YMC HPLC Columns Applications Notebook
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Table S1: Sensitivity, Specificity, PPV, NPV, and F1 Score of NLP Vs. ICD for Identification of Symptoms for (A) Biome Developm
Table S1: Sensitivity, specificity, PPV, NPV, and F1 score of NLP vs. ICD for identification of symptoms for (A) BioMe development cohort; (B) BioMe validation cohort; (C) MIMIC-III; (D) 1 year of notes from patients in BioMe calculated using manual chart review. A) Fatigue Nausea and/or vomiting Anxiety Depression NLP (95% ICD (95% CI) P NLP (95% CI) ICD (95% CI) P NLP (95% CI) ICD (95% CI) P NLP (95% CI) ICD (95% CI) P CI) 0.99 (0.93- 0.59 (0.43- <0.00 0.25 (0.12- <0.00 <0.00 0.54 (0.33- Sensitivity 0.99 (0.9 – 1) 0.98 (0.88 -1) 0.3 (0.15-0.5) 0.85 (0.65-96) 0.02 1) 0.73) 1 0.42) 1 1 0.73) 0.57 (0.29- 0.9 (0.68- Specificity 0.89 (0.4-1) 0.75 (0.19-1) 0.68 0.97 (0.77-1) 0.03 0.98 (0.83-1) 0.22 0.81 (0.53-0.9) 0.96 (0.79-1) 0.06 0.82) 0.99) 0.99 (0.92- 0.86 (0.71- 0.94 (0.79- 0.79 (0.59- PPV 0.96 (0.82-1) 0.3 0.95 (0.66-1) 0.02 0.95 (0.66-1) 0.16 0.93 (0.68-1) 0.12 1) 0.95) 0.99) 0.92) 0.13 (0.03- <0.00 0.49 (0.33- <0.00 0.66 (0.48- NPV 0.89 (0.4-1) 0.007 0.94 (0.63-1) 0.34 (0.2-0.51) 0.97 (0.81-1) 0.86 (0.6-0.95) 0.04 0.35) 1 0.65) 1 0.81) <0.00 <0.00 <0.00 F1 Score 0.99 0.83 0.88 0.57 0.95 0.63 0.82 0.79 0.002 1 1 1 Itching Cramp Pain NLP (95% ICD (95% CI) P NLP (95% CI) ICD (95% CI) P NLP (95% CI) ICD (95% CI) P CI) 0.98 (0.86- 0.24 (0.09- <0.00 0.09 (0.01- <0.00 0.52 (0.37- <0.00 Sensitivity 0.98 (0.85-1) 0.99 (0.93-1) 1) 0.45) 1 0.29) 1 0.66) 1 0.89 (0.72- 0.5 (0.37- Specificity 0.96 (0.8-1) 0.98 (0.86-1) 0.68 0.98 (0.88-1) 0.18 0.5 (0-1) 1 0.98) 0.66) 0.88 (0.69- PPV 0.96 (0.8-1) 0.8 (0.54-1) 0.32 0.8 (0.16-1) 0.22 0.99 (0.93-1) 0.98 (0.87-1) NA* 0.97) 0.98 (0.85- 0.57 (0.41- <0.00 0.58 (0.43- <0.00 NPV 0.98 (0.86-1) 0.5 (0-1) 0.02 (0-0.08) NA* 1) 0.72) 1 0.72) 1 <0.00 <0.00 <0.00 F1 Score 0.97 0.56 0.91 0.28 0.99 0.68 1 1 1 *Denotes 95% confidence intervals and P values that could not be calculated due to insufficient cells in 2x2 tables. -
Cosmeceutical Products List
PROVEDA HERBALS Manufacturer of: - Soaps, Shampoos, Creams, Lotions, Gels, Hair Oil etc. Unit: - Plot no. 42, 43 Sector 2, Sidcul, IIE, BHEL, Ranipur, Haridwar, Uttrakhand, India Corporate office : A 42,Ashoka Crescent Road, DLF Phase 1, Gurugram, Haryana-122002 Website : www.provedaherbal.com, www.tbcbynature.in LIST OF COSMECEUTICALS PRODUCTS FACE WASH S.NO. PRODUCT NAME ACTIVE INGREDIENTS SKIN REJUVENATING & GLYCOLIC ACID, LACTIC ACID, VITAMIN-E, D-PANTHENOL (VITAMIN-B5), ALOEVERA 1 LIGHTENING FACE WASH WITH EXTRACT, GLYCERIN MILLIGLOBULES ANTI ACNE FACE WASH TEA TREE OIL, SALICYLIC ACID, ALOEVERA EXTRACT, VITAMIN-E, D-PANTHENOL, 2 WITH MILLIGLOBULES GLYCERIN & EXCIPIENTS NEEM ANTI-BACTERIAL FACE 3 NEEM OIL, ALOEVERA EXTRACT, TEA TREE OIL, AMLA EXTRACT WASH WITH MILLIGLOBULES ALOEVERA FACE WASH WITH 4 ALOEVERA EXTRACT, CUCUMBER EXTRACT, VITAMIN- E, D- PANTHENOL, ALLANTOIN CUCUMBER ALOEVERA FACE WASH WITH 5 ALOEVERA EXTRACT, WHEAT GERM EXTRACT, D-PANTHENOL, GLYCERIN MILLIGLOBULES SKIN LIGHTENING FACE WASH ARBUTIN, VITAMIN-B3 & E, GLYCOLIC ACID, LICORICE EXTRACT, AMLA EXTRACT, 6 WITH MILLIGLOBULES GLYCERIN, D-PANTHENOL 7 PAPAYA FACE WASH ALOEVERA EXTRACT, PAPAIN ENZYME, GLYCERIN, , D-PANTHENOL, VITAMIN-E 8 SALICYLIC ACID FACE WASH SALICYLIC ACID, TEA TREE OIL, ALOE VERA EXTRACT SHAMPOO ALOEVERA & VITAMIN-E ALOEVERA EXTRACT, VITAMIN-E, D-PANTHENOL, POLYQUATERNIUM-10, LEMON PEEL 1 SHAMPOO EXTRACT 2 MULTIVITAMIN SHAMPOO ALOEVERA, VITAMIN-E, D-PANTHENOL, POLYQUATERNIUM-10, LEMON PEEL EXTRACT PROTEIN & VITAMIN SHAMPOO SUN FLOWER SEED OIL, -
Multi Vitamin Formulations
Multi Vitamin Formulations The gender-specific men’s and women’s multivitamins and the nerve tissue supplement contain ingredients in a form that the body can easily use, in the recommended daily amounts. These ingredients promote the health of the heart, brain, muscle, bone and other parts of the body by giving them the nutrients they need to function properly. This document goes into what is in each supplement, why those ingredients are present (and in what amounts) and what that particular ingredient does in the body. All ingredients in the supplements are natural and nontoxic, and help support good health. Ingredient review for the Multi Vitamin Supplement The broad-spectrum multivitamins were formulated for men and women according to the current knowledge of daily required amounts of nutrients, and the differences in need (as in iron) between men and women. The polyphenolics, probiotics, and secondary nutrients like carnitine and ubiquinone (CoQ10) were added to help supplement the daily diet, and to help support the tissue-support supplement that it is meant to be taken along with. The focus of this section reviewing the multi-vitamin offering is to understand how these ingredients work in the body to improve overall health, and how the formula compares to the new recommended daily intake values for food and dietary supplements in the updated 21CFR section 101.9 [1]. The ingredient list and dosages for the men’s and women’s multivitamins are described in the table below. Table 1: Overview of the gender specific Multi-Vitamin Ingredient -
(12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al
USOO9498481 B2 (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao et al. (45) Date of Patent: *Nov. 22, 2016 (54) CYCLOPROPYL MODULATORS OF P2Y12 WO WO95/26325 10, 1995 RECEPTOR WO WO99/O5142 2, 1999 WO WOOO/34283 6, 2000 WO WO O1/92262 12/2001 (71) Applicant: Apharaceuticals. Inc., La WO WO O1/922.63 12/2001 olla, CA (US) WO WO 2011/O17108 2, 2011 (72) Inventors: Tadimeti Rao, San Diego, CA (US); Chengzhi Zhang, San Diego, CA (US) OTHER PUBLICATIONS Drugs of the Future 32(10), 845-853 (2007).* (73) Assignee: Auspex Pharmaceuticals, Inc., LaJolla, Tantry et al. in Expert Opin. Invest. Drugs (2007) 16(2):225-229.* CA (US) Wallentin et al. in the New England Journal of Medicine, 361 (11), 1045-1057 (2009).* (*) Notice: Subject to any disclaimer, the term of this Husted et al. in The European Heart Journal 27, 1038-1047 (2006).* patent is extended or adjusted under 35 Auspex in www.businesswire.com/news/home/20081023005201/ U.S.C. 154(b) by Od en/Auspex-Pharmaceuticals-Announces-Positive-Results-Clinical M YW- (b) by ayS. Study (published: Oct. 23, 2008).* This patent is Subject to a terminal dis- Concert In www.concertpharma. com/news/ claimer ConcertPresentsPreclinicalResultsNAMS.htm (published: Sep. 25. 2008).* Concert2 in Expert Rev. Anti Infect. Ther. 6(6), 782 (2008).* (21) Appl. No.: 14/977,056 Springthorpe et al. in Bioorganic & Medicinal Chemistry Letters 17. 6013-6018 (2007).* (22) Filed: Dec. 21, 2015 Leis et al. in Current Organic Chemistry 2, 131-144 (1998).* Angiolillo et al., Pharmacology of emerging novel platelet inhibi (65) Prior Publication Data tors, American Heart Journal, 2008, 156(2) Supp. -
Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella Alata (Anura: Bufonidae): Antiprotozoal Activity Against Trypanosoma Cruzi
molecules Article Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella alata (Anura: Bufonidae): Antiprotozoal Activity against Trypanosoma cruzi Candelario Rodriguez 1,2,3 , Roberto Ibáñez 4 , Luis Mojica 5, Michelle Ng 6, Carmenza Spadafora 6 , Armando A. Durant-Archibold 1,3,* and Marcelino Gutiérrez 1,* 1 Centro de Biodiversidad y Descubrimiento de Drogas, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Apartado 0843-01103, Panama; [email protected] 2 Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur 522510, India 3 Departamento de Bioquímica, Facultad de Ciencias Naturales, Exactas y Tecnología, Universidad de Panamá, Apartado 0824-03366, Panama 4 Smithsonian Tropical Research Institute (STRI), Balboa, Ancon P.O. Box 0843-03092, Panama; [email protected] 5 Centro Nacional de Metrología de Panamá (CENAMEP AIP), Apartado 0843-01353, Panama; [email protected] 6 Centro de Biología Celular y Molecular de Enfermedades, INDICASAT AIP, Apartado 0843-01103, Panama; [email protected] (M.N.); [email protected] (C.S.) * Correspondence: [email protected] (A.A.D.-A.); [email protected] (M.G.) Abstract: Toads in the family Bufonidae contain bufadienolides in their venom, which are charac- Citation: Rodriguez, C.; Ibáñez, R.; terized by their chemical diversity and high pharmacological potential. American trypanosomiasis Mojica, L.; Ng, M.; Spadafora, C.; is a neglected disease that affects an estimated 8 million people in tropical and subtropical coun- Durant-Archibold, A.A.; Gutiérrez, M. tries. In this research, we investigated the chemical composition and antitrypanosomal activity Bufadienolides from the Skin of toad venom from Rhinella alata collected in Panama. -
Medical Botany 6: Active Compounds, Continued- Safety, Regulations
Medical Botany 6: Active compounds, continued- safety, regulations Anthocyanins / Anthocyanins (Table 5I) O Anthocyanidins (such as malvidin, cyanidin), agrocons of anthocyanins (such as malvidin 3-O- glucoside, cyanidin 3-O-glycoside). O All carry cyanide main structure (aromatic structure). ▪ Introducing or removing the hydroxyl group (-OH) from the structure, The methylation of the structure (-OCH3, methoxyl group), etc. reactants and color materials are shaped. It is commonly found in plants (plant sap). O Flowers, leaves, fruits give their colors (purple, red, red, lilac, blue, purple, pink). O The plant's color is related to the pH of the cell extract. O Red color anthocyanins are blue, blue-purple in alkaline conditions. O Effects of many factors in color As the pH increases, the color becomes blue. the phenyl ring attached to C2; • As the OH number increases, the color becomes blue, • color increases as the methoxyl group increases. O Combination of flavonoids and anthocyanins produces blue shades. There are 6 anthocyanidins, more prevalent among ornamental-red. 3 of them are hydroxylated (delfinine, pelargonidine, cyanidin), 3 are methoxylated (malvidin, peonidin, petunidin). • Orange-colored pelargonidin related. O A hydroxyl group from cyanide contains less. • Lilac, purple, blue color is related to delphinidin. It contains a hydroxyl group more than cyanide. • Three anthocyanidines are common in methyl ether; From these; Peonidine; Cyanide, Malvidin and petunidin; Lt; / RTI & gt; derivative. O They help to pollinize animals for what they are attracted to. Anthocyanins and anthocyanidins are generally anti-inflammatory, cell and tissue protective in mammals. O Catches and removes active oxygen groups (such as O2 * -, HO *) and prevents oxidation. -
Preventive and Therapeutic Effects of Chinese Herbal Compounds Against Hepatocellular Carcinoma
molecules Review Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma Bing Hu 1,*, Hong-Mei An 2, Shuang-Shuang Wang 1, Jin-Jun Chen 3 and Ling Xu 1 1 Department of Oncology and Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; [email protected] (S.-S.W.); [email protected] (L.X.) 2 Department of Science & Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, China; [email protected] 3 Department of Plastic & Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, The Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China; [email protected] * Correspondence: [email protected]; Tel.: +86-21-64385700 Academic Editor: Derek J. McPhee Received: 16 November 2015 ; Accepted: 20 January 2016 ; Published: 27 January 2016 Abstract: Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug -
Cinobufagin Inhibits Tumor Growth by Inducing Apoptosis Through Notch Signaling Pathways in Human Cholangiocarcinoma
2469 Original Article Cinobufagin inhibits tumor growth by inducing apoptosis through Notch signaling pathways in human cholangiocarcinoma Jiajun Ren1, Shouhua Wang2, Longyang Jin2, Fei Ma3, Di Zhou2, Qiang Cai1 1Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; 2Department of General Surgery, 3Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China Contributions: (I) Conception and design: J Ren, D Zhou, Q Cai; (II) Administrative support: D Zhou, Q Cai; (III) Provision of study materials or patients: S Wang, L Jin; (IV) Collection and assembly of data: S Wang, F Ma; (V) Data analysis and interpretation: L Jin, F Ma; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Qiang Cai. Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin No. 2 Road, Shanghai 200025, China. Email: [email protected]; Di Zhou. Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. Email: [email protected]. Background: Many studies have shown that cinobufagin has antitumor effects against many cancers. The aim of this study was to assess the effects of cinobufagin on cholangiocarcinoma (CCA) cells. Methods: Colony formation assay, cell-counting kit-8 (CCK-8) assay, and tumor xenograft experiments were applied to investigate the function of cinobufagin on human CCA cells, in vitro and in vivo. Flow cytometric analysis was performed to validate the effects of cinobufagin on cell apoptosis. -
B Active™ B Active™
ÎÇÊ*/Ê >iÀ £ÉÓ»Ê*ÀÌ>LiÊ À`iÀ £{Ê*/ -ÕL i>`}Ê B Active™ 2[X]XRP[0__[XRPcX^]b UÊ-Õ««ÀÌÊi>Ì ÞÊ,iëÃiÊÌÊ-ÌÀiÃÃÊ>`Ê>Ì}Õi UÊ-Õ««ÀÌÊ >ÀL Þ`À>ÌiÊiÌ>LÃÉ*ÃÃLÞÊ,i`ÕViÊ Ã ÎÉ{»Ê À`iÀ UÊ-Õ««ÀÌÊi>Ì ÞÊ iÀÛÕÃÊ-ÞÃÌiÉ`Ài>ÊÉÕiÊÕVÌ £ä*/Ê iÊ*ÕV ià UÊ-Õ««ÀÌÊi>Ì ÞÊÀiÊ >>Vi ÌiÌÊ Ý UÊ-Õ««ÀÌÊ >À`Û>ÃVÕ>ÀÊi>Ì ÊVÕ`}ÊL`ÊViî Adbb2P]UXT[S<3 UÊ-Õ««ÀÌÊ }ÌÊ>`Êi>Ì ÞÊ` $$&($& B Active™ contains the entire spectrum of B vitamins to support a very wide range of bodily and stress-related functions. It features activated forms of vitamins B2, B6 and B12, with the addition of Benfotiamine, a patented, safe, fat-soluble, more physiologically-active form of thiamin.* BP]cP5T=<'&$& %%0eT]XSP0[STP All 360 Medicine® Formulas Meet or Exceed cGMP quality Standards 3XbRdbbX^] / iÊÜ>ÌiÀÃÕLiÊ ÊÛÌ>ÃÊ >ÛiÊÌÊLiÊ>LÃÀLi`ÊÊÌ iÊÃ>ÊÌiÃÌiÊ>`ÊÌ iÊ}ÊÌÊÌ iÊÛiÀÊÜ iÀiÊ Ì iÞÊ>ÀiÊLÌÀ>ÃvÀi`ÊÌÊÌ iÀÊ>VÌÛiÊViâÞiÊvÀðÊ>ÃÌÀÌiÃÌ>Ê>`ÉÀÊ i«>ÌVÊ«>ÀiÌÊ ÃÊiÞÊÌÊ>vviVÌÊ>LÃÀ«ÌÊ>`ÊÌ iÊ>VÌÛ>ÌÊ«ÀViÃðÊ*>Ã>Ê«ÞÀ`Ý>Êx½Ê« ë >ÌiÊ*x*®ÊiÛiÃÊÜiÀiÊ vÕ`ÊÌÊLiÊÃ}vV>ÌÞÊÜiÀÊÌ >ÊÀ>ÊÊÓÓÊÕÌÊvÊΣʫ>ÌiÌÃÊÜÌ Ê«>Ài`ÊÛiÀÊvÕV̰£ ÊVÌÛiÊVÌ>ÃÊÛÌ>ÃÊ £]Ê Ó]Ê È]Ê>`Ê £ÓÊÊÌ iÀÊ« ÞÃ}V>Þ>VÌÛiÊvÀÊ>}ÊÌ iÊi>ÃiÀÊ ÌÊ >LÃÀLÊ >`Ê ºÀi>`ÞvÀÕÃi»°Ê ÀÊ iÝ>«i]Ê Ê «>ÌiÌÃÊ ÀiViÛ}Ê «ÞÀ`ÝiÊ ]Ê ÞÊ ÎÎÊ «iÀViÌÊ Àië`i`ÊÜÌ Ê>ÊVÀi>ÃiÊÊ«>Ã>Ê*x*ÆÊ ÜiÛiÀ]ÊÌ iÊiÛiÊVÀi>Ãi`ÊÊ>ÊvÊÌ iÊ«>ÌiÌÃÊÀiViÛ}Ê *x*°£ B Active™ *iÀ >«ÃÊ Ì iÊ ÃÌÊ ÌiÀiÃÌ}Ê }Ài`iÌÊ Ê Ì ÃÊ vÀÕ>Ê ÃÊ ivÌ>iÊ -LiâÞÌ >i "« ë >Ìi®]Ê>ÊÃ>vi]Êv>ÌÃÕLiÊ>>}ÊvÊÌ >iÊÌ >ÌÊÌÊÞÊÀ>ÃiÃÊL`Ê>`ÊÌÃÃÕiÊiÛiÃÊvÊ Ì >iÊ>ÌÊi>ÃÌÊvÛiÊÌiÃÊ } iÀÊÌ >ÊÌ iÊÜ>ÌiÀÃÕLiÊÃ>Ì]ÊLÕÌÊ>ÃÊÀi>ÃÊL>Û>>LiÊ>vÌiÀÊÌ iÊÀ>Ê >`ÃÌÀ>ÌÊÕ«ÊÌÊΰÈÊÌiÃÊ}iÀÊÌ >ÊÌ >iÊÃ>̰ÓÊ -
Drug–Drug Salt Forms of Ciprofloxacin with Diflunisal and Indoprofen
CrystEngComm View Article Online COMMUNICATION View Journal | View Issue Drug–drug salt forms of ciprofloxacin with diflunisal and indoprofen† Cite this: CrystEngComm,2014,16, 7393 Partha Pratim Bag, Soumyajit Ghosh, Hamza Khan, Ramesh Devarapalli * Received 27th March 2014, and C. Malla Reddy Accepted 12th June 2014 DOI: 10.1039/c4ce00631c www.rsc.org/crystengcomm Two salt forms of a fluoroquinolone antibacterial drug, Crystal engineering approach has been effectively ciprofloxacin (CIP), with non-steroidal anti-inflammatory drugs, utilized in recent times in the synthesis of new forms particu- diflunisal (CIP/DIF) and indoprofen (CIP/INDP/H2O), were synthe- larly by exploiting supramolecular synthons. Hence the sized and characterized by PXRD, FTIR, DSC, TGA and HSM. Crystal identification of synthons that can be transferred across Creative Commons Attribution-NonCommercial 3.0 Unported Licence. structure determination allowed us to study the drug–drug different systems is important. For example, synthon trans- interactions and the piperazine-based synthon (protonated ferability in cytosine and lamivudine salts was recently dem- piperazinecarboxylate) in the two forms, which is potentially useful onstrated by Desiraju and co-workers by IR spectroscopy for the crystal engineering of new salt forms of many piperazine- studies.20a Aakeröy and co-workers successfully estab- based drugs. lished the role of synthon transferability (intermolecular amide⋯amide synthons) in the assembly and organization of Multicomponent pharmaceutical forms consisting of an bidentate acetylacetonate (acac) and acetate “paddlewheel” active pharmaceutical ingredient (API) and an inactive 20b complexes of a variety of metal(II)ions. Recently Das et al. co-former,whichisideallyagenerally recognized as safe – have reported the gelation behaviour in various diprimary This article is licensed under a 1 3 (GRAS) substance, have been well explored in recent times. -
CLINICAL PHARMACOLOGY and BIOPHARMACEUTICS REVIEW(S) NDA 22561 Clinical Pharmacology Amendment Memo
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 022561Orig1s000 CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW(S) NDA 22561 Clinical Pharmacology Amendment Memo NDA Number: 22561 Submission Date: May 30, 2018 Submission Type: Standard Brand Name: Mavenclad Generic Name: Cladribine Dosage Form and Strength: Tablets, 10 mg Route of Administration: Oral Proposed Indication: Treatment of Relapsing forms of Multiple Sclerosis (RMS) Applicant: EMD Serono, Inc. OCP Review Team: Hristina Dimova, Ph.D., Angela Men, M.D., Ph.D., Mehul Mehta, Ph.D. This review is an amendment of the NDA 22561 review for Mavenclad, (cladribine in DARRTS on March 13, 2019) focusing on a new proposed Post-marketing Requirement (PMR). Background of Metabolism and in-vitro studies results: Cladribine is not a substrate of cytochrome P450 enzymes and does not show significant potential to act as inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Cladribine has no clinically meaningful inductive effect on CYP1A2, CYP2B6 and CYP3A4 enzymes. Transporter Systems: Cladribine is a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), equilibrative nucleoside transporter 1 (ENT1) and concentrative nucleoside transporter 3 (CNT3). New PMR: Conduct a clinical drug-drug interaction (DDI) study to evaluate the effect of cladribine on the pharmacokinetics (PK) of oral contraceptives. Include an evaluation of the effect on the components ethinyl estradiol (EE) and norelgestromin (NGMN). Rationale: No in vivo DDI study has been conducted to evaluate the effect of cladribine on systemically acting hormonal contraceptives. Currently it is unknown whether cladribine may reduce the effectiveness of hormonal contraceptives. Considering the in vitro study results described in Section 3.3.3. -
Hazard Assessment of Glycyrrhizic Acid from Liquorice
VKM Report 2018: 09 Hazard assessment of glycyrrhizic acid from liquorice Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food and Environment Report from the Norwegian Scientific Committee for Food and Environment (VKM) 2018: 09 Hazard assessment of glycyrrhizic acid from liquorice Opinion of Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food and Environment 08.05.2018 ISBN: 978-82-8259-306-9 ISSN: 2535-4019 Norwegian Scientific Committee for Food and Environment (VKM) Po 4404 Nydalen N – 0403 Oslo Norway Phone: +47 21 62 28 00 Email: [email protected] vkm.no vkm.no/English Cover photo: ColourBox Suggested citation: VKM, Inger-Lise Steffensen, Gro Haarklou Mathisen, Ellen Bruzell, Berit Brunstad Granum, Jens Rohloff, Ragna Bogen Hetland (2018) Hazard assessment of glycyrrhizic acid from liquorice. Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics. ISBN: 978-82-8259-306-9. Norwegian Scientific Committee for Food and Environment (VKM), Oslo, Norway. VKM Report 2018: 09 Hazard assessment of glycyrrhizic acid from liquorice Preparation of the opinion The Norwegian Scientific Committee for Food and Environment (Vitenskapskomiteen for mat og miljø, VKM) appointed a project group to answer the request from the Norwegian Food Safety Authority. The project group consisted of two VKM members of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics and a project leader from the VKM secretariat.