The present disclosure is directed to fatty-acid glycerol ester derivative compounds containing a targeting bisphosphonate group. The disclosure further includes pharmaceutical or biomedical compositions comprising these compounds, and methods of using these compounds and compositions forming microbubbles. The microbubbles have affinity for metal-containing, especially calcium-containing, bodies and/or biological targets. In certain embodiments, these compositions are useful for providing targeted placement of microbubbles capable of cavitation on application of high frequency energy.

A magnetic resonance imaging (MRI) contrast agent and a preparation method and a use thereof is provided, which belong to the technical field of Magnetic Resonance Imaging contrast agent. The MRI contrast agent is prepared by the compound having a structure of formula I; and it also may include the compound having a structure of formula II or a pharmaceutically acceptable salt thereof, wherein M.sub.1 is a divalent ion or a trivalent ion of a paramagnetic metal selected from Mn, Fe, Eu, or Dy; M.sub.2 is selected from Na.sup.+, K.sup.+ or meglumine cation; when M.sub.1 is a divalent ion, a is 2; when M.sub.1 is a trivalent ion, a is 3. The MRI contrast agent has good water solubility, high relaxivity, and low toxic and side effect.

##STR00001##

The invention relates to a marking precursor incorporating a chelator or fluorination group for radiolabelling with .sup.44Sc, .sup.47Sc, .sup.55Co, .sup.62Cu, .sup.64Cu, .sup.67Cu, .sup.66Ga, .sup.67Ga, .sup.68Ga, .sup.89Zr, .sup.86Y, .sup.90Y, .sup.90Nb, .sup.99mTc, .sup.111In, .sup.135Sm, .sup.140Pr, .sup.159Gd, .sup.149Tb, .sup.160Tb, .sup.161Tb, .sup.165Er, .sup.166Dy, .sup.166Ho, .sup.175Yb, .sup.177Lu, .sup.186Re, .sup.188Re, .sup.213Bi and .sup.225Ac or with .sup.18F, .sup.131I or .sup.211At, and one or two biological targeting vectors which are coupled to the chelator or fluorinating group via one or more squaric acid groups.

The present disclosure provides phospholipid-containing compounds, pharmaceutical compositions and microspheres that exhibit high affinity for mineralized metals. The present disclosure also provides strategies for using said compounds, compositions and microspheres in the treatment of nephrolithiasis or kidney stone disease, and methods of manufacturing and preparing said compounds and compositions.

Described herein are methods and compositions relating to the treatment of e.g., cancer, autoimmune disease, immune deficiency, and/or neurodegenerative disease. In some embodiments, the methods of treatment relate to administering a compound as described herein. In some embodiments, the subject treated according to the methods described herein is a subject determined to have an increased level of DNA damage.

The present invention relates to a new process for the preparation of the crystalline polymorph of sodium neridronate in form hemihydrate F, comprising the following steps: a) reacting the 6-aminohexanoic acid with a mixture of phosphorous acid and methanesulfonic acid at a temperature in the range from 60 to 80° C., under stirring, until a clear solution is obtained; b) adding phosphorus trichloride to said solution of step (a) under stirring at a temperature in the range of 60 to 80° C.; c) diluting with water the reaction mixture obtained from the previous step (b) and heating said water diluted mixture at a temperature in the range from 80 to 120° C.; d) cooling the heated mixture obtained in step (c) up to room temperature, diluting it with water, then slowly adding an aqueous sodium hydroxide solution up to a pH in the range from 4.2 to 4.6, to obtain a neutralized solution; e) bringing the neutralized solution of step (d) up to a temperature of about 70° C., then subjecting it to a temperature increase in the range from 70 to 140° C., until evaporation of at least 70% of the initial volume of the neutralized solution of step (d), thus obtaining a suspension to be kept under stirring for at least 1 hour; f) cooling the suspension of step (e) up to a temperature in the range from around 5 to 25° C.; and g) recovering the crystalline sodium neridronate in hemihydrate form F by filtering the suspension of the previous step (f). The process is particularly simple, scalable and environmentally sustainable.

Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reducing resistance to the treatment, prevention, and diagnosis of diseases/symptoms induced by multiple myeloma. Embodiments include methods of treating a bone related disease, comprising the steps of: administering to a subject at least one therapeutically effective dose of a compound disclosed herein.

The disclosure provides a compound comprising bisphosphonate functional group and chelating agent. The bisphosphonate functional group part has high affinity for bone tissue, and the chelating agent part has high affinity for metal tracer such as radioisotope. The disclosed compound could be rapidly adsorbed onto the bone surface, and could steady emit ionizing radiation. Therefore, the disclosed compound is suitable for bone scanning technology to find abnormalities in bone.

Endosseous implant to be applied to a human or animal bone, wherein the surface of the implant is made from titanium or a titanium alloy, said implant having a smooth or rough surface texture, which is characterized in that said surface has been treated with at least one selected organic phosphonate compound or a pharmaceutically acceptable salt or ester or an amide thereof; process for producing said implants.

The present invention relates to a new process for the preparation of the crystalline polymorph of sodium neridronate in form hemihydrate F, comprising the following steps: a) reacting the 6-aminohexanoic acid with a mixture of phosphorous acid and methanesulfonic acid at a temperature in the range from 60 to 80° C., under stirring, until a clear solution is obtained; b) adding rl phosphorus trichloride to said solution of step (a) under stirring at a temperature in the range of 60 to 80° C.; c) diluting with water the reaction mixture obtained from the previous step (b) and heating said water diluted mixture at a temperature in the range from 80 to 120° C.; d) cooling the heated mixture obtained in step (c) up to room temperature, diluting it with water, then slowly adding an aqueous sodium hydroxide solution up to a pH in the range from 4.2 to 4.6, to obtain a neutralized solution; e) bringing the neutralized solution of step (d) up to a temperature of about 70° C., then subjecting it to a temperature increase in the range from 70 to 140° C., until evaporation of at least 70% of the initial volume of the neutralized solution of step (d), thus obtaining a suspension to be kept under stirring for at least 1 hour; f) cooling the suspension of step (e) up to a temperature in the range from around 5 to 25° C.; and g) recovering the crystalline sodium neridronate in hemihydrate form F by filtering the suspension of the previous step (f). The process is particularly simple, scalable and environmentally sustainable