12/2005 Gervasio-Nugent patent is extended or adjusted under 35 et al. ............................. 424/401 2006/0173065 A1 8/2006 BeZwada ...................... 514,419 U.S.C. 154(b) by 19 days. 2006/O193790 A1 8/2006 Doyle et al. -
USP Statement on Validation of DNA Test Methods for Regulating the Quality of Herbal Supplements
USP Statement on Validation of DNA Test Methods for Regulating the Quality of Herbal Supplements U.S. PHARMACOPEIAL CONVENTION The United States Pharmacopeial Convention Urges Scientific Validation of DNA Test Methods for Regulating the Quality of Herbal Supplements (Rockville, MD – April 16, 2015) – In response to an agreement announced between the New York State Attorney General (NYAG) and GNC Holdings, Inc. (GNC) the United States Pharmacopeial Convention (USP), an independent, science based, standards setting organization and publishers of the United States Pharmacopeia-National Formulary (USP-NF), an official compendia of quality standards for dietary supplements sold in the U.S., issued the following statement: Statement by Gabriel Giancaspro, PhD – Vice President –Foods, Dietary Supplement and Herbal Medicines United States Pharmacopeial Convention (USP) “As a science-based standards-setting organization, the United States Pharmacopeial Convention (USP) has a keen interest in adopting emerging technologies to ensure the test methods and quality standards included in the United States Pharmacopeia-National Formulary (USP-NF) are current and reflect the state of the industry. DNA testing including DNA Barcoding, is just one example of a technology that has been recently added to the USP-NF. As of December 2014, DNA-based identification methods are included in the official USP chapter <563> Identification of Articles of Botanical Origin. However, this method is not yet referenced in a USP-NF monograph (quality standard) for a specific ingredient or product. That is because USP quality standards are specific for each ingredient, product and dosage form and the standards we develop include only those test methods that have been scientifically validated and shown to be fit for purpose. -
Research Publications by DISTINCTIONS Any Scientist of Pakistan in Last 10 Year and SERVICES Secretary General, the Chemical Society of Pakistan
CV and List of Publications PROF. DR. MUHAMMAD IQBAL CHOUDHARY (Hilal-e-Imtiaz, Sitara-e-Imtiaz, Tamgha-ei-Imtiaz) International Center for Chemical and Biological Sciences (H. E. J. Research Institute of Chemistry, Dr. Panjwani Center for Molecular Medicine and Drug Research) University of Karachi, Karachi-75270 Pakistan Tel: (92-21) 34824924, 34824925 Fax: 34819018, 34819019 E-mail: [email protected] Web Page: www.iccs.edu Biodata and List of Publications Pag No. 2 MUHAMMAD IQBAL CHOUDHARY (Hilal-e-Imtiaz, Sitara-e-Imtiaz, Tamgha-e-Imtiaz) D-131, Phase II, D. O. H. S., Malir Cant., Karachi-75270, Pakistan Ph.: 92-21-4901110 MAILING INTERNATIONAL CENTER FOR CHEMICAL AND BIOLOGICAL SCIENCES ADDRESS (H. E. J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research) University of Karachi Karachi-74270, Pakistan Tel: (92-21) 34824924-5 Fax: (92-21) 34819018-9 Email: [email protected] Web: www.iccs.edu DATE OF BIRTH September 11, 1959 (Karachi, Pakistan) EDUCATION Doctor of Science (D.Sc.) (University of Karachi ) 2005 Ph.D. (Organic Chemistry) 1987 H. E. J. Research Institute of Chemistry University of Karachi, Karachi-75270, Pakistan Thesis Title: "The Isolation and Structural Studies on Some Medicinal Plants of Pakistan, Buxus papillosa, Catharanthus roseus, and Cissampelos pareira." M.Sc. (Organic Chemistry) 1983 University of Karachi, Karachi-75270, Pakistan B.Sc. (Chemistry, Biochemistry, Botany) 1980 University of Karachi, Karachi-75270, Pakistan AWARDS & Declared as the top most scientist (Number 1) among 1,650 HONORS scientists of Pakistan in all disciplines / fields of science and technology (year 2012) by the Pakistan Council for Science and Technology (Ministry of Science and Technology), Pakistan. -
Quantitative High-Throughput Profiling of Environmental Chemicals and Drugs That Modulate Farnesoid X Receptor
OPEN Quantitative High-Throughput Profiling of SUBJECT AREAS: Environmental Chemicals and Drugs that SCREENING SMALL MOLECULES Modulate Farnesoid X Receptor Chia-Wen Hsu1, Jinghua Zhao1, Ruili Huang1, Jui-Hua Hsieh2, Jon Hamm3, Xiaoqing Chang3, Keith Houck4 Received & Menghang Xia1 27 June 2014 Accepted 1National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, 2Division of the National 29 August 2014 Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 3Integrated Laboratory Systems, Inc., Morrisville, NC, 4U.S. Environmental Protection Agency, Research Triangle Park, NC. Published 26 September 2014 The farnesoid X receptor (FXR) regulates the homeostasis of bile acids, lipids, and glucose. Because endogenous chemicals bind and activate FXR, it is important to examine which xenobiotic compounds Correspondence and would disrupt normal receptor function. We used a cell-based human FXR b-lactamase (Bla) reporter gene assay to profile the Tox21 10K compound collection of environmental chemicals and drugs. requests for materials Structure-activity relationships of FXR-active compounds revealed by this screening were then compared should be addressed to against the androgen receptor, estrogen receptor a, peroxisome proliferator-activated receptors d and c, and M.X. ([email protected]. the vitamin D receptor. We identified several FXR-active structural classes including anthracyclines, gov) benzimidazoles, dihydropyridines, pyrethroids, retinoic acids, and vinca alkaloids. Microtubule inhibitors potently decreased FXR reporter gene activity. Pyrethroids specifically antagonized FXR transactivation. Anthracyclines affected reporter activity in all tested assays, suggesting non-specific activity. These results provide important information to prioritize chemicals for further investigation, and suggest possible modes of action of compounds in FXR signaling. -
Curcumin in Autoimmune and Rheumatic Diseases
nutrients Review Curcumin in Autoimmune and Rheumatic Diseases Melissa Yang, Umair Akbar and Chandra Mohan * Department of Biomedical Engineering, University of Houston, 3517 Cullen Blvd, Room 2004, Houston, TX 77204, USA; [email protected] (M.Y.); [email protected] (U.A.) * Correspondence: [email protected]; Tel.: 713-743-3709 Received: 29 March 2019; Accepted: 24 April 2019; Published: 2 May 2019 Abstract: Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care. -
USP Reference Standards Catalog
Last Updated On: January 6, 2016 USP Reference Standards Catalog Catalog # Description Current Lot Previous Lot CAS # NDC # Unit Price Special Restriction 1000408 Abacavir Sulfate R028L0 F1L487 (12/16) 188062-50-2 $222.00 (200 mg) 1000419 Abacavir Sulfate F0G248 188062-50-2 $692.00 Racemic (20 mg) (4-[2-amino-6-(cyclo propylamino)-9H-pur in-9yl]-2-cyclopenten e-1-methanol sulfate (2:1)) 1000420 Abacavir Related F1L311 F0H284 (10/13) 124752-25-6 $692.00 Compound A (20 mg) ([4-(2,6-diamino-9H- purin-9-yl)cyclopent- 2-enyl]methanol) 1000437 Abacavir Related F0M143 N/A $692.00 Compound D (20 mg) (N6-Cyclopropyl-9-{( 1R,4S)-4-[(2,5-diami no-6-chlorpyrimidin- 4-yloxy)methyl] cyclopent-2-enyl}-9H -purine-2,6-diamine) 1000441 Abacavir Related F1L318 F0H283 (10/13) N/A $692.00 Compound B (20 mg) ([4-(2,5-diamino-6-c Page 1 Last Updated On: January 6, 2016 USP Reference Standards Catalog Catalog # Description Current Lot Previous Lot CAS # NDC # Unit Price Special Restriction hloropyrimidin-4-yla mino)cyclopent-2-en yl]methanol) 1000452 Abacavir Related F1L322 F0H285 (09/13) 172015-79-1 $692.00 Compound C (20 mg) ([(1S,4R)-4-(2-amino -6-chloro-9H-purin-9 -yl)cyclopent-2-enyl] methanol hydrochloride) 1000485 Abacavir Related R039P0 F0J094 (11/16) N/A $692.00 Compounds Mixture (15 mg) 1000496 Abacavir F0J102 N/A $692.00 Stereoisomers Mixture (15 mg) 1000500 Abacavir System F0J097 N/A $692.00 Suitability Mixture (15 mg) 1000521 Acarbose (200 mg) F0M160 56180-94-0 $222.00 (COLD SHIPMENT REQUIRED) 1000532 Acarbose System F0L204 N/A $692.00 Suitability -
Small Molecules in Solution Has Rarely Been Reported, However, As a General Guide We Recommend Storage in DMSO at -20°C
(Z)-Guggulsterone Small Molecules Retinoic acid receptor (RAR) pathway inhibitor; Inhibits farnesoid X receptor (FXR) Catalog # 73702 1 mg Product Description (Z)-Guggulsterone is a plant steroid found in the resin of the guggul plant Commiphora mukul that acts as a selective antagonist of farnesoid X receptor (FXR; Cui et al.). It decreases chenodeoxycholic acid (CDCA)-induced FXR activation (IC ₅₀ = 10 µM) in the presence of 100 µM CDCA (Urizar et al.; Cui et al.). Molecular Name: (Z)-Guggulsterone Alternative Names: Not applicable CAS Number: 39025-23-5 Chemical Formula: C₂₁H₂₈O₂ Molecular Weight: 312.5 g/mol Purity: ≥ 95% Chemical Name: (8R,9S,10R,13S,14S,17Z)-17-ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15- decahydrocyclopenta[a]phenanthrene-3,16-dione Structure: Properties Physical Appearance: A crystalline solid Storage: Product stable at -20°C as supplied. Protect product from prolonged exposure to light. For long-term storage store with a desiccant. For product expiry date, please contact [email protected]. Solubility: · DMSO ≤ 800 µM · Absolute ethanol ≤ 3.2 µM · DMF ≤ 30 mM For example, to prepare a 10 mM stock solution in DMF, resuspend 1 mg in 320 μL of DMF. Prepare stock solution fresh before use. Information regarding stability of small molecules in solution has rarely been reported, however, as a general guide we recommend storage in DMSO at -20°C. Aliquot into working volumes to avoid repeated freeze-thaw cycles. The effect of storage of stock solution on compound performance should be tested for each application. Compound has low solubility in aqueous media. -
Guggulsterones and Levels
Cholesterol, Guggulsterones and levels. Because normal levels of serum lipids, Bile Production including cholesterol, are supported by increased circulating thyroid hormones, it is believed guggul Much of the cholesterol made by your liver is uti- Guggulsterones works by stimulating the thyroid gland, in addition lized to create bile, a substance used in digestion to its effects on bile production. to emulsify fats. Because excess cholesterol and triglycerides are excreted from our bodies in the Clinically Effective Dosage form of bile, it is important to support the liver’s bile-producing mechanism. According to several clinical studies, the amount of guggulsterones used to maintain Natural Support for Research shows that certain guggul compounds— normal cholesterol levels is 75 mg per day, guggulsterones—help maintain cholesterol levels when taken with a diet low in saturated fats. Cholesterol Health in the normal range and act at the farnesoid X This is the daily dose delivered by SOURCE receptor (FXR) to promote bile production. NATURALS GUGGULSTERONES. Guggulsterones appear to be farnesoid X receptor (FXR) antagonists. FXR is a bile acid receptor. If A Wellness Revolution in FXR is activated, this results in down-regulation Cardiovascular Care of the amount of bile acids produced by the liver. Bile is made out of cholesterol, which gets used up At a time when our cardiovascular health faces when bile is produced. When bile levels are high, numerous lifestyle challenges, research into the the production of more bile is slowed through remarkable heart-supportive properties of the oday’s lifestyle, with its high-fat, processed food diet, lack of exercise, and negative feedback of the FXR pathway. -
Potential of Guggulsterone, a Farnesoid X Receptor Antagonist, In
Exploration of Targeted Anti-tumor Therapy Open Access Review Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer Sosmitha Girisa , Dey Parama , Choudhary Harsha , Kishore Banik , Ajaikumar B. Kunnumakkara* Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India *Correspondence: Ajaikumar B. Kunnumakkara, Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India. [email protected]; [email protected] Academic Editor: Gautam Sethi, National University of Singapore, Singapore Received: August 8, 2020 Accepted: September 14, 2020 Published: October 30, 2020 Cite this article: Girisa S, Parama D, Harsha C, Banik K, Kunnumakkara AB. Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer. Explor Target Antitumor Ther. 2020;1:313-42. https://doi.org/10.37349/ etat.2020.00019 Abstract Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one such plant which has been used to cure various ailments in traditional systems of medicine. -
Dietary Supplements Compendium Volume 1
2015 Dietary Supplements Compendium DSC Volume 1 General Notices and Requirements USP–NF General Chapters USP–NF Dietary Supplement Monographs USP–NF Excipient Monographs FCC General Provisions FCC Monographs FCC Identity Standards FCC Appendices Reagents, Indicators, and Solutions Reference Tables DSC217M_DSCVol1_Title_2015-01_V3.indd 1 2/2/15 12:18 PM 2 Notice and Warning Concerning U.S. Patent or Trademark Rights The inclusion in the USP Dietary Supplements Compendium of a monograph on any dietary supplement in respect to which patent or trademark rights may exist shall not be deemed, and is not intended as, a grant of, or authority to exercise, any right or privilege protected by such patent or trademark. All such rights and privileges are vested in the patent or trademark owner, and no other person may exercise the same without express permission, authority, or license secured from such patent or trademark owner. Concerning Use of the USP Dietary Supplements Compendium Attention is called to the fact that USP Dietary Supplements Compendium text is fully copyrighted. Authors and others wishing to use portions of the text should request permission to do so from the Legal Department of the United States Pharmacopeial Convention. Copyright © 2015 The United States Pharmacopeial Convention ISBN: 978-1-936424-41-2 12601 Twinbrook Parkway, Rockville, MD 20852 All rights reserved. DSC Contents iii Contents USP Dietary Supplements Compendium Volume 1 Volume 2 Members . v. Preface . v Mission and Preface . 1 Dietary Supplements Admission Evaluations . 1. General Notices and Requirements . 9 USP Dietary Supplement Verification Program . .205 USP–NF General Chapters . 25 Dietary Supplements Regulatory USP–NF Dietary Supplement Monographs . -
Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway
International Journal of Molecular Sciences Article Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway Patricia Rodríguez Castaño 1,2, Shaheena Parween 1,2 and Amit V Pandey 1,2,* 1 Pediatric Endocrinology, Diabetology, and Metabolism, University Children’s Hospital Bern, 3010 Bern, Switzerland; [email protected] (P.R.C.); [email protected] (S.P.) 2 Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland * Correspondence: [email protected]; Tel.: +41-31-632-9637 Received: 5 September 2019; Accepted: 16 September 2019; Published: 17 September 2019 Abstract: Turmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of the Curcuma longa and is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wound healing, anti-inflammatory, and anti-carcinogenic activities. While curcuminoids have been studied for many years, not much is known about their effects on steroid metabolism. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the effect of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. When using 10 µg/mL of curcuminoids, both the 17α-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, only a mild reduction in CYP21A2 activity was observed. Furthermore, CYP19A1 activity was also reduced up to ~20% of control when using 1–100 µg/mL of curcuminoids in a dose-dependent manner. Molecular docking studies confirmed that curcumin could dock onto the active sites of CYP17A1, CYP19A1, as well as CYP21A2. -
WO 2013/163758 Al 7 November 2013 (07.11.2013) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2013/163758 Al 7 November 2013 (07.11.2013) P O P C T (51) International Patent Classification: (72) Inventor; and A61K 31/416 (2006.01) C12Q 1/00 (2006.01) (71) Applicant : BOYD, Shelley Romayne [CA/CA]; Unit A61P 27/02 (2006.01) A61B 3/10 (2006.01) 2106, 112 George Street, Toronto, Ontario M5A 2M5 (CA). (21) International Application Number: PCT/CA2013/050335 (74) Agents: MARLES, Jennifer A. et al; 480-601 West Cor dova Street, Vancouver, British Columbia V6B 1G1 (CA). (22) International Filing Date: 30 April 2013 (30.04.2013) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (25) Filing Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (26) Publication Language: English BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (30) Priority Data: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, 61/640,854 1 May 2012 (01.05.2012) US KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 61/641,393 2 May 2012 (02.05.2012) US ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 61/693,226 24 August 2012 (24.08.2012) us NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, 61/792,436 15 March 2013 (15.03.2013) us RW, SC, 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.