# US 9,040,637 B2 · Manganese comprising nanostructures

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- Number: US 9,040,637 B2
- Document ID: US9040637B2
- Status: Granted
- Kind: B2
- Application number: 14/345,461
- Filed: 2012-09-20
- Published: 2014-11-27
- Granted: 2015-05-26
- Earliest claimed: 2011-09-23
- Assignees: Spago Imaging AB
- Applicants: Spago Imaging AB
- Inventors: Oskar Axelsson; Rodrigo M. Petoral, Jr.; Fredrik Ek; Petter Lauritzson
- Web page: https://patentgrep.com/patent/US9040637B2

## CPC

- A61K 51/065: {conjugates with carriers being macromolecules}
- A61K 49/12: Macromolecular compounds
- A61K 49/124: {dendrimers, dendrons, hyperbranched compounds}
- A61K 49/128: {comprising multiple complex or complex-forming groups, being either part of the linear polymeric backbone or being pending groups covalently linked to the linear polymeric backbone}
- A61K 49/1818: {particles, e.g. uncoated or non-functionalised microparticles or nanoparticles}
- A61K 49/1857: {the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- B82Y 15/00: Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
- C08G 73/0206: {Polyalkylene(poly)amines}
- C08G 73/0213: {Preparatory process}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS

## Abstract

Disclosed herein are nanostructures comprising a polymeric framework comprising at least five geminal bisphosphonate groups, wherein the geminal bisphosphonate groups independently of each other are incorporated as —R3R4C(P═O(OR1)(OR2))2, wherein R1 and R2 are independently selected from the group consisting of a negative charge, H, alkyl and aryl, and wherein at least one of R3 and R4 is a group connected to the polymeric framework with the proviso that when only one of R3 and R4 is such a connected group, the other of R3 and R4 is either a group being able to connect to the polymeric framework, or the residue of such a group, or selected from the group consisting of H, OH, OR5 and R5, wherein R5 is a lower alkyl. The polymeric framework may comprise manganese ions. Disclosed are also methods for producing such manganese containing nanostructures, compositions comprising such manganese containing nanostructures and use of such manganese containing nanostructures, i.a. as MRI contrasting agents.

## Claims

### Claim 1

A nanostructure comprising manganese ions incorporated in a polymeric framework comprising at least five geminal bisphosphonate groups, wherein the geminal bisphosphonate groups independently of each other are incorporated as
—R3R4C(P═O(OR1)(OR2))2
wherein:
R1 and R2 are independently selected from the group consisting of a negative charge, H, alkyl and aryl, and
at least one of R3 and R4 is a group connected to the polymeric framework, or forming part of the polymeric framework, with the proviso that when only one of R3 and R4 is such a connected group, the other of R3 and R4 is either a group being able to connect to the polymeric framework, or the residue of such a group, or selected from the group consisting of H, OH, OR5 and R5, wherein R5 is a lower alkyl.

### Claim 2 (depends on 1)

A nanostructure according to claim 1, wherein the group connected to the polymeric framework, and/or the group being able to connect to the polymeric framework or the residue of such a group is selected from the group consisting of:
(CH2)n Si(Rx)3 wherein Rx independently is a lower alkyl, OH, O−, or O—, — denotes a bond to the polymeric framework, and n is 1-5,
(CH2)nCORy wherein Ry is O—, NH2, NHRz, NRz2, or a bond to the polymeric framework, Rz is a lower alkyl and n is 1-5, and — denotes a bond to the polymeric framework, and
(CH2)nSO2Ry wherein Ry is O—, NH2, NHRz, NRz2, or a bond to the polymeric framework, Rz is a lower alkyl and n is 1-5 and — denotes a bond to the polymeric framework.

### Claim 3 (depends on 1)

A nanostructure according to claim 1, which comprises silicon atoms.

### Claim 4 (depends on 3)

A nanostructure according to claim 3, wherein the Si/Mn molar ratio is 5-20.

### Claim 5 (depends on 1)

A nanostructure according to claim 1, wherein R3 and/or R4 are/is selected from the group consisting of —(CH2)n—Si(Rx)3, wherein Rx independently is a lower alkyl, OH, O−, or O—, — denotes a bond to the polymeric framework, and n is 1-5.

### Claim 6 (depends on 1)

A nanostructure according to claim 1, wherein the hydrodynamic diameter of the nanostructures is 3-7 nm.

### Claim 7 (depends on 1)

A nanostructure according to claim 1, wherein the hydrodynamic diameter of the nanostructure is 10-20 nm.

### Claim 8 (depends on 1)

A nanostructure according to claim 1, wherein the polymeric framework comprises monomer residues containing a geminal bisphosphonate group and two organo-oxysilane groups.

### Claim 9 (depends on 1)

A nanostructure according to claim 1, wherein the polymeric framework is derived from polyethyleneimine.

### Claim 10 (depends on 1)

A nanostructure according to claim 1, wherein the P/Mn molar ratio is 7-20.

### Claim 11 (depends on 1)

A nanostructure according to claim 1, wherein said nanostructure further comprises hydrophilic groups attached to the outer parts.

### Claim 12 (depends on 11)

A nanostructure according to claim 11, wherein the hydrophilic groups comprise —(CH2CH2O)nCH3 moieties wherein n=4-50.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising a nanostructure according to claim 1.

### Claim 14 (depends on 13)

An MRI contrast agent comprising a pharmaceutical composition according to claim 13.

### Claim 15 (depends on 1)

A method for obtaining a nanostructure according to claim 1, comprising:
obtaining nanostructures of a polymeric framework comprising geminal bisphosphonates, and
contacting said nanostructures with manganese ions.

### Claim 16 (depends on 1)

An MRI contrast agent comprising a nanostructure according to claim 1.