1. Field of the Invention
Bisphosphonates--synthetic compounds containing two phosphonate groups bound to a carbon and two additional groups R.sub.1 and R.sub.2, respectively (see formula A herebelow)--bind strongly to calcium crystals, inhibit their growth, suppress bone resorption and are used in the treatment of a variety of disorders of calcium and bone metabolism. It is generally considered that the "bone hook" (P-C-P with R.sub.1) is responsible for the binding of these molecules to mineralized matrices, while, in turn, the R.sub.2 group is primarily responsible for its effect on bone resorption. ##STR2##
2. Description of the Related Art
U.S. Pat. No. 4,054,598 discloses a method with sequestering agents, especially for alkaline earth metal ions, having the formula 1-hydroxy-3-amino-alkane-1,1-bisphosphonic acids, useful for the treatment of disturbances of calcium or phosphate metabolism characterized by abnormal deposition of difficultly soluble calcium salts or the abnormal dissolution of hard tissues causing losses of hard bone substance, which cannot be replaced or only by incompletely crystallized tissues, such as Paget's disease, lithiasis, arthritis and others. Spanish Patent No. P910088 discloses pharmaceutical liposome preparations containing bisphosphonates as active compounds. The use of olpadronate as an anabolic agent for the treatment of osteoporosis and other bone metabolism disorders is claimed in the Applicant's earlier PCT application PCT/EP95/05142.
A number of 1,3-diaminoalkane-1,1-bisphosphonic acids including, amongst others, 1-amino-3-(N,N-dimethylamino)-propyliden-1,1-bisphosphonic acid are disclosed in DE-A1-25 34 390. Several applications (medical and non-medical), unrelated to the claimed methods of use of the present application, are mentioned, without giving any specific advantages for 1-amino-3-(N,N-dimethylamino)-propyliden-1,1-bisphosphonic acid.
DE-A1-18 13 659 is directed to compositions for the inhibision of deposition and mobilisation of calcium phosphate in tissues with an effective, but non-toxic content of various polyphosphonates. However, the specific compound of the present application is not mentioned.
In Eur. J. Clin. Invest. 1970, Vol. 1 (1) pp. 12-18 (Fleisch et al.) the inhibitory effect of phosphonates on the formation of calcium phosphate crystals in vitro and an aortic and kidney calcification in vivo is described. However, the specific compound of the present application is not mentioned.
DE-C1-10 02 355 is directed to processes for the production of various bisphosphonates. However, the specific compound of the present application is not mentioned. Moreover, no specific applications for the described compounds are given.
Z. Anorg. Allg. Chem. 389, pp. 119-128 (1972) (Ploger et al.) is directed to different processes for the production of various bisphosphonates, however without mentioning the specific compound of the present application or any specific application of the described compounds at all.
CA-A1-21 20 538 discloses the use of bisphosphonic acid derivatives for promoting bone repair. Although the general formula would also cover the specific compound of the present application, this compound or any related advantages are not mentioned in the description.
It is the object of the invention to provide for specific new medical applications of 1-amino-3-(N,N-dimethylamino)-propyliden-1,1-bisphosphonic acid or its monosodium or other pharmaceutically acceptable salt.