Process for Producing EMD of Increased Stability

Patent metadata

Field	Value
Publication number	US-2016324728-A1
Application number	US-201515111847-A
Country	US
Kind code	A1
Filing date	Jan 19, 2015
Priority date	Jan 17, 2014
Publication date	Nov 10, 2016
Grant date	—

Abstract

The present invention relates to a process for producing a pharmaceutical, dental and/or cosmetic formulation comprising purified enamel matrix proteins and/or enamel matrix derivative (EMD) proteins, which is heat stable. In particular, the present invention is related to a process for producing stable formulations of enamel matrix proteins and/or enamel matrix derivative (EMD) proteins, wherein said proteins and/or derivatives are solved in a low pH formulation before being subjected to a heat-treatment step.

First claim

1 . A process for producing a pharmaceutical, dental and/or cosmetic formulation comprising enamel matrix proteins and/or enamel matrix derivative (EMD) proteins and a suitable pharmaceutical carrier, comprising the following steps:
a. isolating enamel matrix proteins and/or enamel matrix derivative (EMD) proteins from a developing mammal's teeth, b. solving said isolate in a suitable pharmaceutical carrier, c. lowering the pH of said formulation initially to below pH 4, and d. heating said formulation to between 40-100° C. for at least 10 minutes.

2 . A process according to claim 1 , wherein the pH of said formulation is in step c. is lowered to below 3.5.

3 . A process according to claim 1 , wherein step d. comprises heating said formulation to at least 80° C. for at least 3 hours.

4 . A process according to claim 1 , wherein step d comprises heating said formulation to at least 50° C. for at least 1 hour.

5 . A process according to claim 1 , wherein the suitable pharmaceutical carrier is a universal buffer.

6 . A process according to claim 3 , wherein the suitable pharmaceutical carrier is aqueous acetic acid, citric acid, or H 2 O.

7 . A process according to claim 1 , whereinthe enamel matrix proteins and/or enamel matrix derivative (EMD) proteins comprise at least 60-70% amelogenin, having an average molecular weight selected from the group consisting of between 18 and 25 kDa, between 20 and 24 kDa, between 20 and 22 kDa, and 20 kDa.

8 . A process according to claim 1 , which further comprises mixing the formulation of step d. with a suitable viscosity modifier.

9 . A process according to claim 6 , which further comprises adjusting the pH of the formulation of step d. to at least pH5 before mixing said formulation with a suitable viscosity modifier.

10 . A process according to claim 6 , wherein the viscosity modifier is PGA.

11 . A process according to claim 8 , wherein the PGA is e-beam sterilized PGA and wherein the formulation has a pH of at least pH5.

12 . A process according to claim 8 , wherein the PGA is sterilized propylene glycol alginate (PGA) with an weight average molecular weight above 130 kDa.

13 . A process according to claim 1 , which further comprises adjusting the pH of the formulation of step d. to at the most pH 5.

14 . A pharmaceutical, dental and/or cosmetic formulation comprising enamel matrix proteins and/or enamel matrix derivative (EMD) proteins and a suitable pharmaceutical carrier, wherein the pH of said formulation is between pH 2 and pH 5.

15 . A process according to claim 13 , wherein said formulation is mixed with a suitable viscosity modifier.

16 . A process according to claim 15 , wherein the viscosity modifier is hyaluronic acid.

17 . A process according to claim 16 , wherein the Hyaluronic acid is e-beam sterilized.

18 . A pharmaceutical, dental and/or cosmetic formulation comprising enamel matrix proteins and/or enamel matrix derivative (EMD) proteins and a suitable pharmaceutical carrier produced by a process according to claim 1 .

19 . A pharmaceutical, dental and/or cosmetic formulation comprising enamel matrix proteins and/or enamel matrix derivative (EMD) proteins and a suitable pharmaceutical carrier according to claim 18 , further comprising arginine.

20 . A pharmaceutical, dental and/or cosmetic formulation according to claim 19 , wherein said arginine is present in the formulation in a concentration of at the most 500 mM.

21 . A pharmaceutical, dental and/or cosmetic formulation according to claim 18 , which is characterized by a shelf life and/or durability of at least 12 months at 2° C.-RT.

22 . A pharmaceutical, dental and/or cosmetic formulation according to claim 18 , which is characterized by a shelf life and/or durability over a period of at least 12 months at RT.

23 . A pharmaceutical, dental and/or cosmetic formulation according to claim 18 , further comprising a suitable bone ceramic and/or a bonegraft.

24 . A pharmaceutical, dental and/or cosmetic formulation claim 18 , wherein the enamel matrix proteins and/or enamel matrix derivative (EMD) proteins are present in the formulation in a concentration of between 5-35 mg/ml.

25 . A pharmaceutical, dental and/or cosmetic formulation according to claim 24 , wherein the enamel matrix proteins and/or enamel matrix derivative (EMD) proteins are present in the formulation in a concentration of at least 29 mg/ml.

26 . A method of treatment comprising administering a pharmaceutical, dental and/or cosmetic formulation according to claim 18 to a patient in need of such treatment.

27 . A method according to claim 26 wherein the patient suffers from periimplant diseases and/or periodontitis.

28 . A kit comprising a pharmaceutical, dental and/or cosmetic formulation according to claim 18 , and at least one further component selected from the group consisting of granules, bone ceramics, scaffolds, a bonegraft, natural bone material, a bone block, artificial teeth, and an implant.

29 . A process according to claim 1 , wherein the pH of said formulation is in step c is lowered to 2.

Assignees

• Straumann Holding Ag

Inventors

• Apicella Alessandra
• Heunemann Peggy

Classifications

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61P1/02

  Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis · CPC title

• A61K6/56

  Apical treatment · CPC title

• A61K6/831

  comprising non-metallic elements or compounds thereof, e.g. carbon · CPC title

• A61K6/60

  comprising organic or organo-metallic additives · CPC title