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United States Patent (19) 11 Patent Number: 4,722,938 Sunshine Et Al

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United States Patent (19) 11 Patent Number: 4,722,938 Sunshine Et Al United States Patent (19) 11 Patent Number: 4,722,938 Sunshine et al. (45. Date of Patent: Feb. 2, 1988 (54 METHODS FOR USING 82,717, copy of patent and English translation thereof; MUSCULOSKELETAL RELAXANTS (10/83). Rego, "Mio-Relaxantes No Tratmento Das Lombalgias 75 Inventors: Abraham Sunshine, New York; Agudas E Das Lombo-Ciaticas Recentes'Muscle Re Eugene M. Laska, Larchmont; laxants in the Treatment of Acute Lumbalgias and Re Carole E. Siegel, Mamaroneck, all of cent Lumbo-Sciatica Cases, Acta Reumatologica Por N.Y. tuguesa, II, 2:363-364, (1974), copy of the original and English translation thereof. 73 Assignee: Analgesic Associates, Larchmont, Schror, "Analgetisch-Antiphlogistische Therapie Von N.Y. Schmerzzustanden des Bewegungsapparates'Anal 21 Appl. No.: 815,502 gesic-Antiphlogistic Therapy of Locomotor System Pain), Therapiewoche, 28, 5657-5663, (1978), copy of the (22 Filed: Jan. 2, 1986 original and English translation thereof. Schar, "Medikamentose Behandlung von Lumbois Related U.S. Application Data chialgien'Drug Treatment of the Lumbago-Sciatic Syndrome), Schweiz, Rundschau Med. (Praxis), vol. 68, 63 Continuation of Ser. No. 686,380, Dec. 26, 1984, aban No. 5, pp. 141-142, (Jan. 30, 1979), copy of original doned. article and English translation thereof. 51 Int. Cl....................... A61K 31/19; A61K 31/27 Kolodny and Klipper, "Bone and Joint Diseases in the Elderly', Hospital Practice, pp. 91-101, (Nov. 1976). (52) - O - 514/479; 514/568 Nascimento, "Use of an Association Containing an An 58 Field of Search ................................ 514/568, 479 algesic, a Muscle Relaxant and Vitamin B Complex in (56) References Cited Degenerative Joint Diseases, Extra-Articular Rheu matic Ailments and Traumatic Afflictions', F med, FOREIGN PATENT DOCUMENTS (BR), 83(3):361-363, (1981), original article and English 2121529 12/1971 France. translation thereof. Repschlaeger and McPherson, "Classification, Mecha OTHER PUBLICATIONS nism and Management of Headache", Clinical Phar Armas & Valencia, "Eficacia Terapeutica de la Asocia macy, vol. 3, pp. 139-150, (Mar.-Apr. 1984). cion Naproxen-Carisoprodol en Ciertas Enfermedader Musculoesqueleticas"Therapeutic Effectiveness of Na Primary Examiner-Stanley J. Friedman proxen-Carisoprodol Association in Certain Musculo Attorney, Agent, or Firm-Burns, Doane, Swecker & skeletal Disorders, in Investigation Medica Interna Mathis cional, pp. 350-356, (1983), and English translation (57) ABSTRACT thereof. Novel pharmaceutical analgesic, anti-inflammatory and Goti & Valencia, "Caracterizacion Clinica de Una skeletal muscle relaxant compositions and methods of Nueva Asociacion (Naproxen -- Carisoprodol) en using same comprising an analgesically and anti-inflam Padecimientos del Aparato Musculoesqueletico'Clini matory effective amount of at least one non-steroidal cal Description of a New Association (Naproxen -- anti-inflammatory drug other than aspirin, acetamino Carisoprodol) in Ailments of the Musculoskeletal Ap phen and phenacetin, in combination with an effective paratus, Investigation Medica Internacional, pp. amount of a skeletal muscle relaxant. 475-478, (1983), and English translation thereof. Socialist Republic of Romania Description of Invention 19 Claims, No Drawings 4,722,938 1. 2 and diarrhea. Allergic type reactions associated with METHODS FOR USENG MUSCULOSKELETAL aspirin may also involve the respiratory tract and skin. RELAXANTS Another commercial skeletal muscle relaxant formu lation is Parafon Forte (R) by McNeil Pharmaceutical. This application is a continuation of application Ser. 5 Parafon Forte contains 250 mg chlorzoxazone and 300 No. 686,380, filed Dec. 26, 1984, now abandoned. mg acetaminophen. ChlorZoxazone is a centrally-acting agent which does not directly relax tense skeletal mus BACKGROUND OF THE INVENTION cles in man. Acetaminophen, a nonsalicylate analgesic, 1. Field of the Invention is a conventional non-narcotic analgesic with anti The present invention relates generally to novel phar 10 pyretic activity. maceutical compositions of matter comprising one or Robaxisal (R) by A. H. Robins Company, Inc. is an more non-steroidal anti-inflammatory drugs in combi other commercial muscle relaxant formulation which nation with at least one skeletal muscle relaxant, and to contains 400 mg methocarbamol and 325 mg aspirin. methods of using said compositions in the treatment of The mechanism of action of methocarbamol in humans a variety of skeletal muscle disorders including skeletal 15 has not been established, but may be due to general muscle spasms, certain orthopedic conditions, disk syn central nervous system depression. Methocarbamol dromes, low back pain and the like. does not directly relax tense skeletal muscles in man. 2. Description of the Prior Art Adverse reactions that have been associated with aspi Centrally acting skeletal muscle relaxants are gener rin in this formulation include: nausea and other gastro ally prescribed either as single agents or as components 20 intestinal discomfort, gastritis, gastric erosion, vomit of combination products. The Food and Drug Adminis ing, constipation, diarrhea, angioedema, asthma, rash, tration has approved indications for these medications pruritis and urticaria. as adjuncts to rest and physical therapy for relief of Norgesic (E) and Norgesic (R) Forte are commercial acute, painful musculoskeletal problems. Clinically, the products by Riker Laboratories, Inc. that contain a mild pain associated with the majority of cases of minor 25 muscle relaxant, aspirin and caffeine. The specific for muscle strains and minor injuries is self limiting. Most mulation for Norgesic is 25 mg orphenadrine citrate, patients usually respond rapidly to rest. An anti-inflam 385 mg aspirin and 30 mg caffeine. Norgesic Forte matory drug may be useful when there is considerable contains 50 mg orphenadrine citrate, 770 mg aspirin and tissue damage and edema. On the other hand, severe 60 mg caffeine. Orphenadrine citrate is 2-dime musculoskeletal strains and sprains, trauma, and cervi 30 thylaminoethyl 2-methylbenzhydryl ether citrate. The cal or lumbar radiculopathy as a consequence of degen common side effects and concerns associated with the erative osteoarthritis, herniated disk, spondylitis or lam use of aspirin occur with the use of Norgesic and Nor inectomy, often cause moderate or severe and more gesic Forte as well. TABLE I Some Combination Products Containing a Skeletal Muscle Relaxant CONTENTS OF A SINGLE TABLET TYPICAL DOSAGE SKELETAL MUSCLE ADDITIONAL PRESENTED AS TRADENAME RELAXANT INGREDIENTS NO. OF TABLETS SOMA COMPOUND Carisoprodol 200 mg aspirin 325 mg 1-2 SOMA COMPOUND Carisoprodol 200 mg aspirin 325 mg WITH CODENE codeine PO4 16 mg 1-2 PARAFON FORTE Chlorzoxazone 250 mg acetaminophen 300 mg 1-2 ROBAXISAL Methocarbamol 400 mg aspirin 325 mg 2 NORGESC Orphenadrine aspirin 385 mg Citrate 25 mg caffeine 30 mg 1-2 NORGESICFORTE Orphenadrine aspirin 770 mg Citrate 50 mg caffeine 60 mg -l chronic painful skeletal muscle spasm. The principal symptoms include local pain, tenderness on palpation, 50 At the present time, one commercial product, Para increased muscle consistency and limitation of motion. fon Forte, a skeletal muscle relaxant formulation con For these patients skeletal muscle relaxants alone or in taining acetaminophen, will be the subject of a hearing combination with an analgesic are frequently pre granted by the Commissioner of Food and Drugs on a scribed. Results of some studies have suggested that a proposal to withdraw approval of its new drug applica formulation of a muscle relaxant and an analgesic pro 55 tion sometime in 1985. The Director of the Bureau of vides greater benefit in patients with acute musculoskel Drugs of the FDA in a notice published in the Federal etal problems than similar doses of an analgesic alone. Register, 1982, 47 F.R. 22599 concluded that he was Table I lists several commercial combinations avail unaware of any adequate and well-controlled clinical able. A current commercial muscle relaxant formulation investigation conducted by experts qualified by scien is Soma (8) Compound by Carter-Wallace, Inc. which tific training and experience... that demonstrates the contains 200 mg carisoprodol and 325 mg aspirin. Cari effectiveness of Parafon Forte. The present position of soprodol is a centrally-acting muscle relaxant that does the Commissioner of Food and Drugs is set forth below not directly relax tense skeletal muscles in man. Aspirin Federal Register, 1984, 49(200): 48212-482.14): is a conventional non-narcotic analgesic with anti-in flammatory and antipyretic activity. The most common 65 Approval of this NDA will be withdrawn unless adverse reactions associated with the use of aspirin in there exists substantial evidence that Parafon Forte this product have been gastrointestinal, including nau has the clinical effect that it purports or is repre sea, vomiting, gastritis, occult bleeding, constipation sented to have under the conditions of use pre 4,722,938 3 4. scribed, recommended, or suggested in its labeling DETAILED DESCRIPTION OF THE INVENTION It should be noted that all of the previously described More specifically, the applicants herein have surpris skeletal muscle relaxant/non-narcotic analgesic formu- 5 ingly found that certain newer non-steroidal anti-in lations include either aspirin or acetaminophen as the flammatory agents are ideally suited for use in a formu non-narcotic analgesic agent. However, a number of lation with skeletal muscle relaxants by reason
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