Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses

• US 8,709,385 B2
• Filed: 07/14/2010
• Issued: 04/29/2014
• Est. Priority Date: 01/14/2008
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Besonov, Alex, Berman, Tal, Schuz, David, Gazal, Elana
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US12/836,444
• Publication Number:
  US 20110008266A1
• Time in Patent Office: 1,385 Days
• Field of Search: 424/43, 424/45, 424/78.05, 424/78.07, 514/859, 514/861, 514/871, 514/944, 514/945
• US Class Current: 424/43
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• CPC Class Codes: A61K 8/90 Block copolymers A61K8/89 takes precedence
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

Pharmaceutical or cosmetic compositions and methods for their use are provided comprising water and a surfactant polymer system comprising a Poloxamer at a concentration of about 0.1% to about 15% by weight; wherein when the Poloxamer is between about 0.1% to about 5% Poloxamer. The composition can further comprise a supporting agent comprising a non-ionic surface active agent or a supporting agent comprising a non surfactant polymer or polysaccharide and an active agent, where the Poloxamer is capable of fixing the composition on delivery to a body surface. There are further provided therapeutic cell compositions and their uses.

Claims

1. A pharmaceutical or cosmetic composition comprising:

a. water;

b. at least two poloxamers at a concentration of about 0.1% to about 5% by weight of the composition;

c. one or more active agents,

wherein the composition is pressurized with a liquefied or compressed propellant;

wherein the weight ratio of the composition to the propellant is about 100;

5 to about 100;

25;

wherein the at least two poloxamers are a synergistic combination of at least one liquid poloxamer and at least one solid poloxamer; and

wherein the one or more active agents are soluble in the composition.

2. The composition of claim 1, wherein the poloxamers are selected from the group consisting of poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, and mixtures of two or more thereof.

3. The composition of claim 1, wherein the composition is capable of affording a fixing effect on application to a body surface at 30°

C. or more.

4. The composition of claim 1, wherein the at least two poloxamers are at a total amount of about 0.2% to about 2% by weight of the composition.

5. The composition of claim 1, wherein at least one of the two poloxamers comprises a molecular weight in a range (i) between about 2,000 and about 2,400;

or (ii) between about 6,800 and about 8,900;

or (iii) between about 7,600 and about 9,500;

or (iv) between about 9,800 and about 14,600;

or (v) between about 12,000 and about 18,000.

6. The composition of claim 1, further comprising a non-ionic surface active agent, wherein the ratio of the at least two poloxamers to non-ionic surface active agent is selected from about 1:

2;

about 1;

1;

about 2;

1;

about 4;

1;

about 8;

1;

about 10;

1;

about 15;

1;

about 20;

1;

about 30;

1;

about 40;

1 to about 50;

1;

from about 1;

2 to about 50;

1;

from about 1;

1 to about 1;

50;

from about 2;

1 to about 50;

1;

from about 4;

1 to about 50;

1;

from about 8;

1 to about 50;

1;

from about 10;

1 to about 50;

1;

from about 15;

1 to about 50;

1;

from about 20;

1 to about 50;

1;

from about 30;

1 to about 50;

1;

from about 40;

1 to about 50;

1;

from about 1;

2 to about 1;

1;

from about 1;

2 to about 2;

1;

from about 10;

1 to about 50;

1; and

from about 2;

1 to about 8;

10.

7. The composition of claim 1, further comprising a polymer or a polysaccharide, wherein the ratio of the at least two poloxamers to polymer or polysaccharide is selected from about 1:

1;

about 2;

1;

about 4;

1;

about 8;

1;

about 10;

1;

about 15;

1;

about 20;

1;

about 30;

1;

about 40;

1 to about 50;

1 from 1;

1 to about 50;

1;

from about 1;

2 to about 50;

1;

from about 1;

1 to about 1;

50;

from about 2;

1 to about 50;

1;

from about 4;

1 to about 50;

1;

from about 8;

1 to about 50;

1;

from about 10;

1 to about 50;

1;

from about 15;

1 to about 50;

1;

from about 20;

1 to about 50;

1;

from about 30;

1 to about 50;

1;

from about 40;

1 to about 50;

1;

from about 1;

2 to about 1;

1;

from about 10;

1 to about 50;

1;

from about 2;

1 to about 8;

10.

8. The composition of claim 1, wherein the viscosity of the composition at about body temperature is greater than the viscosity of the composition at room temperature.

9. The composition of claim 1, wherein the percentage by weight of the composition of polyoxyethylene component of the at least two poloxamers is between about 70% and about 85% of at least one of the two poloxamers.

10. The composition of claim 1, wherein a foam produced from the composition has a mild cooling effect or sensation.

11. The composition of claim 1, wherein the intradermal penetration of the active agent is in excess of about 300 micrograms/cm²/24 hr;

or wherein the at least two poloxamers improve the absorption of the active agent into the stratum corneum and thereafter into the dermis without an increase in transdermal penetration.

12. The composition of claim 1, wherein the at least two poloxamers are included in the composition in an amount sufficient to dissolve an active agent in an aqueous phase, wherein such an active agent is not fully soluble in said aqueous phase, or wherein the active agent is not otherwise fully soluble in water, in hydrophobic solvent, or in an oil phase of an emulsion and the at least two poloxamers are present in the composition in an amount sufficient to solubilize the active agent in the composition;

and wherein the active agent comprises at least one of diclofenac, salicylic acid, clindamycin or mixtures of two or more thereof.

13. The composition of claim 1, wherein the active agent in an effective amount is capable of causing the composition to form a gel, which in the presence of a sub-effective amount would be liquid.

14. The composition of claim 13, wherein the gelling effect is a result of a reduction in pH.

15. The composition of claim 1, further comprising at least one ingredient, comprising:

a. about 1% to about 50% by weight of the composition of a hydrophobic solvent;

b. about 1% to about 50% by weight of the composition of a non-volatile hydrophilic solvent;

c. a foam adjuvant;

or

d. about 1% to about 10% by weight of the composition of a volatile hydrophilic solvent;

or mixtures of two or more thereof;

wherein the foam adjuvant comprises a fatty alcohol having 15 or more carbons in their carbon chain;

or a fatty acid having 16 or more carbons in its carbon chain;

or a fatty alcohol, derived from beeswax and including a mixture of alcohols, a majority of which have at least 20 carbon atoms in their carbon chains;

or a fatty alcohol having at least one double bond;

or a fatty acid having at least one double bond;

or a branched fatty alcohol;

or a branched fatty acid or a fatty acid substituted with a hydroxyl group;

or a mixture of two or more thereof.

16. The composition of claim 15, wherein the composition is an oil in water emulsion.

17. The composition according to claim 1, further comprising a polymeric agent or a polysaccharide, wherein the at least two poloxamers and the polymeric agent or polysaccharide when present together act synergistically so that the amount of the at least two poloxamers required can be reduced.

18. The composition according to claim 1, further comprising a polymeric agent or a polysaccharide, wherein the polymeric agent or polysaccharide is water soluble or water dispersible.

19. The composition according to claim 1, wherein the composition comprises about 95% or more than 95% by weight of the composition of water.

20. The composition according to claim 18, wherein said at least one water-soluble or water dispersible polymeric agent or polysaccharide comprises one or more of an acrylic acid polymer, an acrylate/C10-30 alkyl acrylate crosspolymer, a carbomer, a methocel, a sodium carboxymethylcellulose, a polyvinylpyrrolidone, a xanthan gum or a mixture of two or more thereof.

27. A method of treating or alleviating a disorder of a mammalian subject in need thereof, comprising administering a gel or foam produced from the composition of claim 12 to an area of skin or mucosa of said mammalian subject having said disorder, wherein the disorder is selected from the group consisting of one or more of pain, dermatological inflammation, acne, dermatitis, bacterial skin infections, cellulitis, cutaneous abscesses, folliculitis, furuncles, impetigo, warts, eczema, keratosis, and skin ulcers.

28. The composition of claim 1, wherein the composition is administered as a gel or a foam.

30. The composition of claim 1, wherein the one or more active agents are encapsulated in microspheres.

31. The composition of claim 13, wherein the gelling effect is a result of an increase of ionic strength.

21. A pharmaceutical or cosmetic foamable composition for application to a delivery site in a subject, the composition comprising:

A. a carrier comprising;

a. about 5% to about 20% by weight of the carrier of at least two poloxamers;

b. water;

c. about 0.2% to about 15% by weight of the carrier of at least one hydrophobic solvent;

d. about 0.5% to about 5% by weight of the carrier of at least one surfactant;

e. about 0.5% to about 15% by weight of the carrier of at least one hydrophilic solvent;

f. one or more active agents, which optionally may be encapsulated; and

B. a propellant,

wherein the composition is stored in an aerosol container and upon release expands to form a breakable short term stable foam;

wherein the weight ratio of the carrier to the propellant is about 100;

5 to about 100;

25;

wherein the at least two poloxamers are a synergistic combination of at least one liquid poloxamer and at least one solid poloxamer; and

wherein the one or more active agents are soluble in the composition.

22. The composition of claim 21, wherein the at least one hydrophobic solvent comprises at least one silicone compound.

23. The composition according to claim 22, wherein said at least one silicone compound comprises one or more of a cyclomethicone, a dimethicone, or a cyclomethicone and a dimethicone copolyol.

24. The composition of claim 22, further comprising an oil.

25. The composition of claim 21, wherein the hydrophilic solvent comprises a glycol, glycerin, or mixtures thereof.

26. The composition of claim 25, wherein the hydrophilic solvent comprises a glycol and glycerin, and the intradermal penetration of the active agent is in excess of about 300 micrograms/cm²/24 hr;

or wherein the at least two poloxamers improve the absorption of the active agent into the stratum corneum and thereafter into the dermis without an increase in transdermal penetration.

29. A pharmaceutical or cosmetic composition comprising either:

A.

a. water;

b. at least two poloxamers at a concentration of about 0.1% to about 15% by weight of the composition;

B.

a. about 5% to about 20% by weight of the composition of at least two poloxamers;

b. about 79% to about 93.8% of the composition of water;

c. about 0.2% to about 15% by weight of the composition of at least one hydrophobic solvent;

d. about 0.5% to about 5% by weight of the composition of at least one surfactant; and

e. about 0.5% to about 15% by weight of the composition of at least one hydrophilic solvent;

or

C.

a. about 1% to about 20% by weight of the composition of at least two poloxamers;

b. 0% to about 5% by weight of the composition of at least one polymeric agent;

c. about 79% to about 99% of the composition of water;

d. 0% to about 5% by weight of the composition of at least one silicone; and

e. 0% to about 5% by weight of the composition of at least one surfactant;

wherein A, B or C are pressurized with a liquefied or compressed propellant;

wherein the weight ratio of the composition to the propellant is about 100;

5 to about 100;

25; and

wherein the at least two poloxamers are a synergistic combination of at least one liquid poloxamer and at least one solid poloxamer.