DOCSLIB.ORG

WO 2017/033032 Al 2 March 2017 (02.03.2017) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2017/033032 Al 2 March 2017 (02.03.2017) 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 2017/033032 Al 2 March 2017 (02.03.2017) P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 9/14 (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/GB20 16/052680 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, 30 August 2016 (30.08.2016) 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, 15 15310.9 27 August 2015 (27.08.2015) GB TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: JAGOTEC AG [CH/CH]; Eptingerstrasse 61, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, CH-4132 Muttenz (CH). LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, (72) Inventors: MUELLER-WALZ, Rudi; Eptingerstrasse 61, GW, KM, ML, MR, NE, SN, TD, TG). 4132 Muttenz (CH). FRD3EZ, Morgan; Eptingerstrasse 61, 4132 Muttenz (CH). BALAXI, Maria; Eptingerstrasse Published: 61, 4132 Muttenz (CH). — with international search report (Art. 21(3)) (74) Agent: BERESFORD CRUMP LLP; 16 High Holborn, — before the expiration of the time limit for amending the London Greater London WC1V 6BX (GB). claims and to be republished in the event of receipt of (81) Designated States (unless otherwise indicated, for every amendments (Rule 48.2(h)) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, o o o (54) Title: PHARMACEUTICAL COMPOSITION FOR INHALATION (57) Abstract: The present invention provides a pharmaceutical composition for inhalation comprising a first active agent and a second active agent, wherein the aerodynamic particle size distribution of the first and second active agents relative to their delivered doses is substantially the same. PHARMACEUTICAL COMPOSITION FOR INHALATION The present invention relates to a pharmaceutical composition for inhalation comprising a first active agent and a second active agent, wherein the aerodynamic particle size distribution of the first and second active agents relative to their delivered doses is substantially the same. Drugs for the treatment of respiratory diseases and disorders, such as beta-2 agonists, corticosteroids, muscarinic antagonists and phosphodiesterase inhibitors are frequently administered directly to the lungs via inhalation. The inhalation route may also be used for the delivery of systemically acting drugs. Administration via inhalation can increase the therapeutic index, reduce side effects of the drugs compared to administration by other routes (such as orally or intravenously), can result in a rapid speed of onset of the drugs, and in improved patient compliance. Administration by inhalation may be in the form of either dry powders or aerosol formulations, which are inhaled by the patient either through use of an inhalation device or nebuliser. While single active agents may be employed to treat a specific disease or disorder, the use of combinations of drugs is often advantageous. For example low-dose therapy using one drug may not be sufficient to control asthma symptoms, but adding treatment with another drug having a different mechanism of action may significantly improve symptoms compared with simply increasing a patient's dose of a single drug, while also reducing side effects. A combination of drugs may also have a synergistic effect, leading to enhanced patient treatment. Alternatively, the two drugs may act to treat two different symptoms; for example one drug may treat the airway constriction while the other may reduce or prevent inflammation of the airways. Formulating two active agents in a single formulation for administration from a single inhalation device is particularly advantageous for improving patient compliance. In order that a medicinal formulation is suitable for use with an inhalation device, the particle size of the deployed formulation must be small enough that it can be inhaled into the lungs of the users. Therefore, the particles of the formulation need to be in the micrometer size range, i.e. having a mean aerodynamic particle diameter (measured as Mass Median Aerodynamic Diameter (MMAD)) of about 1 to Ι Οµ , in order to be capable of penetrating into the lungs and exerting its intended pharmacological effect. The particle size of the active agents should not be larger than 1Οµηι and preferably not larger than 5µ η. Various methods may be used to form such fine particles for inhalation which are known to the skilled person. The most widely used method of producing particles of a drug compound in the micrometer size range is a particle reduction technique called micronisation, using an air jet mill. Jet milling is a highly effective technology for reducing the particle size of drugs where the size of the particles is relevant to the effective delivery. Air jet mills grind materials by using a high speed jet of compressed air or inert gas which accelerates particles fed into the grinding chamber. Particle reduction is achieved by the impact of particles colliding into each other at high speed and reducing themselves by attrition and collision. Air jet mills are usually designed to output particles below a certain size; the compressed air or gas jet exits the mill through an outlet at the center of the grinding chamber and draws the micronised particles with it. Larger, i.e. oversized particles are held in the grinding chamber by centrifugal force and continue the milling process until the desired micrometer size is achieved, allowing them to escape the grinding chamber. Particles leaving the mill can eventually be separated from the gas stream by c3/clonic separation. Due to this design, a narrow particle size distribution of the resulting product can be achieved. The resulting particle size distribution of micronised drug compound depends on several parameters, such as the diameter of the air jet mill, the grinding gas pressure, the feeding gas pressure and the feeding rate. Furthermore, drug compound specific characteristics are also important for the result and need to be considered, such as the starting particle size range of the un-micronised compound, hardness, friability, temperature sensitivity (softening at higher temperature), or polymorph stability. Oxygen or moisture sensitivity of the drug compound may also demand the use of inert gas as a feeding and grinding media. The above described compound specific parameters usually require that micronisation trials are performed to establish the suitable set of process parameters with control ranges needed to yield micronised particles of the requested target particle size. The skilled person would also understand that each specific drug compound may require its defined individual set of process parameters. In the case of a combination drug product, the different microfine drug powders as constituents of the combination drug product are therefore normally manufactured and micronised separately, and only combined at a later stage of preparation of the finished drug product. However, separate preparation of the two active agents may result in differing behaviour in the finished drug product and therefore different delivery or deposition at different locations in the lungs may well occur. It would therefore be advantageous to formulate a pharmaceutical combination product in which the two active agents deliver to and deposit at the same site in the lungs. According to a first aspect of the present invention there is provided a pharmaceutical composition for inhalation comprising a first active agent and a second active agent, wherein the aerodynamic particle size distribution (APSD) of the first and second active agents relative to their delivered doses is substantially the same. The aerodynamic particle size distribution relative to the delivered dose is preferably substantially the same within ± 25% on each impactor stage, preferably within ± 20% on each impactor stage, more preferably within ± 15% on each impactor stage, more preferably within ±10% on each impactor stage. It has been found that by ensuring that the first and active agents have an APSD relative to their delivered doses that is substantially the same, co-deposition of the active agents occurs. This is particularly useful when co-deposition of both drugs in the same target area is required to exert a synergistic pharmacological effect, for allowing targeted treatment of a small area of infected lung or for targeting a specific region of the lungs (for example, the central airways to treat asthma, or the alveoli for a drug intended for systemic administration). It is well established that cascade impactors may be used as an instrument to determine the aerodynamic particle size distribution of airborne drug particles delivered from inhaled formulations. Cascade impactors separate the drug particles contained in the formulation into fractions on the basis of differences in inertia, which is a function of particle density, shape, and velocity. Two types of cascade impactors widely used in the pharmaceutical development of inhaled formulations are the Andersen Cascade Impactor (ACI) and the Next Generation Impactor (NGI).
Load more

Recommended publications
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Piclamilast Item No. 29170 CAS Registry No.: 144035-83-6 Formal Name: 3-(cyclopentyloxy)-N-(3,5-dichloro- 4-pyridinyl)-4-methoxy-benzamide O Synonyms: RP 73401, RPR 73401 Cl H MF: C18H18Cl2N2O3 FW: 381.3 N O Purity: ≥98% O Supplied as: A solid N Storage: -20°C Cl Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Piclamilast is supplied as a solid. A stock solution may be made by dissolving the piclamilast in the solvent of choice, which should be purged with an inert gas. Piclamilast is soluble in organic solvents such as ethanol and DMSO. The solubility of piclamilast in ethanol is approximately 20 mM and approximately 100 mM in DMSO. Description 1 Piclamilast is a phosphodiesterase 4 (PDE4) inhibitor (IC50 = 0.31 nM). It is selective for PDE4 over PDE1, 2,3 PDE2, PDE3, PDE5, and PDE7A in cell-free assays (IC50s = >100, 40, >100, 14, and >10 μM, respectively). Piclamilast inhibits superoxide production by guinea pig eosinophils and histamine-induced contraction 1,4 in isolated guinea pig trachea (IC50s = 24 and 2 nM, respectively). It inhibits eosinophil, neutrophil, lymphocyte, and TNF-α accumulation in bronchoalveolar lavage fluid (BALF) from ovalbumin-sensitized 5 rats (ED50s = 23.8, 14.1, 19.5, and 14.4 μmol/kg, respectively). Piclamilast also inhibits ovalbumin-induced 2 bronchoconstriction in a guinea pig model of asthma (ED50 = 0.033 mg/kg). References 1. Ashton, M.J., Cook, D.C., Fenton, G., et al. Selective type IV phosphodiesterase inhibitors as antiasthmatic agents.
    [Show full text]
  • Comparison of Norepinephrine and Cafedrine/Theodrenaline Regimens for Maintaining Maternal Blood Pressure During
    IBIMA Publishing Obstetrics & Gynecology: An International Journal http://www.ibimapublishing.com/journals/GYNE/gyne.html Vol. 2015 (2015), Article ID 714966, 12 pages DOI: 10.5171/2015.714966 Research Article Comparison of Norepinephrine and Cafedrine/Theodrenaline Regimens for Maintaining Maternal Blood Pressure during Spinal Anaesthesia for Caesarean Section Hoyme, M.1, Scheungraber, C.2, Reinhart, K.3 and Schummer, W.3 1Department of Internal Medicine I (Cardiology, Angiology, Pneumology) Friedrich Schiller University, Jena, Germany 2Departments of Obstetrics and Gynecology, Friedrich Schiller University, Jena, Germany 3Clinic of Anaesthesiology and Intensive Care Medicine, Friedrich Schiller University, Jena, Germany Correspondence should be addressed to: Schummer, W.; [email protected] Received date: 9 January 2014; Accepted date: 4 April 2014; Published date: 26 August 2015 Academic Editor: Dan Benhamou Copyright © 2015. Hoyme, M., Scheungraber, C., Reinhart, K. and Schummer, W. Distributed under Creative Commons CC-BY 4.0 Abstract Common phenomena of spinal anaesthesia for caesarean sections are hypotension and cardiovascular depression, both of which require immediate action. Akrinor® (theodrenaline and cafedrine), a sympathomimetic agent commonly used in Germany for such cases, was phased out with little notice at the end of 2005. Phenylephrine was not and is not an approved drug. Norepinephrine became the first-line drug. The outcome in neonates delivered by elective caesarean section under spinal anaesthesia was studied. At our university hospital, all elective caesarean sections under spinal anaesthesia from 2005 and 2006 were analysed regarding hypotension and the vasopressor administered. If maternal arterial pressure decreased by more than 20% of baseline, patients in 2005 received Akrinor®; patients in 2006 received norepinephrine.
    [Show full text]
  • Hypotension After Spinal Anesthesia for Cesarean
    REVIEW CURRENT OPINION Hypotension after spinal anesthesia for cesarean section: how to approach the iatrogenic sympathectomy Christina Massotha, Lisa To¨pelb, and Manuel Wenkb Purpose of review Hypotension during cesarean section remains a frequent complication of spinal anesthesia and is associated with adverse maternal and fetal events. Recent findings Despite ongoing research, no single measure for sufficient treatment of spinal-induced hypotension was 05/25/2020 on BhDMf5ePHKbH4TTImqenVDezntqwKeJGjCYTUOBBz0EyVSh+WquM7uJo3U//pWTO by http://journals.lww.com/co-anesthesiology from Downloaded Downloaded identified so far. Current literature discusses the efficacy of low-dose spinal anesthesia, timing and solutions for adequate fluid therapy and various vasopressor regimens. Present guidelines favor the use of from phenylephrine over ephedrine because of decreased umbilical cord pH values, while norepinephrine is http://journals.lww.com/co-anesthesiology discussed as a probable superior alternative with regard to maternal bradycardia, although supporting data is limited. Alternative pharmacological approaches, such as 5HT3-receptor antagonists and physical methods may be taken into consideration to further improve hemodynamic stability. Summary Current evidence favors a combined approach of low-dose spinal anesthesia, adequate fluid therapy and vasopressor support to address maternal spinal-induced hypotension. As none of the available vasopressors by is associated with relevantly impaired maternal and fetal outcomes, none of them should
    [Show full text]
  • [3H]-Piclamilast and [3H]-Rolipram
    JPET Fast Forward. Published on January 24, 2003 as DOI: 10.1124/jpet.102.047407 JPET FastThis articleForward. has not Published been copyedited on and January formatted. 24,The final2003 version as DOI:10.1124/jpet.102.047407 may differ from this version. Inhibitor Binding to Type 4 Phosphodiesterase (PDE4) Assessed Using [3H]-Piclamilast and [3H]-Rolipram Yu Zhao, Han-Ting Zhang, and James M. O’Donnell Department of Pharmacology University of Tennessee Health Science Center Downloaded from Memphis, Tennessee jpet.aspetjournals.org at ASPET Journals on September 27, 2021 1 Copyright 2003 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on January 24, 2003 as DOI: 10.1124/jpet.102.047407 This article has not been copyedited and formatted. The final version may differ from this version. Running title: Inhibitor binding to PDE4 Correspondence should be addressed to: James M. O’Donnell, Ph.D. Department of Pharmacology University of Tennessee Health Science Center 874 Union Avenue Downloaded from Memphis, TN 38163 jpet.aspetjournals.org Phone: 901-448-3621 Fax: 901-448-3849 Email: [email protected] at ASPET Journals on September 27, 2021 Number of text page: 31 Number of tables: 3 Number of figures: 7 Number of references: 50 Number of words: Abstract (241); Introduction (716); Discussion (1544) Abbreviations: EHNA, erythro-9-(2-hydroxy-3-nonyl)adenine; HARBS, high-affinity rolipram binding site; LARBS, low-affinity rolipram binding site; IBMX, 3-isobutyl-1- methylxanthine; PDE, phosphodiesterase Section: Neuropharmacology 2 JPET Fast Forward. Published on January 24, 2003 as DOI: 10.1124/jpet.102.047407 This article has not been copyedited and formatted.
    [Show full text]
  • Chronic Obstructive Lung Disease
    Chronic Obstructive Lung Disease Amita Vasoya, DO FACOI FCCP FAASM Christiana Care Pulmonary Associates Clinical Assistant Professor of Medicine Sidney Kimmel Medical College of Thomas Jefferson University Rowan University School of Osteopathic Medicine ACOI Board Review 2019 Disclosures No Disclosures Obstructive Lung Diseases COPD Chronic ◦ Chronic Bronchitis Bronchitis Emphysema ◦ Emphysema Asthma Other ◦ Bronchiectasis Asthma ◦ Bronchiolitis ◦ Cystic Fibrosis ◦ Alpha 1 anti-trypsin deficiency Inter-relationship: Inflammation and Bronchial Hyperreactivity ATS GOLD CHEST 2002; 121: 121S-126S COPD THIRD leading cause of death worldwide It is the only leading cause of death whose prevalence is increasing! http://www.who.int/mediacentre/factsheets COPD Risk Factors Cigarette smoking Occupational exposures ◦ Silica, formaldehyde, toluene, nickel, cadmium, cotton, dust, etc Air pollution Biomass fuel Hyperresponsive airway Asthma Genetic factors Pathogenesis of COPD ATS Pulmonary Board Review 2015 Inflammatory Mediators: COPD ATS Pulmonary Board Review 2015 INFLAMMATION Small Airway Disease Parenchyma destruction Airway inflammation Loss of alveolar attachments Airway remodeling Decreased elastic recoil AIRFLOW LIMITATION ATS Pulmonary Board Review 2015 COPD Phenotypes Non-exacerbator Exacerbator with emphysema Exacerbator with chronic bronchitis Frequent exacerbator Alpha 1 Antitrypsin deficiency ACOS BCOS www.eclipse-copd.com, Lange P. Int J COPD 2016. 11: 3-12 Hurst JR. NEJM 2010. 363: 1128-38 Morphologic Types of
    [Show full text]
  • ED Analogues Analysis
    UPLC-MS/MS for the Screening, Confirmation and Quantification of 32 Drugs illegally added to Herbal/Dietary Supplements for the Enhancement of Male Sexual Performance 1Salman Azimi*, 2Nayan Mistry and 2Michelle Wood 1Drug Quality Control Laboratory, Pharmacy & Drug Control Dept., Supreme Council of Health, PO Box 1919, Doha - Qatar. 2 Figure-5: Photographs of six positive samples. Forty-three suspected Waters Corporation, Atlas Park, Wythenshawe, Manchester, M22 5PP, UK. samples were analyzed in this study; 18 were found to be adulterated with ED drugs. ABSTRACT RESULTS & DISCUSSION The adulteration of herbal/dietary supplements with erectile dysfunction (ED) drugs and their analogues is reported For the purpose of screening , a spectral library for known ED drugs and analogues was prepared. Owing to recent reports Table 2: List of 32 compounds with retention times, and optimised MRM transitions parameters. Table-3: Summary of results for eight adulterated herbal/dietary samples. The screening results, including spectral match worldwide and is an increasing problem[1]. The sale of so-called 100%, ‘all-natural’ products has become a highly of increased availability of ‘all-in-one’/ ‘combination’ herbal products[2], we also added the naturally-occurring substances factors, RT data and final screening status ( = positive or - = negative) are presented, in addition to the quantitative data Retention Precursor Cone Quantifier Qualifier %CV (n=4) from the subsequent confirmatory analysis. profitable business for online pharmacies, however these products can pose a serious threat to consumers owing to the Icariin and yohimbine, the synthetic, dapoxetine (used for premature ejaculation) and testosterone. The library was CE CE Dwell LOQ undisclosed presence of approved/prescription drugs or the unknown safety and toxicity profile of unapproved ED drugs.
    [Show full text]
  • PDE4-Inhibitors: a Novel, Targeted Therapy for Obstructive Airways Disease Zuzana Diamant, Domenico Spina
    PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease Zuzana Diamant, Domenico Spina To cite this version: Zuzana Diamant, Domenico Spina. PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease. Pulmonary Pharmacology & Therapeutics, 2011, 24 (4), pp.353. 10.1016/j.pupt.2010.12.011. hal-00753954 HAL Id: hal-00753954 https://hal.archives-ouvertes.fr/hal-00753954 Submitted on 20 Nov 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Accepted Manuscript Title: PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease Authors: Zuzana Diamant, Domenico Spina PII: S1094-5539(11)00006-X DOI: 10.1016/j.pupt.2010.12.011 Reference: YPUPT 1071 To appear in: Pulmonary Pharmacology & Therapeutics Received Date: 2 October 2010 Revised Date: 5 December 2010 Accepted Date: 24 December 2010 Please cite this article as: Diamant Z, Spina D. PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease, Pulmonary Pharmacology & Therapeutics (2011), doi: 10.1016/j.pupt.2010.12.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript.
    [Show full text]
  • Chapter Introduction
    VU Research Portal Trypanosoma brucei phosphodiesterase B1 as a drug target for Human African Trypanosomiasis Jansen, C.J.W. 2015 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Jansen, C. J. W. (2015). Trypanosoma brucei phosphodiesterase B1 as a drug target for Human African Trypanosomiasis. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 05. Oct. 2021 An introduction into phosphodiesterases and their potential role as drug targets for neglected diseases Chapter 1 4 CHAPTER 1 1.1 Human African Trypanosomiasis Human African Trypanomiasis (HAT), also known as African sleeping sickness, is a deadly infectious disease caused by the kinetoplastid Trypanosoma
    [Show full text]
  • Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy Using Machine Learning
    Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy using Machine Learning Kate Wang et al. Supplemental Table S1. Drugs selected by Pharmacophore-based, ML-based and DL- based search in the FDA-approved drugs database Pharmacophore WEKA TF 1-Palmitoyl-2-oleoyl-sn-glycero-3- 5-O-phosphono-alpha-D- (phospho-rac-(1-glycerol)) ribofuranosyl diphosphate Acarbose Amikacin Acetylcarnitine Acetarsol Arbutamine Acetylcholine Adenosine Aldehydo-N-Acetyl-D- Benserazide Acyclovir Glucosamine Bisoprolol Adefovir dipivoxil Alendronic acid Brivudine Alfentanil Alginic acid Cefamandole Alitretinoin alpha-Arbutin Cefdinir Azithromycin Amikacin Cefixime Balsalazide Amiloride Cefonicid Bethanechol Arbutin Ceforanide Bicalutamide Ascorbic acid calcium salt Cefotetan Calcium glubionate Auranofin Ceftibuten Cangrelor Azacitidine Ceftolozane Capecitabine Benserazide Cerivastatin Carbamoylcholine Besifloxacin Chlortetracycline Carisoprodol beta-L-fructofuranose Cilastatin Chlorobutanol Bictegravir Citicoline Cidofovir Bismuth subgallate Cladribine Clodronic acid Bleomycin Clarithromycin Colistimethate Bortezomib Clindamycin Cyclandelate Bromotheophylline Clofarabine Dexpanthenol Calcium threonate Cromoglicic acid Edoxudine Capecitabine Demeclocycline Elbasvir Capreomycin Diaminopropanol tetraacetic acid Erdosteine Carbidopa Diazolidinylurea Ethchlorvynol Carbocisteine Dibekacin Ethinamate Carboplatin Dinoprostone Famotidine Cefotetan Dipyridamole Fidaxomicin Chlormerodrin Doripenem Flavin adenine dinucleotide
    [Show full text]
  • 2251 Adulteration of Dietary Supplements with Drugs
    BRIEFING 2251 Adulteration of Dietary Supplements with Drugs and Drug Analogs. This new general chapter provides tools for detection of dietary supplement adulteration with ⟨extraneously⟩ added synthetic compounds. The illegal addition of synthetic substances to products marketed as dietary supplements constitutes a significant threat to consumer health, considering that these products, administered without medical supervision, may contain toxic constituents or substances whose safety has never been examined, and whose interaction with medications may be unpredictable or lethal. The proposed chapter suggests multiple methods for detection of adulteration. It is advisable to use several screening techniques to maximize the potential for adulteration detection, because no single methodology is universally applicable. Presently, the chapter targets supplements adulterated with phosphodiesterase type 5 inhibitors; subsequent revisions will include methodologies specific to analysis of adulterated weight loss and sports performance enhancement products. It is anticipated that this chapter will be updated regularly. (GCCA: A. Bzhelyansky.) Correspondence Number—C144928 Add the following: ▪ 2251 ADULTERATION OF DIETARY SUPPLEMENTS WITH DRUGS AND DRUG ANALOGS ⟨ ⟩ INTRODUCTION The illegal addition of undeclared synthetic compounds to products marketed as dietary supplements1 (DS) is a serious problem. This fraud is practiced to impart therapeutic effects that cannot be achieved by the supplement constituents alone. Increasingly, synthetic intermediates and structural analogs of the pharmaceuticals and drugs that have been discontinued or withdrawn from the market due to unsatisfactory safety profiles are being used as adulterants. Multiple adulterating compounds may be added to a single DS, frequently in erratic amounts. The proposed test methodologies facilitate screening of DS for synthetic adulterants. No individual technique is capable of addressing all potential analytes; thus, a combination of orthogonal approaches adds certainty to the analytical outcome.
    [Show full text]
  • Wo 2010/075090 A2
    (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 1 July 2010 (01.07.2010) WO 2010/075090 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 409/14 (2006.01) A61K 31/7028 (2006.01) kind of national protection available): AE, AG, AL, AM, C07D 409/12 (2006.01) A61P 11/06 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2009/068073 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 15 December 2009 (15.12.2009) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (26) Publication Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/122,478 15 December 2008 (15.12.2008) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): AUS- ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, PEX PHARMACEUTICALS, INC.
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]