Crystalline disodium 3-amino-1-hydroxypropane-1,1-diphosphonate pentahydrate

• US 4,711,880 A
• Filed: 09/08/1986
• Issued: 12/08/1987
• Est. Priority Date: 08/06/1984
• Status: Expired due to Term

• Current Assignee: Novartis Corporation (Novartis Ag)
• Original Assignee: Henkel KGaA (Henkel AG & Co KGaA), Ciba-Geigy Corporation (Novartis Ag)
• Inventors: Schmitz, Beat, Stahl, Peter H.
• Primary Examiner(s): Evans, J. E.
• Application Number:
  US06/905,097
• Time in Patent Office: 456 Days
• Field of Search: 260/502.5 C, 514/108
• US Class Current: 514/103
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: C07F 9/3873 containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)

Abstract

The invention relates to a novel crystal modification, containing water of crystallization, of disodium 3-amino-1-hydroxypropane-1,1-diphosphonate of the formula ##STR1## and to a process for the manufacture thereof. This modification is suitable for the oral treatment of disorders of the calcium and phosphate metabolism and associated diseases in warm-blooded animals.

Claims

1. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate of the formula ##STR3## in a crystalline form that contains water of crystallisation.

2. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate in a crystalline form that contains water of crystallisation according to claim 1, characterised by a water content of from approximately 24.1 to approximately 24.5% by weight.

3. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate according to claim 1 in crystalline pentahydrate form.

4. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate according to claim 1, obtainable by crystallisation of disodium 3-amino-1-hydroxypropane-1,1-diphosphonate from a water-containing solution and drying at normal or slightly elevated temperature.

5. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate according to claim 1, obtainable by crystallisation from an at least saturated aqueous solution, crystal formation taking place at at least approximately 50°

C., and drying at from approximately 15°

C. to approximately 60°

C.

6. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate according to claim 1, obtainable by crystallisation from an at least saturated aqueous solution, crystal formation taking place at from approximately 50°

C. to approximately 80°

C., and drying at from approximately 18°

C. to approximately 25°

C. or at from approximately 35°

C. to approximately 40°

C.

7. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate according to claim 1, obtainable by the action of moist air having a relative atmospheric humidity of from approximately 95% to approximately 99% at from approximately 20°

C. to approximately 25°

C.

8. Disodium 3-amino-1-hydroxypropane-1,1-diphosphonate in a crystalline form that contains water of crystallisation according to claim 1, characterised by the following lattice spacings (d-values) and relative line intensities (intensities) of its X-ray powder pattern (camera according to Guinier-de-Wolff, radiation source:

copper-K.sub.α

);

space="preserve" listing-type="tabular">______________________________________ d-values (Å

ngstrom) Intensities ______________________________________ 10.2 medium 9.9 medium 9.2 very strong 5.91 very strong 5.57 strong 5.42 very weak 5.30 strong 5.14 medium 5.02 very strong 4.97 very strong 4.63 very weak 4.41 strong 4.16 strong 4.07 weak 4.04 medium 3.95 very weak 3.75 strong 3.67 weak 3.63 medium 3.61 very weak 3.58 very weak 3.51 medium 3.43 strong 3.38 medium 3.15 medium 3.14 medium 3.09 medium 3.03 very strong 3.01 very strong 2.98 strong 2.97 very weak 2.91 very strong 2.82 strong 2.80 medium 2.78 medium 2.75 strong 2.73 weak 2.71 weak 2.69 weak 2.67 medium 2.66 medium 2.63 strong 2.62 strong 2.61 strong 2.58 very strong 2.57 very strong ______________________________________

9. Pharmaceutical preparations intended for enteral administration to warm-blooded animals, containing disodium 3-amino-1-hydroxypropane-1,1-diphosphonate in addition to customary pharmaceutical auxiliaries, characterised in that they contain the mentioned active ingredient in a crystalline form that contains water of crystallisation according to claim 1.