PHARMACEUTICAL COMPOSITIONS BASED ON A MICROEMULSION

• US 20100034880A1
• Filed: 02/05/2008
• Published: 02/11/2010
• Est. Priority Date: 02/08/2007
• Status: Abandoned Application

• Current Assignee: Nanoderma, Ltd.
• Original Assignee: Nanoderma, Ltd.
• Inventors: Levy, Haim, Sintov, Amnon
• Application Number:
  US12/525,811
• Publication Number:
  US 20100034880A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

The invention provides a transdermal, transmucosal pharmaceutical composition suitable for substantially extra-vascular application of at least one biologically active substance to biological membranes of a mammal, comprising a pharmaceutical or cosmetic composition comprising propylene carbonate at least one oil or source of fatty acid or surfactant; and water; in combination with the at least one biologically active substance wherein the propylene carbonate is adapted to enhance the bioavailability of the at least one biologically active substance.

Claims

1. A transdermal, transmucosal pharmaceutical composition suitable for substantially extra-vascular application of at least one biologically active substance to biological membranes of a mammal, comprising:

pharmaceutical or cosmetic composition comprising;

propylene carbonate;

at least one oil or source of fatty acid or surfactant; and

water;

in combination with the at least one biologically active substance;

wherein the propylene carbonate is adapted to enhance the bioavailability of said at least one biologically active substance.

2. A pharmaceutical composition according to claim 1, wherein the composition is a microemulsion or a nano-sized emulsion.

3. A pharmaceutical composition according to claim 1, wherein the propylene carbonate is water-miscible.

4. A pharmaceutical composition according to claim 1, wherein the propylene carbonate is in a concentration of 0.001% to 99% weight/weight.

5. A pharmaceutical composition according to claim 1, wherein the at least one oil is selected from the group consisting of alkyl, dialkyl, trialkyl, acyl, diacyl, triacyl, monoglycerides, diglycerides and triglycerides of mono- di- or tri-carboxylic acids selected from the group consisting of saturated mono- di- or tri-carboxylic acids and mono- or di- or tri-carboxylic acids containing ethylenic unsaturation.

6. A pharmaceutical composition according to claim 1, wherein the at least one oil or source of fatty acid is selected from amides, ethoxylated fats, mineral oil, petrolatum, vegetable oil, animal fats, and polyols.

7. A pharmaceutical composition according to claim 1, wherein the at least one oil or source of fatty acid is selected from isopropyl palmitate, isopropyl myristate, diethyl sebacate, diisopropyl adipate, cetyl oleate, oleyl alcohol, hexadecyl stearate, hexadecyl alcohol, caprylic triglycerides, capric triglycerides, isostearic triglycerides, adipic triglycerides, medium chain triglycerides (C8-C10 fatty acids), PEG-6-olive oil (Labrafil), propylene glycol myristyl acetate, lanolin oil, polybutene, wheatgerm oil, vegetable oils such as castor oil, corn oil, cottonseed oil, olive oil, palm oil, coconut oil, canola oil, sunflower oil, jojoba oil, peanut oil, hydrogenated vegetable oils, etc., and mineral oil.

8. A pharmaceutical composition according to claim 1, further comprising at least one muco-adhesive.

9. A pharmaceutical composition according to claim 8, wherein the at least one muco-adhesive is selected from acrylic polymers, polysaccharides, cellulose derivatives, cationized polymers, proteins, glycoproteins, and lectins.

10. A pharmaceutical composition according to claim 1, further comprising at least one gelling agent.

11. A pharmaceutical micro-emulsion composition according to claim 10, wherein the at least one gelling agent is selected from cationized guar gum, cellulose derivatives, acrylic polymers, polysaccharides, lipids, proteins, and polyhydroxy compounds.

12. A pharmaceutical composition according to claim 1, wherein the at least one gelling agent is present in a concentration of 0.01% to 50%.

13. A pharmaceutical composition according to claim 1, wherein the at least one surfactant is in a concentration of 0.1% to 90% wt./wt.

14. A pharmaceutical composition according to claim 13, wherein the at least one surfactant is selected from ionic or non-ionic surfactants.

15. A pharmaceutical composition according to claim 13, wherein the at least one surfactant is selected from bile salts and their derivatives thereof.

16. A pharmaceutical composition according to claim 13, wherein the at least one surfactant is selected from lecithin, lysolecithins, various phospholipids (e.g., phosphatidylcholine), oleic acid, and its derivatives thereof, fusidic acid and its derivatives thereof, polyoxyethylene alcohol ethers, polyoxyethylene sorbitan derivatives (polysorbates, e.g., Tweens such as Tween 20, 40, 60, 80, 85, etc.), sorbitan esters of fatty acids (e.g, sorbitan sesquioleate, sorbitan isostearate, sorbitan monolaurate, sorbitan monostearate, sorbitan monooleate, etc.), sugar esters (e.g., Sisterna sucrose esters, which are based on sucrose and vegetable fatty acids), capryloylcaproyl macrogol-8-glycerides (Labrasol), gelatine, albumin, starch, polyvinylpyrrolidone, polyvinyl alcohol, cetostearyl alcohol, glyceryl monoesters of fatty acids (e.g., glyceryl monostearate, glyceryl monooleate, glyceryl dioleate, etc.), polyglyceryl-6-dioleate (Plurol oleique), polyoxyethyleneglycol derivatives of fatty acids (e.g., Myrj 45, 49, 51, 52, 52S, 53, 59 etc.), polyoxyethyleneglycol ethers (e.g., polyoxyethylene (23) dodecyl ether or Brij 35 etc.).

17. A pharmaceutical composition according to claim 1, wherein the at least one biologically active substance is selected from an antibiotic, a polypeptide, a hormone, a protein-based drug, an anticancer an antiviral agent, a neurologically effective drug, an anti-emetic, an antihistamine, an anti-inflammatory agent, an anti-cholinergic drug an anti-hypertensive agent, an anti-angina drug, a narcotic analgesic, a narcotic antagonist, a blood factor, a bone metabolism agent, a prostaglandin, a protease inhibitor, an anti-parkinsonian drug, a combination of any of said biologically active substances or biologically active fragments or derivatives thereof.

18. A pharmaceutical composition according to claim 17, wherein the at least one biologically active substance is insulin.

19. A pharmaceutical composition according to claim 1, further comprising a pharmaceutically acceptable carrier.

20-33. -33. (canceled)

34. A method for forming a transdermal, transmucosal pharmaceutical micro-emulsion composition suitable for substantially external application of at least one biologically active substance to biological membranes of a mammal, the method comprising:

admixing propylene carbonate, at least one oil or source of fatty acid, or at least one surfactant and water to form a micro-emulsion; and

adding the at least one biologically active substance to the micro-emulsion such that the propylene carbonate enhances the bioavailability of said at least one biologically active substance.

35-43. -43. (canceled)