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  • Pharmaceutical Compositions Containing Geminal Diphosphonates (US Patent 5583122)

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    U.S. patent 5583122: Pharmaceutical compositions containing geminal diphosphonates. Granted to Benedict et. al. (2 total) on 1996-12-10 (filed 1985-12-06) and assigned to The Procter & Gamble Company. Currently involved in at least 1 patent litigation: Warner Chilcott Company LLC et. al. v. Teva Pharmaceuticals USA Inc. (Delaware). See http://news.priorsmart.com for more info.

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    Pharmaceutical compositions containing geminal diphosphonates (US patent 5583122)

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    U.S. patent 5583122: Pharmaceutical compositions containing geminal diphosphonates. Granted to Benedict et. al. (2 total) on 1996-12-10 (filed 1985-12-06) and assigned to The Procter & Gamble Company. Currently involved in at least 1 patent litigation: Warner Chilcott Company LLC et. al. v. Teva Pharmaceuticals USA Inc. (Delaware). See http://news.priorsmart.com for more info.

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    Descărcați ca PDF sau citiți online pe Scribd
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    118 vizualizări12 pagini

    Pharmaceutical Compositions Containing Geminal Diphosphonates (US Patent 5583122)

    Încărcat de

    PriorSmart
    U.S. patent 5583122: Pharmaceutical compositions containing geminal diphosphonates. Granted to Benedict et. al. (2 total) on 1996-12-10 (filed 1985-12-06) and assigned to The Procter & Gamble Company. Currently involved in at least 1 patent litigation: Warner Chilcott Company LLC et. al. v. Teva Pharmaceuticals USA Inc. (Delaware). See http://news.priorsmart.com for more info.

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    United States Patent 1 Benedict et al. (ATTA IO 0 ‘US005583122A tn Patent Number 143) Date of Patent: 5,583,122 Dec. 10, 1996 (S4] PHARMACEUTICAL COMPOSITIONS CONTAINING GEMINAL DIPHOSPHONATES (75] Inventors: James J. Benedict, Norwich, N.Y; ‘Christopher M. Perkins, Cincinnati, Ohio [73] Assignee: ‘The Procter & Gamble Company, Cincinnati, Ohio [21] Appl. No: 806,185 [22] Filed: Dee. 6, 1985 Related U.S. Application Data (631. Coan part of Ser. No, 684548, Dee, 21,1984 anda (1) mas COTE 9/38; COTF 9/58; AGIK 31/675 [52] 514/89; 546/22 (58), 514189; 546/23, ‘546/23 (36) References Cited US. PATENT DOCUMENTS 3553314 1971 Francis aonus 3.683080 8/1972 Francis -siano7 3,846,420 11/1974. Wollman eta. *Saans7 3941,772 3/1976 Ploger etal. 54616 3.957.160 5/1976 Ploger etal. Sato 3.960388 6/1976 Ploger etal. savai2 3.979.385 9/1976. Wollmann ct a seanst 3.988443. 10/1976 Ploger eta. ‘14779 4034086 71977 Ploger eta. S149 2100167 7/978. Slvarsan eta 07296 R 4.117090 9/1978 4134969 979 4239,695 21980 2601502.5 457,108 s/1981 2601326.61, 4308734 12/1981 360/13 4407761 101983, OC Sean 447255 S984 “Tu86 4407256 i984 Tu86 4473560 9/1984 51495 4.503049 3/1985, 51480 4605,368 BV1986 sido? 4.621977 11/1986. Rosai et sia/ios 4.687.767 8/1987 Bosies oa 514/89 4.657.768 8/1987 Benedict etal. ~stanae 913987 Bentzea etal. s1a/s9 ¥ 1988. Bosies etl stanos ATTTIGS YONI9R8 Bosies eta 51480 FOREIGN PATENT DOCUMENTS: 88359 9/1983. Furopeen Pat. Of. 100718 170228 271986 23476 4/1975 2513966 10/1976 2saio81 3/1977 53.5967 S/1978 St1354 101979 35:98193 T1980 Japan 200888 4/1979 United Kingdom OTHER PUBLICATIONS C.A. vol. 93(1980) 93: 232711f, Nissan Chem. Ind CA. vol.93(1980) 93: 199,239h, Nissan Chem. Ind. ‘Worms QA. vol. 77 (1972) 130878N. C.A. vol. 94(1981) 94:11638F Nissan Chem. Ind, Francis & Martodam, “Chemical, Biochemical, & Medicinal Properties of the Diphosphonates", in The Role of Phospho- nates in Living Systems (CRC Prest; Hildesbrand editor), pp. 55-96 (1983). ‘Unterspann, “Experimental Examinations on the Suitability ‘of Organoaminomethane-bis-Phosphonic Acids for ‘Bone-Scintigraphy by Means of Te-99m in Animals", Bur. J. Nucl. Med., vol. 1, pp. 151-154 (1976). Sologub et al., “Synthesis and Intramolecular Electronic Interactions in Molecules of ‘Tetrachloropyridyl4-carbonimidey Dichloride and Its Derivatives”, Khim. Geteroisikl. Soedin, 1983, (6), pp. 798-800; abstract attached Chem. Abs. 99:122,246z. Maier, “Organophosphorous Compounds. Part 75", Phos- Phonis Sulfur, vol. 11 (3), pp. 311-22 (1981): abstract attached Chem. Abst. 96:52398n, plus article. Plocger etal, “Preparation of 1-Aminoalkylidene Diphos- Phonic Acids”, Z Anorg. Allg. Chem, vol. 389 (2), pp. 119-28 (1972); (original and English transleion attached), Grapoy etal, "Reaction of Ethyl-N-2-pyridylimidoformate with Dialkyiphosphites” Zk. Obshoh. Khim., vol. 57 (7) pp. 1655-1657 (1980); abstract attached Chena. Abst. 93:220, 8551. Bandurina et al, “Synthesis of Some Aminophosphonic Acids and Their Antineoplastic Activity”, Khim.-Farm. Zk, vol. 12 (11), pp. 35-37 (1978); Chem, Abst. 90:115,08 1c, 2984 European Pa. Of Enropean Pat. OF, Germany Germany Germany Japan Japan Primary Examiner—Nlan L. Rotman ‘Attomey, Agent, or Firm—K. W. Zerby; David L. Suter 137) ABSTRACT Pharmaceutical compositions, useful for treating abnormal calcium and phosphate metabolism, which contain geminal- diphosphonic acid compounds; and a method of treating diseases characterized by abnormal calcium and phosphale ‘metabolism utilizing these pharmaceutical compositions. 23 Claims, No Drawings 5,583,122 1 PHARMACEUTICAL COMPOSITIONS CONTAINING GEMINAL DIPHOSPHONATES. CROSS REFERENCE TO RELATED ‘APPLICATION This application is a Continustion-in-Part of prior appli cation Ser. No. 684,543, filed Dec. 21, 1984, now aban- doned. ‘TECHNICAL FIELD ‘This invention relates to pharmaceutical compositions containing compounds which are useful in treating or pre: venting diseases characterized by abnormal calcium and phosphate metabolism, in particular those which are clar- acterized by abnormal bone metabolism. This invention further relates to a method of treating or preventing diseases characterized by abnormal calcium and phosphate metabo- lism using pharmaceutical compositions of the present invention, BACKGROUND OF THE INVENTION ‘A number of pathological conditions which can aflict warm-blooded animals involve abnormal ealeum and phos ‘hat metabolism. Such conditions may be divided ino two broad categories. 1. Conkitions which are characterized by anomalous mobilization of ealeium and phosphate leading to general or specific bone loss or excessively high calcium and phos- phate levels in the fluids of the body. Such conditions are Sometimes refered to herein as pathological hard tissue emincralizations. 2. Conditions which cause or result from deposition of calcium and phosphate anomalously in the body. These conditions are sometimes refered to herein as pathological ealeiications. ‘The fst category includes osteoporosis, a condition in which bone hard tissue is lost disproportionate 10 the evelopment of new hard tissue, Marrow and bone spaces bocome lager, fibrous binding decreases, and compact bone becomes frapile. Ostcopoross canbe subelassifid as meno- pausal, senile, drug induced (¢., adrenocortcoid, as can ‘ceurin steroid therapy), disease induced (eg. arthritic and tumor), etc, however, the manifestations aze essentially the same. Another condition in the frst category is Paget's disease (osteitis deformans). In this disease, dissolution of normal bone occurs which is then haphazardly replaced by Soft, poorly mineralized tissue such thatthe bone becomes defomed from pressures of weight bearing, particularly in the tibia and femur. Hyperparathyroidism, hypercalcemia of ‘malignancy, and osteolyic bone metastases are conditions also included inthe first category. The second category, involving conditions manifested by anomalous calcium and. phosphate deposition, includes myositis ossificans progressiva, calcinosis universais, and such aflictions as arthritis, neuritis, bursitis, tendonitis and other inflammatory conditions which predigpose involved tissue to deposition of ealciam phosphates, Polyphosphonic acids and ther pharmacetially-sccept- able salts have been proposed for use in the treatment and prophylaxis of such conditions. In paricular diphospho- nates, Tike ethane-L-hydroxy-1,1-

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