Bisphosphonates vinylic monomers and polymers and uses thereof

Patent metadata

Field	Value
Publication number	US-10508126-B2
Application number	US-201815888496-A
Country	US
Kind code	B2
Filing date	Feb 5, 2018
Priority date	May 20, 2012
Publication date	Dec 17, 2019
Grant date	Dec 17, 2019

Abstract

A compound or a polymer is claimed. A first formula can be

wherein X is H, CH 3 , CN, phenyl, substituted phenyl, (CH 2 ) m Z, or phenyl(CH 2 ) m Z; T is O, N, S or NH; m equals 1 to 20; n equals 1-100; and Z is CN, NH 2 , Thiol, OH, or CO 2 H. The second formula is:

wherein X is H, CH 3 , CN, phenyl, substituted phenyl, (CH 2 ) m Z, or phenyl(CH 2 ) m Z; and Z is CN, NH 2 , Thiol, OH, or CO 2 H. The third formula is

wherein: R 1 , R 2 , R 3 , and R 4 are independently: H, CH 3 , OH, or a halogen.

First claim

What is claimed is:

1. A particle comprising a compound or a polymer comprising a formula selected from the group consisting of:

wherein X is H, CH 3 , CN, phenyl, substituted phenyl, (CH 2 ) m Z, or phenyl(CH 2 ) m Z;
T is O, S or NH;
m equals 1 to 20;
n equals 1-100; and
Z is CN, NH 2 , Thiol, OH, or CO 2 H;

wherein X is H, CH 3 , CN, phenyl, substituted phenyl, (CH 2 ) m Z, or phenyl(CH 2 ) m Z; and
Z is CN, NH 2 , Thiol, OH, or CO 2 H;
or

wherein:
R 1 , R 2 , R 3 , and R 4 are independently: H, CH 3 , OH, or a halogen; and
wherein said particle has a particle size ranging from 40 nm to 2.2 μm.

2. The particle of claim 1 , further comprising a biologically active molecule.

3. The particle of claim 1 , wherein said compound or polymer is bound to a metallic core or a metallic oxide core via a reactive group.

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

5. An article comprising a biocompatible or a plastic core coated with the particle of any one of claims 1 and 2 - 4 .

6. A method of making the particle of claim 1 , comprising the step of free radical homopolymerization or copolymerization of monomers of the compound of (i) to (iii), 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 1 .

7. The method of claim 6 , wherein said making the particle is obtained in a reaction mixture, wherein said reaction mixture comprises:
1-20% by weight of said monomers;
0.2-50% by weight of said free radical homopolymerization or copolymerization initiator; and
0.1-20% by weight of said free radical homopolymerization or copolymerization stabilizer.

8. A method of making the particle of claim 7 , comprising a Michael addition reaction including:
(a) thiolating a double bond within the compound or the polymer; and
(b) binding the thiolated compound or polymer to an amino group within said biologically active molecule.

9. The method of claim 8 , wherein said thiolating is obtained by 1,2-amino-thio-ethanol.

10. 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 1 comprising a dye; and
(b) irradiating said dye;
thereby imaging a bone in a subject.

11. The method of claim 10 , wherein said dye is covalently bound to said particle.

12. The method of claim 10 , wherein said dye is physically entrapped within said particle.

13. 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 2 , thereby delivering a biologically active compound to a bone in a subject.

14. 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 2 , said particle of claim 2 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

• A61K49/0034

  Indocyanine green, i.e. ICG, cardiogreen · CPC title

• A61K31/80

  Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795 · CPC title

• A61K49/0054

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title