EMD formulation comprising PGA

Patent metadata

Field	Value
Publication number	US-9789190-B2
Application number	US-201113643658-A
Country	US
Kind code	B2
Filing date	Oct 17, 2011
Priority date	Oct 15, 2010
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

Enamel Matrix Derivative (EMD) proteins and enamel matrix proteins are widely used in clinical dentistry because of their ability to promote regeneration of soft and hard tissues and to reduce inflammation and infections. The present invention relates to the surprising finding that a pharmaceutical, dental and/or cosmetic formulation, which comprises purified Enamel Matrix Derivative (EMD) proteins and/or enamel matrix proteins and sterilized Propylene Glycol Alginate (PGA), wherein the sterilized PGA is obtained from non-sterilized PGA having a weight average molecular weight (M wo ) of between 250-500 kDa, is more stable over time, especially, the pH is more stable over time.

First claim

The invention claimed is:

1. A pharmaceutical, dental and/or cosmetic formulation comprising enamel matrix proteins and/or enamel matrix derivative (EMD) proteins and a sterilized propylene glycol alginate, wherein said formulation comprises no more than 6 weight/volume % (w/v %) sterilized propylene glycol alginate (PGA), wherein the weight average molecular weight (Mw) of the PGA prior to sterilization is at least 250 kDa, and wherein said sterilized PGA has a weight average molecular weight (Mw) above 130 kDa.

2. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein the weight average molecular weight (Mw) of the sterilized PGA is in the range of between 130-250 kDa.

3. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , comprising sterilized PGA in the range of 3 weight/volume % (w/v %) to 6 w/v % with a weight average molecular weight above 130 kDa.

4. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein the weight average molecular weight (Mw) of the sterilized PGA is above or equal to 185 kDa.

5. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein the sterilized PGA is obtained from e-beam sterilization of non-sterilized PGA with an initial weight average molecular weight (Mwo) of at least 250 kDa.

6. A pharmaceutical, dental and/or cosmetic formulation according to claim 5 , wherein the sterilized PGA is obtained from e-beam sterilization of non-sterilized PGA with an initial weight average molecular weight (Mwo) in the range of 250 to 500 kDa.

7. A pharmaceutical, dental and/or cosmetic formulation according to claim 5 , wherein the applied e-beam sterilization dose is selected from a dose in the range of 25 to 30 kGy.

8. A pharmaceutical, dental and/or cosmetic formulation according to any claim 1 , wherein the 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.

9. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein said formulation has a pH above 3.5 over a period of at least 18 months.

10. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein said formulation has a pH above 3.5 at a temperature range of 2 to 8° C.

11. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein the formulation further comprises one or more pharmaceutically acceptable excipient(s), pharmaceutically acceptable carrier(s), or a combination thereof.

12. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein the amount of the enamel matrix proteins and/or enamel matrix derivative (EMD) proteins is in the range of 93% to about 98%, by weight/volume, based on the total combined weight of the matrix proteins and/or enamel matrix derivative (EMD) proteins and the sterilized PGA, not including other excipients.

13. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , additionally comprising one or more non-enamel matrix proteins and/or enamel matrix derivative (EMD) proteins active agents.

14. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , comprising at least two surface stabilizers.

15. A pharmaceutical, dental and/or cosmetic formulation according to claim 14 , wherein the surface stabilizer is selected from the group consisting of anionic surface stabilizer, cationic surface stabilizer, zwitterionic surface stabilizer and ionic surface stabilizer.

16. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , for use in medicine.

17. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , wherein the formulation is formulated for administration selected from the group consisting of oral, pulmonary, rectal, opthalmic, colonic, parenteral, intracisternal, intravaginal, intraperitoneal, local, buccal, nasal, and topical administration.

18. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 , formulated into a dosage form selected from the group consisting of liquid dispersions, oral suspensions, gels, aerosols, ointments, creams, controlled release formulations, fast melt formulations, lyophilized formulations, tablets, capsules, delayed release formulations, extended release formulations, pulsatile release formulations, and mixed immediate release and controlled release formulations.

19. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 for use in promoting and/or inducing regeneration of hard tissue, tissue mineralization, bone growth and/or bone regrowth, regeneration of dentin, cementogenesis, and/or binding between parts of living mineralized tissue, for bonding of a piece of living mineralized tissue to a bonding site on a piece of other living tissue, for endorsing binding between hard tissues, and/or for filling a mineralized wound cavity and/or tissue defect following from a procedure and/or trauma.

20. A pharmaceutical, dental and/or cosmetic formulation according to claim 1 for use in promoting and/or inducing regeneration of soft tissue and/or for treating and/or preventing an inflammation and/or infection and/or for treating SIRS, for promoting and/or inducing regeneration of hard tissue, tissue mineralization, bone growth and/or bone regrowth, regeneration of dentin, cementogenesis, and/or binding between parts of living mineralized tissue, for bonding of a piece of living mineralized tissue to a bonding site on a piece of other living tissue, for endorsing binding between hard tissues, and/or for filling a mineralized wound cavity and/or tissue defect following from a procedure and/or trauma.

21. A method comprising administering to a patient a therapeutic amount of the formulation of claim 1 .

22. The method according to claim 21 , further comprising the following steps:
a. isolating enamel matrix proteins and/or enamel matrix derivative (EMD) proteins from a developing mammal's teeth,
b. e-beam sterilizing non-sterilized PGA with an initial weight average molecular weight (Mwo) above 250 kDa with a dose in the range of 25 to 30 kGy, and
c. mixing the product obtained from a. and the product obtained from b.

23. A pharmaceutical, dental and/or cosmetic formulation, comprising enamel matrix proteins and/or enamel matrix derivative (EMD) proteins and sterilized propylene glycol alginate (PGA) with a weight average molecular weight above 130 kDa, wherein said formulation is produced by a process comprising the following steps:
a. isolating enamel matrix proteins and/or enamel matrix derivative (EMD) proteins from a developing mammal's teeth,
b. e-beam sterilizing non-sterilized PGA with an initial weight average molecular weight (Mwo) in the range of 250 to 500 kDa with a dose in the range of 25 to 30 kGy, and
c. mixing the product obtained from a. and the product obtained from b.

Assignees

• Garamszegi Laszlo
• Vital Andri
• Straumann Holding Ag

Inventors

• Garamszegi Laszlo
• Vital Andri

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61P1/02

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

• A61K6/54

  Filling; Sealing · CPC title