Bisphosphonates vinylic monomers and polymers and uses thereof

Patent metadata

Field	Value
Publication number	US-9884880-B2
Application number	US-201314401964-A
Country	US
Kind code	B2
Filing date	May 20, 2013
Priority date	May 20, 2012
Publication date	Feb 6, 2018
Grant date	Feb 6, 2018

Abstract

The present invention provides novel bisphosphonates vinylic monomers, polymers and particles that have utility as biologically active molecule (such as drugs) carriers, medical device coatings and for imaging/radiology applications, especially in bone and dental applications. The invention also provides methods of synthesizing the monomers, polymerizing the polymers, and assembling the particles of the invention.

First claim

What is claimed is:

1. A compound or a polymer comprising formula I:

wherein
X is H, CH 3 , CN, phenyl, substituted phenyl, (CH 2 ) m Z, or phenyl(CH 2 ) m Z;
m equals 1 to 20;
n equals 1-200; and
Z is CN, NH 2 , Thiol, OH, or CO 2 H.

2. A particle comprising the compound of formula 1.

3. The particle of claim 2 , further comprising a biologically active molecule.

4. A particle comprising a metallic core or a metallic oxide core bound via a reactive group to the compound of formula 1.

5. The polymer of claim 1 , wherein said polymer is water soluble.

6. An article, comprising a biocompatible or a plastic core coated with the polymer of claim 1 .

7. A method of making the particle of claim 2 , comprising the step of free radical homopolymerization or copolymerization of monomers of the compound of formula 1 in the presence of:
(a) a free radical homopolymerization or copolymerization initiator; and
(b) a free radical homopolymerization or copolymerization stabilizer, thereby making the particle of claim 2 .

8. The method of claim 7 , comprising a reaction mixture for said making the particle, wherein said reaction mixture comprises: 1-20% by weight of monomers of the compound of formula 1; 0.2-50% by weight of a free radical homopolymerization or copolymerization initiator; and 0.1-20% by weight of a free radical homopolymerization or copolymerization stabilizer.

9. A method of making the particle of claim 4 , comprising a Michael addition reaction including:
(a) thiolating a double bond within the compound of formula 1; and
(b) binding the thiolated compound of formula 1 to said amino group within said biologically active molecule.

10. The method of claim 9 , wherein said thiolating is by reacting a compound of formula 1 with 1, 2-amino-thio-ethanol.

11. A method of imaging a bone in a subject, comprising the steps of:
(a) administering to said subject a composition comprising an effective amount of the particle of claim 2 comprising a dye; and
(b) irradiating said dye;
thereby imaging a bone in a subject.

12. The method of claim 11 , wherein said dye is covalently bound to said compound of formula 1.

13. The method of claim 11 , wherein said dye is physically entrapped within said particle.

14. A method of delivering a biologically active compound to a bone in a subject, comprising the step of administering to said subject a composition comprising an effective amount of the particle of claim 3 , thereby delivering a biologically active compound to a bone in a subject.

15. A method of treating a bone related disease in a subject, comprising the step of administering to said subject a composition comprising an effective amount of the particle of claim 3 , said particle of claim 3 comprises a bone related disease drug, thereby treating a bone related disease in a subject.

Assignees

• Univ Bar Ilan

Inventors

• Margel Shlomo
• Mizrahi Dana
• Gluz Eran
• Chen Ravit

Classifications

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61K47/6933

  the polymer being obtained by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol · CPC title

• C07F9/386

  containing hydroxy substituents in the hydrocarbon radicals · CPC title

• C07F9/3873 Primary

  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) · CPC title

• A61K2123/00

  Preparations for testing in vivo · CPC title