DOCSLIB.ORG

Aluminum and Phthalates in Calcium Gluconate: Contribution from Glass and Plastic Packaging

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Aluminum and Phthalates in Calcium Gluconate: Contribution from Glass and Plastic Packaging University of Kentucky UKnowledge Pharmaceutical Sciences Faculty Publications Pharmaceutical Sciences 1-2017 Aluminum and Phthalates in Calcium Gluconate: Contribution from Glass and Plastic Packaging Robert A. Yokel University of Kentucky, [email protected] Jason M. Unrine University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Follow this and additional works at: https://uknowledge.uky.edu/ps_facpub Part of the Pharmacy and Pharmaceutical Sciences Commons, and the Toxicology Commons Aluminum and Phthalates in Calcium Gluconate: Contribution from Glass and Plastic Packaging Digital Object Identifier (DOI) https://doi.org/10.1097/MPG.0000000000001243 Notes/Citation Information Published in Journal of Pediatric Gastroenterology & Nutrition, v. 64, no. 1, p. 109-114. Copyright © 2017 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology. The document available for download is the authors' post-peer-review final draft of the article. It is made available under the terms of the Creative Commons Attribution-NonCommercial (CC BY-NC) license. This article is available at UKnowledge: https://uknowledge.uky.edu/ps_facpub/69 Title Page Aluminum and phthalates in calcium gluconate; contribution from glass and plastic packaging Robert A. Yokel, PhD 1,2*, Jason M. Unrine, PhD 2,3 1Pharmaceutical Sciences, 2Graduate Center for Toxicology, 3Plant and Soil Sciences, University of Kentucky, Lexington, KY *Corresponding author: Robert A. Yokel, Ph.D. Department of Pharmaceutical Sciences 335 Biopharmaceutical Complex (College of Pharmacy) Building College of Pharmacy University of Kentucky Academic Medical Center Lexington, KY, 40536-0596 phone: 859-257-4855 fax: 859-257-7564 e-mail: [email protected] Word count of manuscript body: ~ 2230 Number of figures: 2 Number of Tables: 2 Conflict of interest: Robert Yokel is a founder and President of ALKYMOS, Inc. ALKYMOS was developing a device to remove aluminum from calcium gluconate solution. Given the release of Calcium Gluconate Injection USP in plastic packaging in the US, as cited in this report, which has a concentration of aluminum in the range that was achievable with the ALKYMOS device filtered calcium gluconate from glass-packaged product, ALKYMOS has suspended development of its device. Robert Yokel has no further conflict of interest related to this report. Jason Unrine has no conflict of interest related to this report. Revised Manuscript - Clean Abstract: Introduction: Aluminum contamination of parenteral nutrition solutions has been documented for three decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration the past three decades has averaged ~ 4000 µg/L, compared to < 200 µg/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity. Methods: Aluminum was quantified in samples collected periodically over more than two years from three calcium gluconate sources used to prepare parenteral nutrition solutions; two packaged in glass (from France and the US) and one in plastic (from Germany); in a recently released plastic- packaged solution (from the US); and in the two glass containers. Phthalate concentration was determined in selected samples of each product and leachate of the plastic containers. Results: The initial aluminum concentration was ~ 5000 µg/L in the two glass-packaged products and ~ 20 µg/L in the plastic-packaged product, and increased ~ 30, 50 and 100% over 2 years, respectively. The aluminum concentration in a recently released Calcium Gluconate Injection USP was ~ 320 µg/L. Phthalates were not detected in any calcium gluconate solutions or leachates. Conclusion: Plastic packaging greatly reduces the contribution of aluminum to parenteral nutrition solutions from calcium gluconate compared to the glass-packaged product. 1 What is known: Aluminum is a contaminant of parenteral nutrition solutions. Aluminum can cause neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. Glass-packaged calcium gluconate is the primary aluminum source of parenteral nutrition solutions. What is new: As received glass-packaged calcium gluconate provides aluminum in excess of the FDA’s recognized level that results in aluminum accumulation associated with central nervous system and bone toxicity. Aluminum in calcium gluconate increases over two years of storage. Calcium gluconate packaged in the tested plastic containers does not provide aluminum in excess of the FDA level or measurable phthalates (plasticizers with potential to cause male reproductive system disruption and neurotoxicity). 2 Introduction: Aluminum contamination of parenteral nutrition solutions has been a documented problem for three decades (1-4), which can result in elevated blood aluminum (5), increased body burden (5, 6), increased bone aluminum (7), neurotoxicity (8), reduced bone mass and mineral content (6, 9), and perhaps hepatotoxicity (10, 11). This led to a US FDA labeling requirement addressing this issue, which concludes that “patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 [micro]g/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity” (12). The primary source of aluminum in parenteral nutrition solutions is calcium gluconate, reported to contribute up to 88% vs. ~ 4% from phosphates (13), 88.7% (14), 78% to home parenteral nutrition solutions (15), 81 vs. 9% from sodium phosphate (16), ~ 50% (17), 80% to 98% (18), 80 ± 22% (19), the main source of aluminum (20), and highest amounts were provided by dextrose and calcium gluconate (21). The raw material was identified as one, but not the sole source (22). The aluminum primarily comes from glass packaging (23-26). Aluminum is added to the glass of containers of parenteral solutions to improve resistance to chemical attack and thermal shock (27). Table 1 shows the reported concentrations of aluminum in calcium gluconate used to prepare parenteral nutrition solutions. Most of these values indicate that the aluminum concentration in this product, when packaged in glass, has averaged ~ 4000 µg/L, and has not decreased over the past three decades. Excluding three high values there has 3 been a non-significant increase in the aluminum concentration in calcium gluconate packaged in glass over the past three decades (Figure 1). The average daily administration of aluminum to premature and term infants has been found to be 15 to 25 µg/kg (5, 39, 43, 44), or three to five times the upper boundary of the US FDA guideline, and even higher in Argentina (21). In the United States, until mid- 2015, Calcium Gluconate Injection USP had only been available in glass packaging. Pharmacists had few opportunities to minimize aluminum administration in parenteral nutrition solutions, limited to using the most recently obtained product, based on the assumption that the aluminum concentration increases over storage time in the glass container (4, 45), as shown by one study cited in Table 1 (40). A few reports have shown much less aluminum in calcium gluconate packaged in plastic containers (Table 1) (37, 40). There have been encouragements to abandon glass packaged calcium gluconate in favor of plastic packaging (20, 40). A concern about plastic packaging is the possibility that the product contains leached plasticizers, particularly phthalates such as DEHP (bis(2-ethylhexyl) phthalate, aka: di-2-ethylhexyl phthalate, diethylhexyl phthalate). Phthalates have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity. Infants are the most susceptible population (46, 47). Plasticizers might present a hazard not inherent to glass containers, although the rubber stopper of glass vials could be a source. 4 The present study was conducted to quantify the aluminum concentration over the shelf life of representative calcium gluconate solutions used to prepare parenteral nutrition solutions, and to determine the initial aluminum concentration and the rate and extent of aluminum concentration increase over storage time. The concentration of phthalates, including DEHP, was determined to ascertain if calcium gluconate provided a risk from exposure to these plasticizers. 5 Methods: Multiple containers of calcium gluconate solutions used in the preparation of parenteral nutrition solutions were obtained from three sources in July, 2013; APP Pharmaceuticals, LLC, US, packaged in glass; C.D.M. Lavoisier, France, packaged in glass; and B. Braun, Germany, packaged in plastic. A single vial packaged in glass was obtained from Fresenius Kabi, LLC, US, in May, 2015. Approximately half of the 10 mL calcium gluconate contents of individual containers from APP Pharmaceuticals and B. Braun was clean poured into duplicate seven mL perfluoroalkoxy alkanes (PFA) vials at ~ 1.5 month intervals from July 19, 2013 through August 25, 2015. The interval between sample transfers of the Lavoisier product was ~ every 3 months after the first
Load more

Recommended publications
  • Report Name:Ukraine's Mrls for Veterinary Drugs
    Voluntary Report – Voluntary - Public Distribution Date: November 05,2020 Report Number: UP2020-0051 Report Name: Ukraine's MRLs for Veterinary Drugs Country: Ukraine Post: Kyiv Report Category: FAIRS Subject Report Prepared By: Oleksandr Tarassevych Approved By: Robin Gray Report Highlights: Ukraine adopted several maximum residue levels (MRLs) for veterinary drugs, coccidiostats and histomonostats in food products of animal origin. Ukraine also adopted a list of drugs residues that are not allowed in food products. THIS REPORT CONTAINS ASSESSMENTS OF COMMODITY AND TRADE ISSUES MADE BY USDA STAFF AND NOT NECESSARILY STATEMENTS OF OFFICIAL U.S. GOVERNMENT POLICY The Office of Agricultural Affairs of USDA/Foreign Agricultural Service in Kyiv, Ukraine prepared this report for U.S. exporters of domestic food and agricultural products. While every possible care was taken in the preparation of this report, information provided may not be completely accurate either because policies have changed since the time this report was written, or because clear and consistent information about these policies was not available. It is highly recommended U.S. exporters verify the full set of import requirements with their foreign customers, who are normally best equipped to research such matters with local authorities, before any goods are shipped. This FAIRS Subject Report accompanies other reports on Maximum, Residue Limits established by Ukraine in 2020. Related reports could be found under the following links: 1.) Ukraine's MRLs for Microbiological Contaminants_Kyiv_Ukraine_04-27-2020 2.) Ukraine's MRLs for Certain Contaminants_Kyiv_Ukraine_03-06-2020 Food Products of animal origin and/or ingredients of animal origin are not permitted in the Ukrainian market if they contain certain veterinary drugs residues in excess of the maximum residue levels established in Tables 1 and 2.
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) 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. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Australian Statistics on Medicines 1997 Commonwealth Department of Health and Family Services
    Australian Statistics on Medicines 1997 Commonwealth Department of Health and Family Services Australian Statistics on Medicines 1997 i © Commonwealth of Australia 1998 ISBN 0 642 36772 8 This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be repoduced by any process without written permission from AusInfo. Requests and enquiries concerning reproduction and rights should be directed to the Manager, Legislative Services, AusInfo, GPO Box 1920, Canberra, ACT 2601. Publication approval number 2446 ii FOREWORD The Australian Statistics on Medicines (ASM) is an annual publication produced by the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee. Comprehensive drug utilisation data are required for a number of purposes including pharmacosurveillance and the targeting and evaluation of quality use of medicines initiatives. It is also needed by regulatory and financing authorities and by the Pharmaceutical Industry. A major aim of the ASM has been to put comprehensive and valid statistics on the Australian use of medicines in the public domain to allow access by all interested parties. Publication of the Australian data facilitates international comparisons of drug utilisation profiles, and encourages international collaboration on drug utilisation research particularly in relation to enhancing the quality use of medicines and health outcomes. The data available in the ASM represent estimates of the aggregate community use (non public hospital) of prescription medicines in Australia. In 1997 the estimated number of prescriptions dispensed through community pharmacies was 179 million prescriptions, a level of increase over 1996 of only 0.4% which was less than the increase in population (1.2%).
    [Show full text]
  • EUROPEAN PHARMACOPOEIA 10.0 Index 1. General Notices
    EUROPEAN PHARMACOPOEIA 10.0 Index 1. General notices......................................................................... 3 2.2.66. Detection and measurement of radioactivity........... 119 2.1. Apparatus ............................................................................. 15 2.2.7. Optical rotation................................................................ 26 2.1.1. Droppers ........................................................................... 15 2.2.8. Viscosity ............................................................................ 27 2.1.2. Comparative table of porosity of sintered-glass filters.. 15 2.2.9. Capillary viscometer method ......................................... 27 2.1.3. Ultraviolet ray lamps for analytical purposes............... 15 2.3. Identification...................................................................... 129 2.1.4. Sieves ................................................................................. 16 2.3.1. Identification reactions of ions and functional 2.1.5. Tubes for comparative tests ............................................ 17 groups ...................................................................................... 129 2.1.6. Gas detector tubes............................................................ 17 2.3.2. Identification of fatty oils by thin-layer 2.2. Physical and physico-chemical methods.......................... 21 chromatography...................................................................... 132 2.2.1. Clarity and degree of opalescence of
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • I (Acts Whose Publication Is Obligatory) COMMISSION
    13.4.2002 EN Official Journal of the European Communities L 97/1 I (Acts whose publication is obligatory) COMMISSION REGULATION (EC) No 578/2002 of 20 March 2002 amending Annex I to Council Regulation (EEC) No 2658/87 on the tariff and statistical nomenclature and on the Common Customs Tariff THE COMMISSION OF THE EUROPEAN COMMUNITIES, Nomenclature in order to take into account the new scope of that heading. Having regard to the Treaty establishing the European Commu- nity, (4) Since more than 100 substances of Annex 3 to the Com- bined Nomenclature, currently classified elsewhere than within heading 2937, are transferred to heading 2937, it is appropriate to replace the said Annex with a new Annex. Having regard to Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Com- mon Customs Tariff (1), as last amended by Regulation (EC) No 2433/2001 (2), and in particular Article 9 thereof, (5) Annex I to Council regulation (EEC) No 2658/87 should therefore be amended accordingly. Whereas: (6) This measure does not involve any adjustment of duty rates. Furthermore, it does not involve either the deletion of sub- stances or addition of new substances to Annex 3 to the (1) Regulation (EEC) No 2658/87 established a goods nomen- Combined Nomenclature. clature, hereinafter called the ‘Combined Nomenclature’, to meet, at one and the same time, the requirements of the Common Customs Tariff, the external trade statistics of the Community and other Community policies concerning the (7) The measures provided for in this Regulation are in accor- importation or exportation of goods.
    [Show full text]
  • Pharmaceutical & Nutraceutical Actives
    PHARMACEUTICAL & NUTRACEUTICAL ACTIVES innovation beyond expertise ISALTIS innovation beyond expertise About us ISALTIS is a fine chemicals group mainly serving the life science markets. The group was formed late 2011, after the acquisition of BERNARDY (founded in 1950, ex-affiliate of SPCH) and GIVAUDAN-LAVIROTTE (founded in 1906, ex-affiliate of Seppic), benefiting from more than 100 years of expertise in the production of high purity mineral organic salts. We offer a large range of high quality products for pharmaceutical and nutraceutical applications: mineral supplementation, oral care, antifungal and rubefacients. The company is specialized in organic salts. Several studies have shown that such salts have a higher bioavailability and are better tolerated than the inorganic ones such as oxides, carbonates, sulfates, etc... Thanks to its commitments, Isaltis has become one of the high purity mineral salts key producers. We are operating on a worldwide basis and are exporting more than 80% of our products to over 50 countries on the five continents. Mineral supplementation ANI ONS Dynamic r ol e: bioa vailability facto r ASP AR TATE, G LUC ONA TE, GLUC OHE PT ONA TE, G LYCERO PHO SP HA TE, LACT ATE, CIT RA TE Minerals are essential nutrients that the body needs to properly carry out its daily functions and processes. They are crucial elements to all vital o rgans. Mineral deficiency occurs for many reasons (a lack in the diet, diffi culty to ab sorb from food or a simple increase in needs) and it can result in a variety of seriou s health problems. To avoid or treat several deficiencies, supplementation (oral or injectable) is the solution.
    [Show full text]
  • Liquid Foliar Nutritionals
    ® LIQUID FOLIAR NUTRITIONALS (800) 282-8007 Post Oce Box 807 | Lakeland, Florida 33802 Harrells.com | ©2018 Harrell’s LLC. All rights reserved. Employee-Owned Harrell’s Core Values • Serve, Honor, and Glorify God • Take Care of People • Grow Our Financial Strength Harrell’s Four Pillars • Humility • Gratitude • Intentionality • Accountability 8/2018 Harrell’s MAX® provides you results that get noticed. The complete line of Harrell’s MAX® liquid foliar nutritional products is an ideal way to complement your granular fertilization program. Foliar fertilizers feed through the leaves, crown, and roots, allowing for maximum plant uptake, less environmental loss through foliar application of stabilized nitrogen and lower nutrient loadings, and rapid green-up. The products may also be mixed with many pesticides and plant growth regulators for a labor-saving, one-step application. The Harrell’s MAX® product line has been specifically formulated to provide you with a complete and highly effective fertilizer portfolio. All foliar nutritional N, P & K components are derived from the finest foliar grade sources, allowing for maximum uptake and exceptional product quality. In addition, all Harrell’s MAX® micronutrient components have been chelated or complexed in order to maximize foliar absorption, increase tank-mix compatibility with other nutrients, and help protect these essential elements from environmental degradation. The line of Harrell’s MAX® liquid foliar nutritionals includes more than 30 different products, all engineered with innovative formulas that will provide outstanding results to help you grow dense and healthy turfgrass. Harrell’s incorporates UMAXX® stabilized nitrogen technology into many Harrell’s MAX® foliar products. UMAXX® is uniquely formulated with two proprietary enzyme blockers that minimize Nitrogen loss to the environment.
    [Show full text]
  • Cation-Complexed Polysaccharides
    Europaisches Patentamt J European Patent Office Oy Publication number: 0 648 495 A2 Office europeen des brevets EUROPEAN PATENT APPLICATION © Application number: 94111053.8 © int.Ci.6:A61K 31/715, A61K 9/10, A61 K 38/00 © Date of filing: 15.07.94 © Priority: 16.07.93 US 93231 © Applicant: HERCULES INCORPORATED 1313 N. Market Street, @ Date of publication of application: Hercules Plaza 19.04.95 Bulletin 95/16 Wilmington, Delaware 19894-0001 (US) © Designated Contracting States: AT BE CH DE DK ES FR GB IT LI NL PT SE @ Inventor: Barnum, Paquita Erazo 103 Neptune Drive/North Star Newark, Delaware 19711 (US) Inventor: Majewicz, Thomas George 610 Cope Road Kenneth Square, Pennsylvania 19348 (US) Representative: Hansen, Bernd, Dr. Dipl.-Chem. et al Hoffmann, Eitle & Partner, Patentanwalte, Arabellastrasse 4 D-81925 Munchen (DE) Cation-complexed polysaccharides. @ The present invention is a novel, water-insoluble, cation-complexed anionic polysaccharide that is readily dispersible into aqueous media to provide an ingestible composition having a low viscosity. An important aspect of the present invention is that it provides such compositions that are heat sterilizable. Furthermore, the water- insoluble, cation-complexed anionic polysaccharide of the present invention cause no or minor increases to the viscosity of such liquids that contain at least one member selected from the group consisting of proteins, CM peptides and amino acids. Another aspect of the invention concerns a method for administering an antidiarrheal < composition to a human, said antidiarrheal composition comprising at least one water-insoluble, cation- complexed anionic polysaccharide dispersed in an aqueous medium. These compositions are useful as a ID nutritional means of improving gastrointestinal function including bowel function and increasing absorption of organic nutrients, inorganic nutrients and water by the gastrointestinal tract.
    [Show full text]
  • United States Patent (19) 11) Patent Number: 4,867,977 Gailly Et Al
    United States Patent (19) 11) Patent Number: 4,867,977 Gailly et al. 45 Date of Patent: Sep. 19, 1989 54 CALCIUM SALTS 2,639,238 5/1953 Alther et al... ... 426/59 3,061445 10/1962 Stanish .......... ... 426/591 75 Inventors: Jean-Marc Gailly; Daniel Gomez; 3,082,091 3/1963 Smith ........ ... 426/591 Burguiéne Martine, all of Orléans; 3,105,792 10/1963 White ................ ... 424/44 André Gens, Olivet; Jean Remy, St. 3,241,977 3/1966 Mitchell et al... ... 424/44 Cyr en Val, all of France 3,328,304 6/1967 Globus .......... ... 424/156 3,489,572 1/1970 Kracauer....... ... 426/591 73 Assignee: Sandoz, Ltd., Basel, Switzerland 3,939,289 2/1976 Hornyak et al. ... 426/591 3,949,098 4/1976 Bangert ..... ... 426/590 21 Appl. No.: 67,311 3,965,273 6/1976 Stahl .......... ... 426/591 4,009,292 2/1977 Finucane ... ... 426/591 (22 Filed: Jun. 26, 1987 4,206,244 6/1980 Schenk .......... ... 426/588 (30) Foreign Application Priority Data 4,237,147 2/1980 Merten et al. ... 426/591 4,551,342 1/1985 Nakel et al. ....... ... 426/591 Jul. 1, 1986 FR France ................................. 8609515 4,650,669 3/1987 Alexander et al. ... 424/466 51) Int. Cl." ..................... A61K 33/06; A61K 33/10; 4,678,661 7/1987 Gergely et al. ....... ... 424/156 A61K 9/46 4,725,427 2/1988 Ashmead et al. ... 424/44 52 U.S. C. ...................................... 424/687 424/44; 4,760,138 7/1988 So et al. ................................ 424/44 424/466; 426/590; 426/591 Primary Examiner-Shep K.
    [Show full text]
  • United States Patent Office Patented May 8, 1962 2 Until the Effluent Is Reduced in Sodium Content to a Point 3,033,900 METHOD of PREPARING CALCIUM Below 0.4 Mg
    3,033,900 United States Patent Office Patented May 8, 1962 2 until the effluent is reduced in sodium content to a point 3,033,900 METHOD OF PREPARING CALCIUM below 0.4 mg. per milliliter of the effluent, calculated as GLUCOHEPTONATE sodium sulfate. The resulting effluent is treated with Arthur G. Holstein, Lake Bluff, ill, assignor to Pfansfieh sufficient calcium carbonate having a very low sulfate Laboratories, Inc., Waukegan, Ill., a corporation of impurity content, preferably below 0.05%, calculated linois as calcium sulfate to convert the glucoheptolactone and No Drawing. Filled Mar. 25, 1958, Ser. No. 723,671 its equilibrium component, glucoheptonic acid, to cal 8 Claims. (C. 260-535) cium glucoheptonate. During this conversion, the effluent is desirably heated, preferably to a temperature of about This invention relates to methods of preparing gluco O 80 C., in order to facilitate the conversion of the lactone heptonates and more particularly to novel improvements through the equilibrium component, glucoheptonic acid, in the preparation of calcium glucoheptonate. to the calcium salt of the acid. Activated carbon may be The preparation of a high purity calcium glucohepto added to the resulting solution to effect a reduction in nate for use in parenteral solutions has been difficult and the level of any residual color. The solution is then costly. Conventional methods involve the reaction of 15 filtered and evaporated under high vacuum to a specific glucose with hydrocyanic acid and conversion of the gravity of 1.45 or slightly higher. The resulting syrup nitrile thus formed into calcium glucoheptonate with cal is then run in a very fine stream into anhydrous methanol cium or barium hydrate.
    [Show full text]
  • Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes
    Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 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. Product CAS No. Product CAS No. ABACAVIR 136470-78-5 ACEXAMIC ACID 57-08-9 ABAFUNGIN 129639-79-8 ACICLOVIR 59277-89-3 ABAMECTIN 65195-55-3 ACIFRAN 72420-38-3 ABANOQUIL 90402-40-7 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABCIXIMAB 143653-53-6 ACITEMATE 101197-99-3 ABECARNIL 111841-85-1 ACITRETIN 55079-83-9 ABIRATERONE 154229-19-3 ACIVICIN 42228-92-2 ABITESARTAN 137882-98-5 ACLANTATE 39633-62-0 ABLUKAST 96566-25-5 ACLARUBICIN 57576-44-0 ABUNIDAZOLE 91017-58-2 ACLATONIUM NAPADISILATE 55077-30-0 ACADESINE 2627-69-2 ACODAZOLE 79152-85-5 ACAMPROSATE 77337-76-9 ACONIAZIDE 13410-86-1 ACAPRAZINE 55485-20-6 ACOXATRINE 748-44-7 ACARBOSE 56180-94-0 ACREOZAST 123548-56-1 ACEBROCHOL 514-50-1 ACRIDOREX 47487-22-9 ACEBURIC ACID 26976-72-7
    [Show full text]