DOCSLIB.ORG

United States Patent (19) 11 Patent Number: 4,765,973 Heller 45 Date of Patent: Aug

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
United States Patent (19) 11 Patent Number: 4,765,973 Heller 45 Date of Patent: Aug United States Patent (19) 11 Patent Number: 4,765,973 Heller 45 Date of Patent: Aug. 23, 1988 54) POLYMERS CONTAINING PEN DANT ACD Assistant Examiner-M. L. Moore FUNCTIONALITIES AND LABILE Attorney, Agent, or Firm-Manfred Polk; Michael C. BACKBONE BONDS Sudol (75) Inventor: Jorge Heller, Woodside, Calif. 57 ABSTRACT Assignee: Merck & Co., Inc., Rahway, N.J. The instant invention is directed to a polymer with at 73 least one labile backbone bond per repeat unit and at (21) Appl. No.: 915,348 least one pendant acid functionality per thousand repeat 22 Filed: Oct. 6, 1986 units. The instant invention is also directed to a controlled Related U.S. Application Data release device which comprises: (A) a polymer with at least one labile backbone bond (62) Division of Ser. No. 68,002, Jun. 6, 1984, Pat. No. per repeat unit and at least one pendant acid func 4,639,366. tionality per thousand repeat units; and 51 Int. Cl'.............................................. A61K 31/74. (B) a beneficial substance incorporated within or 52) U.S. C. ....................................... 424/486; 424/78 surrounded by the matrix of said polymer. (58) Field of Search ........................ 424/19, 20, 22, 78 Primary Examiner-John Kight 3 Claims, No Drawings 4,765,973 1. 2 Tri- and higher hydroxyl functional polyols may be POLYMERS CONTAINING PEN DANT ACID used, which will result in crosslinked polymers. FUNCTIONALTES AND LABLE BACKBONE Any polymer containing at least one acid labile back BONDS bone bond per repeat unit (preferably two per repeat 5 acid unit) may be used to react with the polyol contain This is a division of application Ser. No. 618,002 filed ing a pendant acid group. Examples include polyortho June 6, 1984 now U.S. Pat. No. 4,639,366. esters (including polyorthocarbonates), polyacetals, polyketals, polyesters and polyphosphazenes. The pre BACKGROUND OF THE INVENTION ferred polymers are poly(orthoesters) and polyacetals. There has long been a need in the field of drug deliv 10 Examples of polyorthoesters, polyorthocarbonates and ery devices to have a drug released in the human or polyacetals are disclosed in U.S. Pat. Nos. 4,093,709, animal tissue at the place where it is most therapeuti and 4,304,767, 4,221,779 and 4,150,108 which are cally effective and to have said drug released in the hereby incorporated by reference. tissue in a controlled manner over a long period of time. The preparation of the polymers may be by a variety U.S. Pat. Nos. 4,093,709 and 4,304,767 disclose poly 15 of methods. U.S. Pat. No. 4,093,709, column 8, line 11 mers which can be used as a matrix to contain a drug. through column 9, line 47, outlines several methods of The polymers contain labile backbone bonds which preparation. hydrolyze in the presence of water causing a controlled Any beneficial substance (e.g. therapeutics or biologi erosion of the matrix and resultant release of the drug. cally active agents) may be used in the controlled re These polymers have the disadvantage, however, that 20 lease device. The substance should not significantly they hydrolyze extremely slowly. interfere with the acid catalyzed hydrolysis of the labile The polymers of the instant invention have the ad polymer backbone bond. Basic substances may cause vantage that the pendant acid functionalities catalyze some interference. It is preferred that any acid sub the hydrolysis of the labile polymer backbone bonds. stances be in the salt form. 25 Representative examples of the polyols are as fol DESCRIPTION OF THE INVENTION lows: 9,10-dihydroxystearic acid; 3,6-dihydroxynaph The instant invention is directed to a polymer with at thalene-2,7-disulfonic acid; 2,4-dihydroxybenzoic acid; least one labile backbone bond per repeat unit and at 3,4-dihydroxycinnamic acid; 6,7-dihydroxy-2-naphtha least one pendant acid functionality per thousand repeat 30 lene sulfonic acid; 6,7-dihydroxy-2-naphtalene sulfenic units. acid; 2,5-dihydroxyphenylacetic acid; 2,4-dihydrox The instant invention is also directed to a controlled ypyrimidine-5-carboxylic acid; 4,8-dihydroxyquinoline release device which comprises: 2-carboxylic acid; and mixtures thereof. (A) a polymer with at least one labile backbone bond It will be realized that these are merely representative per repeat unit and at least one pendant acid func examples and that any polyol containing an acidic tionality per thousand repeat units; and 35 group can be used provided it does not adversely affect (B) a beneficial substance incorporated within or the polymerization reaction or leads to toxicologically surrounded by the matrix of said polymer. undesirable degradation products. Thus, any group that The polymers of the instant invention may be pre can be incorporated into the polymer and which when pared by reacting a polyol, preferably a diol, having a placed in water ionizes to produce a pH lower than pendant acidic group with a polymer containing a labile about 7.0 is a useful group provided the above limita backbone bond. Excess amounts of either component tions are met. may be used in preparing the final polymer, although The molecular weight of the polymer is not critical. stoichiometric amounts are preferred. The molecular weight is preferably at least 1,000 as U.S. Pat. Nos. 4,093,709 and 4,304,767, which are determined by low angle light scattering. hereby incorporated by reference, disclose numerous 45 Representative beneficial substances (therapeutics polyols. Any of these polyols may be modified to con and biologically active agents) for incorporation into or tain one or more pendant acidic groups per thousand to be surrounded by the polymer matrix to be used with repeat units, up to a maximum of one per repeat unit. this invention and to be released to an aqueous environ The number of acid groups incorporated depends on 50 ment include without limitation, the following: the desired rate of erosion. For increased erosion, rela 1. Protein drugs such as insulin; tively more acid groups would be incorporated. A pre 2. Desensitizing agents such as ragweed pollen anti ferred group of polyols may be represented as follows: gens, hay fever pollen antigens, dust antigen and milk antigen; 55 3. Vaccines such as smallpox, yellow fever, distem per, hog cholera, fowl pox, antivenom, scarlet fever, dyptheria toxoid, tetanus toxoid, pigeon pox, whooping cough, influenzae, rabies, mumps, measles, poliomyeli tis, Newcastle disease, etc.; 4. Anti-infectives, such as antibiotics, including peni where X is the acidic group and Y is a spacer group. R cillin, tetracycline, chlortetracycline bacitracin, nysta and Y may be an alkyl, aryl or substiuted alkyl or aryl, tin, streptomycin, neomycin, polymyxin, gramicidin, preferably containing 1 to 18 carbon atoms, most prefer oxytetracycline, chloramphenicol, and erythromycin; ably 2 to 10 carbon atoms. The Y group may optionally sulfonamides, including sulfacetamide, sulfamethizole, be eliminated. 65 sulfamethazine, sulfadiazine, sulfamerazine, and sulfi Any acidic group may be used in the polyol. Exam soxazole, cefoxitin; anti-virals including idoxuridine; ples include carboxylic, carbon acid, phosphoric, sul and other anti-infectives including nitrofurazone and fonic and sulfenic acid groups. sodium propionate; 4,765,973 3 4. 5. Antiallergenics such as antazoline, methapyrilene, nents of molecular complexes, or nonirritating, pharma chlorpheniramine, pyrilamine and prophenpyridamine; cologically acceptable salts such as hydrochloride, hy 6. Steroidal anti-inflammatory agents such as hydro drobromide, sulfate, phosphate, nitrate, borate, acetate, cortisone, cortisone, hydrocortisone acetate, dexameth maleate, tartrate, salicylate, etc. For acidic drugs, salts asone, dexamethasone 21-phosphate, fluocinolone, tri of metals, amines, or organic cations (e.g., quaternary amcinolone, medrysone, prednisolone, prednisolone ammonium) can be employed. Furthermore, simple 21-phosphate, and prednisolone acetate; derivatives of the drugs (such as ethers, esters, amides, 7. Decongestants such as phenylephrine, naphazoline, etc.) which have desirable retention and release charac and tetrahydrazoline; teristics but which are easily hydrolyzed by body pH, 8. Miotics such as pilocarpine, eserine salicylate, car 10 enzymes, etc., can be employed. bachol, diisopropyl fluorophosphate, phospholine io The amount of drug or beneficial substance incorpo dide, and demecarium bromide; rated into the polymer matrix will vary greatly depend 9. Anticholinergics such as atropine sulfate, cyclo ing on the particular drug, the desired therapeutic effect pentolate, homatropine, scopolamine, tropicamide, eu and the time span in which the polymer matrix is eroded catropine, and hydroxyamphetamine; 15 to release the particular drug. Thus, there is no critical 10. Sympathomimetics such as epinephrine; upper limit on the amount of drug incorporated in the 11. Sedatives and Hypnotics such as pentabarbital polymer matrix and the lower limit will also depend on sodium, phenobarbital, secobarbital sodium, codeine, the activity of the drug (usually at least 0.1%, prefera (a-bromoisovaleryDurea, carbromal; bly 0.1 to 30%, by weight, based on the total weight of 12. Psychic Energizers such as 3-(2-aminopropyl)in the device) and the time span for the erosion of the dole acetate, 3-(2-aminobutyl)indole acetate and ami polymer and subsequently the drug release. Thus, it is triptyline; not practical to define a range for the therapeutically 13. Tranquilizers such as reserpine, chlorpromazine, effective amount of drug to be incorporated in the novel thiopropazate and perphenazine; polymer matrixes of the instant invention. 14. Androgenic steroids such as methyltestosterone 25 Also in the case of the drug or other beneficial sub and fluorymesterone; stance incorporated into the polymer matrix as stated 15. Estrogens such as estrone, 17 g-estradiol, ethinyl above, the amount of drug or beneficial substance will estradiol, and diethyl stilbesterol; depend on the type of drug or substance for the condi 16. Progestational agents such as progesterone, tion being treated and can generally be up to 70% of the megestrol, melengestrol, chlormadinone, ethisterone, 30 polymer matrix by weight.
Load more

Recommended publications
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 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. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • 2020 Welldyne Formulary.Pdf
    LEGEND TIER DESCRIPTION 1 Preferred Generics 2 Non-Preferred Generics 3 Preferred Brands 4 Non-Preferred Brands 5 Preferred Specialty 6 Non-Preferred Specialty TYPE DESCRIPTION There is a limit on the amount of this drug that is covered per QL Quantity Limit prescription, or within a specific time frame. You (or your physician) are required to get prior authorization before PA Prior Authorization you fill your prescription for this drug. Without prior approval, we may not cover this drug. In some cases, you may be required to first try certain drugs to treat ST Step Therapy your medical condition before we will cover another drug for that condition. This prescription drug may only be covered if you meet the minimum AL1 Age Limit or maximum age limit. LA Limited Access This prescription drug is limited to certain pharmacies. Specialty drugs are high-cost drugs used to treat complex or rare S Specialty Drug conditions, such as multiple sclerosis, rheumatoid arthritis, hepatitis C, and hemophilia. PAGE 1 LAST UPDATED 01/2020 LIST OF COVERED PRESCRIPTION MEDICATIONS PRODUCT DESCRIPTION TIER LIMITS & RESTRICTIONS ADHD/ANTI-NARCOLEPSY /ANTI-OBESITY/ANOREXIANT AGENTS ADHD/ANTI-NARCOLEPSY/ANTI-OBESITY/ANOREXIANTS ADDERALL 4 AL1 Up to 25 yrs old ADDERALL XR 4 AL1 Up to 25 yrs old QL 30 / 30 day(s) ADHANSIA XR 4 AL1 Up to 25 yrs old QL 30 / 30 Days ADIPEX-P 4 PA QL 300 / 30 day(s) ADZENYS ER 4 AL1 Up to 25 yrs old QL 30 / 30 Days ADZENYS XR-ODT 4 AL1 Up to 25 yrs old QL 300 / 30 day(s) AMPHETAMINE ER 4 AL1 Up to 25 yrs old QL 180 / 30 day(s) amphetamine
    [Show full text]
  • Partial Agreement in the Social and Public Health Field
    COUNCIL OF EUROPE COMMITTEE OF MINISTERS (PARTIAL AGREEMENT IN THE SOCIAL AND PUBLIC HEALTH FIELD) RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies, and superseding Resolution AP (82) 2) AND APPENDIX I Alphabetical list of medicines adopted by the Public Health Committee (Partial Agreement) updated to 1 July 1988 APPENDIX II Pharmaco-therapeutic classification of medicines appearing in the alphabetical list in Appendix I updated to 1 July 1988 RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (superseding Resolution AP (82) 2) (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies) The Representatives on the Committee of Ministers of Belgium, France, the Federal Republic of Germany, Italy, Luxembourg, the Netherlands and the United Kingdom of Great Britain and Northern Ireland, these states being parties to the Partial Agreement in the social and public health field, and the Representatives of Austria, Denmark, Ireland, Spain and Switzerland, states which have participated in the public health activities carried out within the above-mentioned Partial Agreement since 1 October 1974, 2 April 1968, 23 September 1969, 21 April 1988 and 5 May 1964, respectively, Considering that the aim of the Council of Europe is to achieve greater unity between its members and that this
    [Show full text]
  • Demecarium Bromide/Homatropine 1881
    Demecarium Bromide/Homatropine 1881 Dyflos (BAN) junctival injection of pralidoxime has been used to reverse severe ocular adverse effects. Supportive treatment, including assisted DFP; Difluorophate; Di-isopropyl Fluorophosphate; Di-isopro- ventilation, should be given as necessary. CH3 pylfluorophosphonate; Fluostigmine; Isoflurofato; Isoflurophate. Di-isopropyl phosphorofluoridate. To prevent or reduce development of iris cysts in patients receiv- N ing ecothiopate eye drops, phenylephrine eye drops may be giv- C6H14FO3P = 184.1. en simultaneously. CAS — 55-91-4. ATC — S01EB07. Precautions ATC Vet — QS01EB07. As for Neostigmine, p.632. For precautions of miotics, see also OH under Pilocarpine, p.1885. In general, as with other long-acting anticholinesterases, ecothiopate should be used only where ther- O apy with other drugs has proved ineffective. Ecothiopate iodide CH3 should not be used in patients with iodine hypersensitivity. O O H3C O Interactions P CH3 As for Neostigmine, p.632. The possibility of an interaction re- O F mains for a considerable time after stopping long-acting anti- Homatropine Hydrobromide (BANM) CH3 cholinesterases such as ecothiopate. Homatr. Hydrobrom.; Homatropiinihydrobromidi; Homatropi- Pharmacopoeias. In US. Uses and Administration na, hidrobromuro de; Homatropine, bromhydrate d’; Homatro- USP 31 (Isoflurophate). A clear, colourless, or faintly yellow liq- Ecothiopate is an irreversible inhibitor of cholinesterase; its ac- pin-hidrobromid; Homatropinhydrobromid; Homatropin-hydro- uid. Specific gravity about 1.05. Sparingly soluble in water; sol- tions are similar to those of neostigmine (p.632) but much more bromid; Homatropini hydrobromidum; Homatropinium Bro- uble in alcohol and in vegetable oils. It is decomposed by mois- prolonged. Its miotic action begins within 1 hour of its applica- mide; Homatropino hidrobromidas; Homatropinum Bromatum; ture with the evolution of hydrogen fluoride.
    [Show full text]
  • Pharmacology of Ophthalmologically Important Drugs James L
    Henry Ford Hospital Medical Journal Volume 13 | Number 2 Article 8 6-1965 Pharmacology Of Ophthalmologically Important Drugs James L. Tucker Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal Part of the Chemicals and Drugs Commons, Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Tucker, James L. (1965) "Pharmacology Of Ophthalmologically Important Drugs," Henry Ford Hospital Medical Bulletin : Vol. 13 : No. 2 , 191-222. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol13/iss2/8 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. For more information, please contact [email protected]. Henry Ford Hosp. Med. Bull. Vol. 13, June, 1965 PHARMACOLOGY OF OPHTHALMOLOGICALLY IMPORTANT DRUGS JAMES L. TUCKER, JR., M.D. DRUG THERAPY IN ophthalmology, like many specialties in medicine, encompasses the entire spectrum of pharmacology. This is true for any specialty that routinely involves the care of young and old patients, surgical and non-surgical problems, local eye disease (topical or subconjunctival drug administration), and systemic disease which must be treated in order to "cure" the "local" manifestations which frequently present in the eyes (uveitis, optic neurhis, etc.). Few authors (see bibliography) have attempted an introduction to drug therapy oriented specifically for the ophthalmologist. The new resident in ophthalmology often has a vague concept of the importance of this subject, and with that in mind this paper was prepared.
    [Show full text]
  • Order in Council 1243/1995
    PROVINCE OF BRITISH COLUMBIA ORDER OF THE LIEUTENANT GOVERNOR IN COUNCIL Order in Council No. 12 4 3 , Approved and Ordered OCT 121995 Lieutenant Governor Executive Council Chambers, Victoria On the recommendation of the undersigned, the Lieutenant Governor, by and with the advice and consent of the Executive Council, orders that Order in Council 1039 made August 17, 1995, is rescinded. 2. The Drug Schedules made by regulation of the Council of the College of Pharmacists of British Columbia, as set out in the attached resolution dated September 6, 1995, are hereby approved. (----, c" g/J1"----c- 4- Minister of Heal fandand Minister Responsible for Seniors Presidin Member of the Executive Council (This pan is for adnwustratlye purposes only and is not part of the Order) Authority under which Order Is made: Act and section:- Pharmacists, Pharmacy Operations and Drug Scheduling Act, section 59(2)(1), 62 Other (specify): - Uppodukoic1enact N6145; Resolution of the Council of the College of Pharmacists of British Columbia ("the Council"), made by teleconference at Vancouver, British Columbia, the 6th day of September 1995. RESOLVED THAT: In accordance with the authority established in Section 62 of the Pharmacists, Pharmacy Operations and Drug Scheduling Act of British Columbia, S.B.C. Chapter 62, the Council makes the Drug Schedules by regulation as set out in the attached schedule, subject to the approval of the Lieutenant Governor in Council. Certified a true copy Linda J. Lytle, Phr.) Registrar DRUG SCHEDULES to the Pharmacists, Pharmacy Operations and Drug Scheduling Act of British Columbia The Drug Schedules have been printed in an alphabetical format to simplify the process of locating each individual drug entry and determining its status in British Columbia.
    [Show full text]
  • Pharmaceuticals As Environmental Contaminants
    PharmaceuticalsPharmaceuticals asas EnvironmentalEnvironmental Contaminants:Contaminants: anan OverviewOverview ofof thethe ScienceScience Christian G. Daughton, Ph.D. Chief, Environmental Chemistry Branch Environmental Sciences Division National Exposure Research Laboratory Office of Research and Development Environmental Protection Agency Las Vegas, Nevada 89119 [email protected] Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Why and how do drugs contaminate the environment? What might it all mean? How do we prevent it? Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada This talk presents only a cursory overview of some of the many science issues surrounding the topic of pharmaceuticals as environmental contaminants Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada A Clarification We sometimes loosely (but incorrectly) refer to drugs, medicines, medications, or pharmaceuticals as being the substances that contaminant the environment. The actual environmental contaminants, however, are the active pharmaceutical ingredients – APIs. These terms are all often used interchangeably Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Office of Research and Development Available: http://www.epa.gov/nerlesd1/chemistry/pharma/image/drawing.pdfNational
    [Show full text]
  • Nucleosides, Nucleotides, Heterocyclic Compounds, Pyridine 2013
    Nucleosides, Nucleotides, Heterocyclic Compounds, Pyridine, Pyrimidine, Azaindole, Quinoline, Thiazole, Isatin, Phenanthrene, Thiophene We declare that some of the listed products might be protected by valid patents. They are only for scientific research and development purpose. They are not offered for sales in countries where the sales of such products constitutes patents infringement. The liability for patents checking and patents infringement is exclusive at buyers risk! I2CNS LLC CANNOT BE HELD LIABLE FOR ANY VIOLATIONS OF PATENT RIGHTS CAUSED BY CUSTOMERS. CAS No. Product Name and Description 26988-72-7 1-METHYL-DL-TRYPTOPHAN 68886-07-7 2-Fluoro-4-hydroxyphenylaceticacid 72607-53-5 N-(3-AMINOPROPYL)METHACRYLAMIDE 171049-41-5 7-AMINO-3,4-DIHYDRO-1H-ISOQUINOLINE-2-CARBOXYLICACIDTERT- BUTYLESTER 885280-38-6 (3-OXO-CYCLOHEXYL)-CARBAMICACIDTERT-BUTYLESTER 186826-86-8 MOXIFLOXACIN HCL 102735-53-5 L-CYCLOPROPYLALANINE 145100-50-1 2-[N,N-BIS(TRIFLUOROMETHYLSULFONYL)AMINO]PYRIDINE 143491-57-0 Emtricitabine 39809-25-1 2-Amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-3,9-dihydropurin-6-one 147127-20-6 Tenofovir 716-39-2 2,3-NAPHTHALENEDICARBOXYLICANHYDRIDE 4333-62-4 1,3-DIMETHYLIMIDAZOLIUMIODIDE 108-45-2 m-Phenylenediamine 1961-72-4 R-(3)-HYDROXYMYRISTICACID 131-48-6 N-Acetylneuraminicacid 88196-70-7 (R)-1-(3-Methoxyphenyl)ethylamine 680-31-9 Hexamethylphosphoramide 486-66-8 Daidzein 872-50-4 1-Methyl-2-pyrrolidinone 425378-68-3 2-FLUORO-5-NITROPHENYLBORONICACIDPINACOLESTER 115651-29-1 5-ACETYL-2-AMINO-4-HYDROXYBENZOICACID 115269-99-3 N,N-BIS-BOC-N-ALLYLAMINE
    [Show full text]
  • Independent Cholinergic and Adrenergic Mechanisms in the Guinea-Pig Isolated Nerve Vas Deferens Preparation by K
    Brit. J. Pharmacol. (1965), 24, 641-650. INDEPENDENT CHOLINERGIC AND ADRENERGIC MECHANISMS IN THE GUINEA-PIG ISOLATED NERVE VAS DEFERENS PREPARATION BY K. P. BHARGAVA, K. KAR AND SURENDRA S. PARMAR From the Upgraded Department of Pharmacology and Therapeutics, K.G. Medical College, Lucknow University, India (Received July 28, 1964) Hukovic (1961) described the responses of the guinea-pig isolated vas deferens to hypogastric nerve stimulation. Anatomically the vas deferens seems to be exclusively sympathetically innervated. The hypogastric nerve is predominantly composed of non- myelinated C fibres (Burnstock & Holman, 1961). The presence of catechol amines (predominantly noradrenaline) has been demonstrated in the guinea-pig vas deferens (Sjbstrand, 1962b; Falck, 1962). Appropriately high doses of adrenergic blocking agents prevent the responses of the isolated vas deferens to nerve stimulation (Boyd, Chang & Rand, 1960). Contrary to the finding of Boyd et al. (1960) that 0.1 ,ug/ml. of atropine reduced the responses to hypogastric nerve stimulation, Chang & Rand (1960) reported that high concentrations of atropine (3.0 ,ug/ml.) had no such effect. Treatment of the animal with reserpine diminishes the effect of hypogastric nerve stimulation and the reduction can be reversed by noradrenaline (Hukovic, 1961). Bretylium and guanethidine block the response to nerve stimulation (Boyd, Chang & Rand, 1961). There is evidence for a cholinergic mechanism in sympathetic nerves to many organs including the vas deferens (Boyd et al., 1960). Choline acetylase (Ohlin & Str6mblad, 1963) and cholinesterase (Boyd et al., 1960) have been demonstrated in the vas deferens. The results obtained with the cholinesterase inhibitors (physostigmine and neostigmine) also support a cholinergic mechanism in the sympathetic innervation to this organ (Boyd et al., 1960; Bentley, 1962; Riley & Maanen, 1962; Burn & Weetman, 1963; Ohlin & Stromblad, 1963).
    [Show full text]
  • Centene Employee
    Centene Employee PREFERRED DRUG LIST The Centene Employee Formulary includes a list of drugs covered by your prescription benefit. The formulary is updated often and may change. To get the most up-to-date information, you may view the latest formulary on our website at https://pharmacy.envolvehealth.com/members/formulary.html or call us at 1-844-262-6337. Updated: December 1, 2020 Table of Contents What is the Centene Employee Formulary?...................... .....................................................................ii How are the drugs listed in the categorical list?................................... .................................................ii How much will I pay for my drugs?.......................................................................................................ii How do I find a drug on the Drug List?..................................................................................................iii Are there any limits on my drug coverage?.............................................................................................iv Can I go to any pharmacy?......................................................................................................................iv Can I use a mail order pharmacy?...........................................................................................................v How can I get prior authorization or an exception to the rules for drug coverage?................................v How can I save money on my prescription drugs?.................................................................................v
    [Show full text]
  • Acetylcholinesterase
    AChE Acetylcholinesterase Acetylcholinesterase (AChE or acetylhydrolase) is a hydrolase that hydrolyzes the neurotransmitter acetylcholine. AChE is found at mainly neuromuscular junctions and cholinergic brain synapses, where its activity serves to terminate synaptic transmission. It belongs tocarboxylesterase family of enzymes. It is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides. AChE has a very high catalytic activity - each molecule of AChE degrades about 25000 molecules ofacetylcholine (ACh) per second, approaching the limit allowed by diffusion of the substrate. ACh is released from the nerve into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE, also located on the post-synaptic membrane, terminates the signal transmission by hydrolyzing ACh. The liberated choline is taken up again by the pre-synaptic nerve and ACh is synthetized by combining with acetyl-CoA through the action of choline acetyltransferase. www.MedChemExpress.com 1 AChE Inhibitors & Activators (+)-Phenserine (-)-Corynoxidine Cat. No.: HY-16009 Cat. No.: HY-N7010 (+)-Phenserine is a novel selective cholinesterase (-)-Corynoxidine is an acetylcholinesterase noncompetitive inhibitor with an IC50 of 45.3 μM. inhibitor with an IC50 value of 89.0 μM, isolated from the aerial parts of Corydalis speciosa. (-)-Corynoxidine exhibits antibacterial activities against Staphylococcus aureus and methicillin-resistant S. Purity: 98.09% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 5 mg, 10 mg, 50 mg Size: 1 mg, 5 mg (-)-Huperzine A (R)-Rivastigmine D6 tartrate (Huperzine A) Cat. No.: HY-17387 Cat. No.: HY-11017AS (-)-Huperzine A (Huperzine A) is an alkaloid (R)-Rivastigmine D6 tartrate is the deuterium isolated from a Chinese club moss, with labeled (R)-Rivastigmine, which is an neuroprotective activity.
    [Show full text]