Method of treating endo-osteal materials with a bisphosphonate solution

• US 5,733,564 A
• Filed: 09/19/1995
• Issued: 03/31/1998
• Est. Priority Date: 04/14/1993
• Status: Expired due to Term

• Current Assignee: Leiras Oy (Bayer AG)
• Original Assignee: Leiras Oy (Bayer AG)
• Inventors: Lehtinen, Risto Tapani
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US08/525,561
• Time in Patent Office: 924 Days
• Field of Search: 424/423, 623/16
• US Class Current: 424/423
• CPC Class Codes: A61F 2/0095 Packages or dispensers for prostheses or other implants for intraocular lenses A61F2/1691; for dental surgery A61C19/02
• CPC Class Codes: A61F 2/30 Joints
• CPC Class Codes: A61F 2002/3085 with a threaded, e.g. self-tapping, bone-engaging surface, e.g. external surface
• CPC Class Codes: A61F 2310/00023 Titanium or titanium-based alloys, e.g. Ti-Ni alloys
• CPC Class Codes: A61F 2310/00179 Ceramics or ceramic-like structures
• CPC Class Codes: A61F 2310/00796 Coating or prosthesis-covering structure made of a phosphorus-containing compound, e.g. hydroxy(l)apatite
• CPC Class Codes: A61L 2/18 Liquid substances or solutions comprising solids or dissolved gases
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/02 Inorganic materials

Abstract

An endo-osteal material which includes an endo-osteal material treated with a solution of a bisphosphonate of formula (1) wherein X is H, OH, Cl, F or a methyl group and Y is Cl, OH, --(CH₂)₂ --N(CH₃)--(CH₂)₄ --CH₃, --(CH₂)_n --CH₃ or --(CH₂)_n --NH₂, where n is zero or an integer being 1 to 8, --NHZ, where Z is pyridinyl or cycloheptyl, SZ'"'"', where Z'"'"' is pyridinyl or chlorosubstituted phenyl or Y is a pyridinylsubstituted lower alkyl chain; or a non-toxic, pharmaceutically acceptable salt or ester thereof dissolved in an appropriate solvent. ##STR1##

Claims

1. A method of treating endo-osteal materials which includes immersing the endo-osteal material in an aqueous solution comprising an effective amount of a bisphosphonate of the formula (I) ##STR4## wherein X is H, OH, Cl, F or a methyl group and Y is Cl, OH, --(CH₂)₂ --N(CH₃)--(CH₂)₄ --CH₃, --(CH₂)_n --CH₃ or --(CH₂)_n --NH₂, where n is zero or an integer being 1 to 8, --NHZ, where Z is pyridinyl or cycloheptyl, SZ'"'"', where Z'"'"' is pyridinyl or chlorosubstituted phenyl or Y is a pyridinylsubstituted lower alkyl chain;

or a non-toxic, pharmaceutically acceptable salt or ester thereof, after which the endo-osteal material is either

removed from the solution, dried and sterilized, or

sealed in a vessel, comprising a bisphosphonate solution and sterilized.

2. An endo-osteal material wherein said endo-osteal material is treated with a solution of a bisphosphonate of the formula (I) ##STR5## wherein X is H, OH, Cl, F or a methyl group and Y is Cl, OH, --(CH₂)₂ --N(CH₃)--(CH₂)₄ --CH₃, --(CH₂)_n --CH₃ or --(CH₂)_n --NH₂, where n is zero or an integer being 1 to 8, --NHZ, where Z is pyridinyl or cycloheptyl, SZ'"'"', where Z'"'"' is pyridinyl or chlorosubstituted phenyl or Y is a pyridinylsubstituted lower alkyl chain;

or a non-toxic, pharmaceutically acceptable salt or ester thereof dissolved in an appropriate solvent.

3. The endo-osteal material according to claim 2 wherein said endo-osteal material is placed in a closed vessel comprising a sterilized solution of a bisphosphonate of the formula (I) or a non-toxic, pharmaceutically acceptable salt or ester thereof dissolved in an appropriate solvent.

4. The endo-osteal material according to claim 2 or 3 wherein said endo-osteal material comprises a metal or metal alloy substrate.

5. The endo-osteal material according to claim 4 wherein said endo-osteal material comprises a substrate of titanium or a titanium based alloy said substrate being coated with a bone-binding layer.

6. The endo-osteal material according to claim 5 wherein said substrate is coated with a layer comprising hydroxyapatite.

7. A endo-osteal material according to claim 2 or 3 wherein said endo-osteal material is a ceramic or glass-ceramic prosthesis.

8. An endo-osteal material according to claim 2 or 3 wherein said bisphosphonate compound is selected from the group consisting of clodronate, pamidronate, etidronate, alendronic acid, neridronic acid, risedroic acid, tiludronate, the bisphosphonate of formula (I) wherein X is H and Y is cycloheptylamino, the bisphosphonate of formula (I) wherein X is OH and Y is --(CH₂)₂ --N(CH₃)--(CH₂)₄ --CH₃, and pharmaceutically acceptable salts and esters of said compounds.

9. The endo-osteal material according to claim 8 wherein said bisphosphonate compound is clodronate or its pharmaceutically acceptable salt or ester.

10. The endo-osteal material according to claim 9 wherein said bisphosphonate compound is clodronate disodium.

11. The endo-osteal material according to claim 9 wherein said bisphosphonate compound is clodronate disodium and the endo-osteal material is a dental implant comprising a substrate of titanium or a titanium based alloy said substrate being coated with a layer comprising hydroxyapatite.