FILLER COMPOSITION COMPRISING BETA-GLUCANS

• US 20130196944A1
• Filed: 08/17/2011
• Published: 08/01/2013
• Est. Priority Date: 08/19/2010
• Status: Abandoned Application

• Current Assignee: Merz Pharma GmbH & Company Kgaa
• Original Assignee: Merz Pharma GmbH & Company Kgaa
• Inventors: Barg, Heiko
• Application Number:
  US13/816,585
• Publication Number:
  US 20130196944A1
• Time in Patent Office: Days
• US Class Current: 514/54
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61K 8/73 Polysaccharides
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations

Abstract

The present invention pertains to a filler composition comprising β-glucan moieties and optionally a cosmetically and/or pharmaceutically acceptable carrier. It further relates to a filler composition, wherein the β-glucan moieties are cross-linked. in one embodiment of the instant invention the filler composition is a dermal filler. In one further embodiment of the present invention the filler composition is for the treatment of wrinkles and/or folds. In another embodiment of the instant invention the filler composition is for use in the treatment of a medical condition. The filler composition provided in the present invention may further comprise one or more active pharmaceutical ingredients. Further, the present invention pertains to a process for preparing the filler composition as claimed herein.

Claims

1-15. -15. (canceled)

16. A filler composition comprising β

-glucan moieties and, optionally, a cosmetically and/or pharmaceutically acceptable carrier, wherein the β

-glucan moieties are cross-linked, and wherein the cross-linked β

-glucan moieties form a monophasic gel.

17. The filler composition of claim 16, wherein the β

-glucan moieties are selected from the group consisting of branched and unbranched β

-glucan moieties, β

-(1,3)-glucan, β

-(1,4)-glucan, β

-(1,3)-(1,4)-glucan, β

-(1,3)-(1,6)-glucan and β

-(1,4)-(1,6)-glucan moieties.

18. The filler composition of claim 16, wherein the β

-glucan moieties are selected from the group consisting of cellulose, chitin, chitosan, curdlan, laminarin, chrysolaminarin, lentil pan, lichenin, plea ran, zymosan, schizophyllan, scieroglucan, β

-glucans extracted from grain, and any β

-glucans produced by biotechnological means.

19. The filler composition of claim 18, wherein the grain is oat or barley.

20. The filler composition of claim 16, wherein the β

-glucan moieties are cross-linked by moieties that are not photo- or redox-crosslinkable.

21. The filler composition of claim 16, wherein the cross-linked β

-glucan moieties are obtained by reacting β

-glucan moieties with a bifunctional cross-linking agent selected from divinyl sulfone (DVS), butanediol diglycidyl ether (BDDE), 1,2,7,8-diepoxyoctane (DEO), 1,2,3,4-diepoxybutane, and polyethylene glycol diglycidyl ether, or by reacting β

-glucan moieties with a multifunctional cross-linking agent.

22. The filler composition of claim 21 wherein the multifunctional cross-linking agent is polyethylene glycol epoxide.

23. The filler composition of claim 16, further comprising one or more active pharmaceutical ingredients selected from the group consisting of anesthetics, local anesthetics, analgesics, anti-microbials, anti-inflammatory drugs, growth factors, hormones, cosmeceuticals, vitamins, nutrients, stimulants, steroids, vasoconstrictors, anti-thrombotic agents, anti-coagulation agents, tranquilizers, muscle relaxants, antifungals, lipolytic agents, biorejunevation agents, anti-aging agents, anti-bacterial agents, anti-histaminic agents, healing supporting agents, anti-acne agents, moisturizing agents, tanning agents and anti-cellulite agents, wherein the one or more active pharmaceutical ingredients are linked to the β

-glucan moieties or a bifunctional cross-linking agent

24. The filler composition of claim 16, wherein the attendant cosmetically and/or pharmaceutically acceptable carrier is selected from the group consisting of high purity water, glycerol, phosphate buffered saline, carboxy-methylcellulose, hyaluronic acid, and mixtures thereof.

25. The filler composition of claim 16, further comprising one or more pharmaceutical excipients selected from antioxidants, viscosity enhancers/modifiers, hydrating agents, bulking substances, tonicity agents, preservatives, surface active agents, and mixtures thereof.

26. The filler composition of claim 16, wherein the concentration of the β

-glucan moieties is between about 0.1 and about 5.0 wt.-% for β

-glucans greater than 100 kDa based on the final total weight of filler composition, or is between about 0.1 and about 10.0 wt.-% for β

-glucans less than or equal to 100 kDa based on the final total weight of filler composition.

27. The filler composition of claim 16, wherein the β

-glucan moieties exhibit an average molecular weight of from about 1 kDa to about 3 mDa.

28. The filler composition of claim 16 for aesthetic purposes, as a dermal filler, for the treatment of wrinkles and/or folds, or for use in the treatment of a medical condition selected from lipoatrophy, gastroesophageal reflux disease (GERD), urine incontinence, vesico-ureteral reflux (VUR), a psychological condition caused by the appearance of an aesthetic deficiency, for use in plastic, cosmetic, dental or general surgery, in ophthalmology, in orthopedics, in preventing tissue adhesions, and in urology.

29. The filler composition of claim 16 which is an injectable filler composition.

30. A method for volume augmentation of tissue comprising injecting the filler composition of claim 16 into a human or animal subject.

31. A process for preparing the filler composition of claim 16, comprising the steps of:

(i) adding a crosslinking reagent to a concentrated non-crosslinked β

-glucan gel; and

(ii) combining an aqueous solution of β

-glucan moieties and a hydrophobic medium containing a water-in-oil emulsifier thereby forming an emulsion of droplets of the β

-glucan moieties and adding a cross-linking agent capable of cross-linking the β

-glucan moieties to the emulsion;

or

(iii) combining a solution of at least one β

-glucan moiety with an aqueous solution containing at least one cross-linking agent, wherein;

a. the pH of the aqueous solution containing at least one cross-linking agent is adjusted to a pH value of between about 6 and about 10;

b. the concentration of the cross-linking agent is between about 2.5 wt-% (w/w β

-glucan) and 30 wt-% (w/w β

-glucan), or between about 2.5 wt-% (w/w β

-glucan) and 15 wt-% (w/w β

-glucan);

c. the concentration of β

-glucan moieties is between about 0.1 and about 5.0 wt-% for β

-glucans greater than 100 kDa based on the final total weight of filler composition, or between about 0.1 and about 10.0 wt.-% for β

-glucans less than or equal to 100 kDa based on the final total weight of filler composition;

d. the viscosity of the solution of β

-glucan moieties is adjusted to a force of between about 15 N and about 50 N for pressing the solution of β

-glucan moieties through a 27G1/2 needle; and

/or

e. the aqueous solution containing the cross-linking agent optionally further comprises one or more active pharmaceutical ingredients selected from the group consisting of anesthetics, analgesics, anti-microbials, anti-inflammatory drugs, growth factors, hormones, cosmeceuticals, vitamins, nutrients, stimulants, steroids, vasoconstrictors, anti-thrombotic agents, anti-coagulation agents, tranquilizers, muscle relaxants, antifungals, lipolytic agents and biorejunevation agents.

32. The process of claim 31, herein the crosslinking agent is BODE.

33. A kit comprising the filler composition of claim 29 and an injection device, wherein the injection device is a syringe or an electronic injection device.

34. An injection device comprising the filler composition of claim 29.