Liquid Compositions Capable of Foaming and Including Active Agents, and Methods for Making or Developing Same

• US 20110059117A1
• Filed: 07/19/2010
• Published: 03/10/2011
• Est. Priority Date: 07/24/2009
• Status: Active Grant

• Current Assignee: MIKA Pharma GmbH (Giuliani Group SA)
• Original Assignee: MIKA Pharma GmbH (Giuliani Group SA)
• Inventors: Seigfried, Bernd G.
• Granted Patent: US 9,005,626 B2
• Time in Patent Office: Days
• US Class Current: 424/184.1
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• 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 31/4174 Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• 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 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/10 Expectorants
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 23/00 : Anaesthetics
• CPC Class Codes: A61P 23/02 : Local anaesthetics
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• 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 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/02 : Local antiseptics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

A liquid composition suitable for topical use comprising is provided that includes a phospholipid foaming agent and at least one solvent; and a pharmaceutically acceptable active agent; wherein the liquid composition is capable of mechanically foaming without an additional propellant; and wherein upon mechanical foaming of 250 ml of the liquid composition results in a foam with a foam volume of at least about 400 ml and a foam stability wherein at least about 50% of the foam volume is still present after about 5 minutes at 25° C., as determined using a SITA foam measurement. Also provided herein are methods of making disclosed compositions and methods of use.

Claims

1. A method for making a foamable liquid composition for topical use, comprising:

a. providing a liquid composition comprising at least one pharmaceutically active agent, at least one solvent, and at least one foaming agent;

b. mechanically creating a foam of the liquid composition;

c. scanning the foam surface to determine the stability and the volume of the foam;

d. varying the concentration of at least one of the pharmaceutically active agent, the solvent, or the foaming agent;

e. repeating steps b and c until 250 ml of the liquid composition, after the mechanical creation of the foam, has a foam volume of at least 400 ml and a foam stability wherein at least about 50% of the foam volume is still present after about 5 minutes at 25°

C.

3. The method of claim 1, further comprising producing a correlation between the foam as specified by the SITA measurement method and the pharmaceutical properties.

4. The method of claim 1, wherein a foam applicator-is selected for the mechanical foaming of the liquid composition, a foam is created from the liquid composition by the selected foam applicator, and a correlation is produced between the properties, especially the pharmaceutical properties of the foam created via the foam applicator and the foam volume and/or the foam stability as determined via the SITA measurement method.

5. The method of claim 1, wherein the characterized in that such a foam is created from the liquid composition that possess foam density densities of the foam are is between 0.05 g/ml and 0.8 g/ml, as measured by the SITA foam measurement method.

6. The method of claim 1, wherein the at least one solvent for the production of the liquid composition is chosen from the group consisting of water, at least one monovalent alcohol to trivalent alcohol, at least one polyalcohol and mixtures thereof.

7. The method of claim 1, wherein the pharmaceutical active ingredient is the foaming agent.

8. The method of claim 1, wherein the foaming agent is chosen from the group consisting of anionic surfactants, cationic surfactants, nonionic surfactants, ampholytic surfactants, silicones, fats, fatty acids, fatty acid derivates, phospholipids, sugar derivatives, sphingolipids, glycolipids, and mixtures thereof.

9. The method of claim 1, comprising at least one of:

a complexing agent, a buffer, a thickening agent, an antioxidant and/or a stabilizer.

63. The method of claim 5, wherein the density of the foam is between 0.15 g/ml and 0.8 g/ml as measured by the SITA foam measurement method.

2. A method for the development of a foamable liquid pharmaceutical composition to be applied as a foam to the skin, wherein the foamable liquid composition comprises at least one solvent, at least one pharmaceutical active ingredient, and at least one foaming agent, wherein the method comprises varying the concentration and/or chemical nature of the at least one foaming agent, the at least one solvent and the at least one pharmaceutical active ingredient to form a foam with a foam volume between 450 and 1400 ml, and a foam stability, after a dwell time of up to ten minutes between 55% and 100% of the foam volume that was originally present immediately after the creation of the foam, wherein the foam volume and the foam stability of the foamable composition are determined by a standardized SITA measurement method without the use of a propellant.

62. The method of claim 2, wherein the method comprises varying the concentration, and/or chemical nature of the at least one foaming agent, the at least one solvent and/or the at least one pharmaceutical active ingredient to form a foam with a foam volume between 600 and 1200 ml, and a foam stability after a dwell time of five minutes between 85% and 99% of the foam volume that was originally present immediately after the creation of the foam, wherein the foam volume and the foam stability of the foamable composition are determined by a standardized SITA measurement method without the use of a propellant.

10. A liquid composition suitable for topical use comprising:

a phospholipid foaming agent and at least one solvent; and

a pharmaceutically acceptable active agent;

wherein the liquid composition is capable of mechanically foaming without an additional propellant; and

wherein upon mechanical foaming of 250 ml of the liquid composition results in a foam with a foam volume of at least about 400 ml and a foam stability wherein at least about 50% of the foam volume is still present after about 5 minutes at 25°

C., as determined using a SITA foam measurement.

11. The liquid composition of claim 10, wherein the foam volume is about 450 to about 1400 ml.

12. The liquid composition of claim 10 or 11, wherein the foam volume is about 600 ml to about 1200 ml.

13. The liquid composition of claim 12, wherein at least about 50% of the foam volume is still present after about 10 minutes.

14. The liquid composition of claim 12, wherein about 55% to about 85% of the foam volume is still present after about 5 minutes.

15. The liquid composition of claim 12, wherein about 85% to about 100% of the foam is still present after about 10 minutes.

32. A method for treatment of atopic eczema or neurodermitis comprising the application of a composition of claim 10, containing an immunomodulator, to the skin of a warm-blooded mammal in need thereof.

33. The method of claim 32, wherein the immunomodulator is tacrolimus.

34. The method of claim 32, wherein the composition has a concentration between 0.03 wt. % and 0.1 wt. % of the immunomodulator.

35. A method for treatment of inflammatory or itching skin diseases, psoriasis, dermatitis, neurodermitis or psoriasis, comprising the application of a composition of claim 10, containing comprising a glucocorticoid, to the skin of a warm-blooded mammal in need thereof.

36. The method of claim 35, wherein the glucocorticoid is chosen from the group consisting of-beta-methasone, dexamethasone, predincarbate, mometasone furoate and clobetasonbutyrate.

37. The method of claim 35, wherein the composition contains the glucocorticoid in a concentration between 0.01 wt. % and 0.4 wt. %.

38. A method for treatment of pain, inflammation, rheumatic diseases or acute trauma, comprising the application of a composition of claim 10 containing an analgesic, to the skin of a warm-blooded mammal in need thereof.

39. The method of claim 38, wherein the analgesic is chosen from the group consisting of diclofenac, ketoprofen and ibuprofen in need thereof.

40. The method of claim 38, wherein the composition contains the analgesic in a concentration between 0.1 wt. % and 20 wt. %.

41. A method for treatment of mycotic infections comprising the application of a composition of claim 10, containing an antimycotic agent, to the skin or nails of a warm-blooded mammal in need thereof.

42. The method of claim 41, wherein the antimycotic agent is chosen from the group containing bifonazol and terbinafin.

43. The method of claim 41, wherein the composition contains the antimycotic agent in a concentration between 0.5 wt. % and 10 wt. %.

44. A method for treatment of infections with Gram positive microbes, anaerobic microbes and mycoplasms, or treatment of acne, comprising the application of a composition of claim 10, containing an antibiotic, to the skin of a warm-blooded mammal in need thereof in need thereof.

45. The method of claim 44, wherein the antibiotic is erythromycin.

46. The method of claim 44, wherein the composition contains the erythromycin in a concentration between 2 wt. % and 4 wt. %.

47. A method for treatment of itching of the skin, comprising the application of a composition of claim 10, containing a local anesthetic, to the skin of a warm-blooded mammal in need thereof.

48. The method of claim 47, wherein the local anesthetic is benzocaine and/or lidocaine.

49. The method of claim 47, wherein the composition contains the local anesthetic in a concentration between 1 wt. % and 20 wt. %.

50. A method for treatment of psoriasis, comprising the application of a composition of claim 10, containing calcipotriol, to the skin of a warm-blooded mammal, in need thereof.

51. A method of claim 50, wherein the composition contains the calcipotriol in a concentration between 0.005 wt. % and 0.05 wt. %.

52. A method for treatment of acne acne comedonica or acne papulopustulosa, comprising the application of a composition of claim 10, containing tretinoin, to the skin of a warm-blooded mammal, in need thereof.

53. The method of claim 52, wherein the composition contains the tretinoin in a concentration between 0.05 wt. % and 0.1 wt. %.

54. A method for treatment of hair loss, comprising the application of a composition of claim 10, containing minoxidil, to the skin of a warm-blooded mammal, in need thereof.

55. The method of claim 54, wherein the composition contains the minoxidil in a concentration between 3 wt. % and 6 wt. %.

56. A method for treatment of superficial wounds, comprising the application of a composition of claim 10, containing dexpanthenol, to the wound of a warm-blooded mammal, in need thereof.

57. The method of claim 56, wherein the composition contains the dexpanthenol in a concentration between 0.03 wt. % and 1 wt. %.

58. A method for treatment of herpes and the side effects accompanying herpes, comprising the application of a composition of claim 10, containing acyclovir, to the skin of a warm-blooded mammal, in need thereof.

59. The method of claim 58, wherein the composition contains the acyclovir in a concentration between 3 wt. % and 7 wt. %.

60. A method for treatment of mild to medium severe psoriasis of the scalp, comprising the application of a composition of claim 10, containing salicylic acid, to the skin of a warm-blooded mammal, in need thereof.

61. The method of claim 60, wherein the composition contains the salicylic acid in a concentration between 8 wt. % and 12 wt. %.

16. A liquid composition suitable for topical use comprising with at least one systemically and/or topically acting pharmaceutical active ingredient, wherein the composition in addition to a pharmaceutical active ingredient also comprises at least one solvent and least one phospholipid foaming agent,

wherein the composition has such a fluid consistency that it forms a foam when applied without the use of an additional propellant,

wherein the chemical nature and/or concentration of the at least one phospholipid foaming agent, the at least one solvent and/or the at least one pharmaceutical active ingredient are attuned to each other so that the composition can be mechanically foamed without the use of an additional propellant,

wherein the foam so created has a foam volume of between 450 and 1400 ml,

wherein the foam stability has, after a dwell time of up to ten minutes between 55% and 100% of the foam volume that was originally present immediately after the creation of the foam, wherein both the foam volume and the foam stability can be determined by a standardized SITA foam measurement method.

17. The liquid composition of claim 16, wherein the foam has a density of about 0.05 g/ml and about 0.8 g/ml.

18. The liquid composition of claim 17, wherein the foam has a density of about 0.15 g/ml and about 0.4 g/ml.

19. The liquid composition of claim 16, wherein the solvent is a polyvalent alcohol.

20. The liquid composition of any one of claim 16, wherein the solvent, is selected from the group consisting of water, least one polyvalent to trivalent alcohol, at least one polyalcohol and mixtures thereof, and the phospholipid foaming agent, is a phospholipid isolated from plant components and/or a phospholipid mixture.

21. The liquid composition of claim 16, wherein the at least one active ingredient is an active ingredient for use on humans or animals and is chosen from the group comprising local anesthetics, anti-allergic agents, dermatics, active ingredients against flu infections and colds, active ingredients for the treatment of neuropathies, active ingredients for the treatment of disturbed circulation, chemotherapy drugs, quinine, antimycotics, antibiotics, thalidomide, serotonin, eicosanoids, analgesics, anticonvulsants, nonsteroidal antirrheumatics, leukotrienes, leukotriene inhibitors, androgens, antiandrogens, corticoids, opiate receptor antagonists, blood clotting inhibitory substances, thrombocyte aggregation inhibitors, histamine antagonists, regulatory and enzymatically acting peptides and proteins, nucleic acids (single and double-stranded DNA, single and double-stranded RNA, snRNA, DNA oligonucleotides, RNA oligonucleotides) and oligopeptides, antipruritics, antidiabetics, prostaglandins, prostaglandin synthesis inhibitors, antiviral-acting or virostatic-acting substances, antimicrobial-acting substances, active ingredients against prions, immune suppressants, hormones, active ingredients for treatment of warts or wounds, especially chronic wounds, vitamins, plant extracts or essences of plant extracts, psychoactive drugs, active ingredients influencing sleep, analeptics, general anesthetics, muscle relaxants, antiepileptics, antiparkinson agents, antiemetics, antiparasitics, ganglion-active substances, sympathetic-active substances, parasympathetic-active substances, antibacterial-acting drugs, calcium antagonists, cardiovascular agents, antiasthmatics, antitussives, expectorants, hepatics, diuretics, choleretics, disinfectants, trace elements, antiinfectives, cytostatics, antimetabolites, hormone antagonists, immune modulators, and salts thereof.

22. The liquid composition of claim 21, wherein the composition comprises between 0.1 wt. % and 20 wt. %, of at least one analgesic.

23. The liquid composition of claim 21, wherein the composition comprises between 0.01 wt. % and 10 wt. %, of at least one antimycotic.

24. The liquid composition of claim 21, characterized in that the composition comprises at least one corticoid active ingredient in a concentration between between 0.1 wt. % and 5 wt. %.

25. The liquid composition of claim 21, characterized in that the composition comprises at least one topical anesthetic in a concentration between 3 wt. % and 15 wt. %,

26. The liquid composition of claim 21, characterized in that the composition comprises the at least one immunomodulator in a concentration between 0.03 wt. % and 0.1 wt. %.

27. The liquid composition of claim 21, wherein the phospholipid foaming agent is a phosphatidyl choline isolated from soy beans, wherein the concentration of the phosphatidyl choline in the phospholipid foaming agent is between 50 wt. % and 95 wt. %, in relation to the dry substance of said phospholipid foaming agent.

28. The liquid composition of claim 27, wherein at most 15 wt. % of lyso-phosphatidyl choline, at most 10 wt. % of phosphatidic acid and at most 10 wt. % of phosphatidyl ethanolamine are contained in the phospholipid foaming agent.

29. The liquid composition of claim 27, wherein the phosphatidyl choline contained in the phospholipid foaming agent has an acid number of at most 10, a peroxide number of at most 10, and an oil concentration of at most 6 wt. %.

30. The liquid composition of claim 21, characterized in that the composition has the phospholipid foaming agent in a concentration 4 wt. % and 15 wt. %.

31. The liquid composition of claim 21 wherein the alcohol is propylene glycol, and is present in the composition in a concentration between 2 wt. % and 25 wt. %.

64. The liquid composition of claim 16, wherein the foam so created has a foam volume of between 600 ml and 1200 ml.

65. The liquid composition of claim 16, wherein the foam has such a stability that the foam has after a dwell time of up to ten minutes between 85% and 99% of the foam volume that was originally present immediately after the creation of the foam.