Multifunctional topical formulation for the treatment of acne vulgaris and other skin conditions

Abstract

A two-part aqueous composition for treating skin ailments, such as acne vulgaris, includes an acidic part having salicylic acid and an -hydroxy acid, and an alkaline part having an alkaline nitrite salt. The -hydroxy acid is preferably glycolic acid, lactic acid, malic acid, mandelic acid or a combination thereof. The alkaline nitrite salt is preferably sodium nitrite. The acidic part and the alkaline part are an acidic aqueous solution and an alkaline aqueous solution, respectively, which may either be mixed with one another then applied to an affected portion of a patient's skin or, alternatively, may be sequentially applied to the affected portion of the patient's skin, preferably within 15 minutes of one another.

Claims

1. A method for treating a skin ailment caused by a microbial proliferation, comprising the steps of: formulating an acidic aqueous solution having salicylic acid and an -hydroxy acid, with said acidic aqueous solution having no lactic acid and no glycolic acid; formulating an alkaline aqueous solution having an alkaline nitrite salt; and sequentially applying said acidic aqueous solution directly to the portion of the skin of the patient and three minutes to fifteen minutes later applying said alkaline aqueous solution directly to the portion of the skin of the patient to which said acidic aqueous solution has already been applied thereby producing nitrous acid, the activity of which supplements that of said acidic aqueous solution for treating the skin ailment caused by the microbial proliferation afflicting the portion of the skin of the patient; wherein the -hydroxy acid concentration is in the range of from about 0.5% to about 5.0% as calculated upon a combined volume of said acidic aqueous solution and said alkaline aqueous solution.

2. The method for treating a skin ailment caused by a microbial proliferation according to claim 1, wherein said acidic aqueous solution includes an -hydroxy acid selected from the group consisting of malic acid, mandelic acid and a combination thereof.

3. The method for treating a skin ailment caused by a microbial proliferation according to claim 1, wherein said alkaline aqueous solution includes sodium nitrite as said alkaline nitrite salt of said alkaline part.

4. The method for treating a skin ailment caused by a microbial proliferation according to claim 1, wherein the microbial proliferation is caused by a bacterial skin infection.

5. The method for treating a skin ailment caused by a microbial proliferation according to claim 1, wherein the microbial proliferation is caused by a viral skin infection.

6. The method for treating a skin ailment caused by a microbial proliferation according to claim 1, wherein the microbial proliferation is caused by a fungal skin infection.

7. A method for treating a skin ailment caused by a microbial proliferation, comprising the steps of: formulating an acidic aqueous solution having salicylic acid and mandelic acid, said mandelic acid being an -hydroxy acid and with said acidic aqueous solution having no lactic acid and no glycolic acid; formulating an alkaline aqueous solution having an alkaline nitrite salt; and sequentially applying said acidic aqueous solution directly to the portion of the skin of the patient and three minutes to fifteen minutes later applying said alkaline aqueous solution directly to the portion of the skin of the patient to which said acidic aqueous solution has already been applied thereby producing nitrous acid, the activity of which supplements that of said acidic aqueous solution for treating the skin ailment caused by the microbial proliferation afflicting the portion of the skin of the patient; wherein the mandelic acid concentration is in the range of from about 0.2% to about 5.0% as calculated upon a combined volume of said acidic aqueous solution and said alkaline aqueous solution.

8. The method for treating a skin ailment caused by a microbial proliferation according to claim 7, wherein said acidic aqueous solution further includes an additional -hydroxy acid.

9. The method for treating a skin ailment caused by a microbial proliferation according to claim 7, wherein said additional -hydroxy acid is malic acid.

10. The method for treating a skin ailment caused by a microbial proliferation according to claim 7, wherein said alkaline aqueous solution includes said alkaline nitrite salt of said alkaline part is sodium nitrite.

11. The method for treating a skin ailment caused by a microbial proliferation according to claim 7, wherein the microbial proliferation is caused by a bacterial skin infection.

12. The method for treating a skin ailment caused by a microbial proliferation according to claim 7, wherein the microbial proliferation is caused by a viral skin infection.

13. The method for treating a skin ailment caused by a microbial proliferation according to claim 7, wherein the microbial proliferation is caused by a fungal skin infection.

14. A method for treating a skin aliment caused by a microbial proliferation, comprising the steps of: formulating an acidic aqueous solution having salicylic acid and an -hydroxy acid, with said acidic aqueous solution having no lactic acid and no glycolic acid; formulating an alkaline aqueous solution having an alkaline nitrite salt; and sequentially applying said alkaline aqueous solution directly to the portion of the skin of the patient and three minutes to fifteen minutes later applying said acidic aqueous solution directly to the portion of the skin of the patient to which said alkaline aqueous solution has already been applied thereby producing nitrous acid, the activity of which supplements that of said acidic aqueous solution for treating the skin aliment caused by the microbial proliferation afflicting the portion of the skin of the patient; wherein the -hydroxy acid concentration is in the range of from about 0.5% to about 5.0% as calculated based on a 1:1 combined volume of said acidic aqueous solution and said alkaline solution.

15. The method for treating a skin aliment caused by a microbial proliferation according to claim 14, wherein said acidic aqueous solution includes an -hydroxy acid selected from the group consisting of malic acid, mandelic acid and a combination thereof.

16. The method for treating a skin aliment caused by a microbial proliferation according to claim 14, wherein said alkaline aqueous solution includes said alkaline nitrite salt of said alkaline part is sodium nitrite.

17. The method for treating a skin ailment caused by a microbial proliferation according to claim 14, wherein the microbial proliferation is caused by a bacterial skin infection.

18. The method for treating a skin ailment caused by a microbial proliferation according to claim 14, wherein the microbial proliferation is caused by a viral skin infection.

19. The method for treating a skin ailment caused by a microbial proliferation according to claim 14, wherein the microbial proliferation is caused by a fungal skin infection.

Description

DETAILED DESCRIPTION OF ADDITIONAL PREFERRED EMBODIMENTS

(1) In the application of this technology, it is often preferable to incorporate a thickening (gelling) agent to one or both parts of the two-part system, to add body to the composition. This allows for a greater deposition of the mixed material to skin surfaces, and a greater duration of action. Gelling agents for use in the present invention include polysaccharides extracted from legume seeds, such as the galactomannans, including guar gum and locust bean (carob) gum. Other gelling agents include high molecular weight polyoxyalkylene crosslinked acrylic polymers as well as the highly preferred cellulosics such as hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, methylpropyl cellulose, among others, including high molecular weight polyethylene glycols, polyacrylamide and polyacrylamide sulfonates, and crosslinked polyvinylpyrrolidones, among others.

(2) As indicated in the title of this inventive composition, Multifunctional Topical Formulation for the Treatment of Acne Vulgaris and Other Skin Conditions, there are a variety of other microbially-associated skin disorders which can benefit substantially from the application of compositions incorporating the inventive powerful topical antibacterial technology. These conditions, as referenced in Section 2. Description of the Related Art, include a host of other skin afflictions where microbial proliferation is a major problem. Examples in the category of bacterial skin infections and related conditions are boils, folliculitis, carbuncles, furuncles, cellulitis, abscesses, impetigo, and erysipelas. There is indeed a great need for an antimicrobial composition to treat diabetic foot ulcers, which result from deficient blood flow to peripheral tissues, such as in the feet of diabetes sufferers, where the necrotic tissue becomes a source of nutrients to invading bacteria. These often lead to foot amputation. There is the intriguing possibility, in such cases, that the nitrous oxide, NO, which is generated from nitrous acid degradation, as shown earlier in this Specification (3HNO.sub.2.fwdarw.H.sup.++2NO+NO.sub.3.sup.+H.sub.2O) can penetrate to the underlying capillaries and stimulate their dilation, leading to enhanced blood flow, thereby helping to counter the ischemia resulting from diminished oxygen supply to the affected tissues. Also of potential benefit from the inventive technology are those afflictions related to common fungal infections, including athlete's foot, jock itch, ringworm, and yeast infections.

(3) The present invention is illustrated by the following Examples. All parts and percentages therein, as well as the Specification and claims, are by weight, unless otherwise specified. The following examples, which are non-limiting, further describe preferred embodiments within the scope of the present invention. Many variations of these Examples are possible without departing from the spirit of the invention.

Example 1

(4) Example 1 demonstrates the antimicrobial activity of a formulation in which Parts A and B were mixed together immediately prior to their evaluation against the gram-positive aerotolerant, anaerobic bacterium Propionibacterium acnes (P. acnes) that is associated with acne. The formulas for Parts A and B of this inventive composition were as follows:

(5) Part A:

(6) TABLE-US-00004 COMPONENT Percentage Isopropyl alcohol (70%) 35.70 Sodium benzoate 0.04 Salicylic acid 1.00 Mandelic acid 1.00 PLURONIC P103 0.10 (BASF Corporation) A difunctional block copolymer surfactant terminating in primary hydroxyl groups. A nonionic surfactant that is 100% active and relatively nontoxic. Propylene glycol 10.00 NATROSOL 250MR 2.10 (Ashland Specialty Chemical) (hydroxyethylcellulose) Titanium dioxide (fine) 0.10 Deionized water 49.96 pH adjusted to 2.8 with conc. NaOH

(7) Part B:

(8) TABLE-US-00005 COMPONENT Percentage PLURONIC P103 0.1 (BASF Corporation) A difunctional block copolymer surfactant terminating in primary hydroxyl groups. A nonionic surfactant that is 100% active and relatively nontoxic. Dodecylbenzene sulfonate, Na.sup.+ 0.1 Sodium Nitrite (pure basis) 1.0 NaOH (10N) ~2.2 Carbopol 980 (polymer is a 1.0 crosslinked polyacrylate polymer) Titanium dioxide (fine) 0.1 Deionized Water ~95.5

(9) pH adjusted to 8.5The pH of the mixed composition was 3.25

(10) The microbiological results from testing this freshly mixed composition on the P. acnes bacterium, were as follows:

(11) Test Organism: P. acnes ATCC 6919

(12) Initial Suspension: 2.310.sup.7

(13) TABLE-US-00006 Challenge Inoculum Recovered Log Test Sample (Log#cfu/ml) (Log#cfu/ml) Reduction Inventive 2.3 10.sup.6 0 >>5.36 Composition (6.36) (0) rdk110PGX235 A + B Acne Free 2.3 10.sup.6 >1 10.sup.4* <<2.5 Terminator 10 (6.36) (>>4.0).sup. PROACTIV 2.3 10.sup.6 >1 10.sup.4* <<2.5 SOLUTION (Rodan and (6.36) (>>4.0).sup. Fields) Control (Saline) 2.3 10.sup.6 2.3 10.sup.6 (6.36) *Approximate Minimum Count
It can be noted, from the Log Reduction data, that the efficacy of a specific formulation of the inventive composition is at least 1,000 times (>3 logs) greater than any of these commercial products, and particularly that approximately 6 logs (1 million) of organisms, per ml of test medium, were destroyed within one minute of contact with this representative formulation of the inventive composition. The other two commercial formulations, each of which contain 2% of salicylic acid as cf. the 0.5% salicylic acid in the mixed composition, showed no significant reduction of the P. acnes organism count, after the 60-second contact. This is not unexpected because the primary focus of these two commercial products was on the acne pustules, papules, etc., rather than the microorganism that is invariably present on the skin of acne patients, as a probable exacerbant of their skin affliction.

Example 2

(14) Example 2 illustrates the efficacy of the formulation shown in Example 1 in the treatment of acne-afflicted subjects. It was a prospective, comparative, randomized clinical study involving twenty-three female and twenty-one male individuals, aged 9-29; twenty-two of whom had lesions on their faces, chests and backs; twelve on their faces only; and ten on their faces and backs. The patients were randomly divided in two groups, as follows:

(15) Control: Conventional treatment with systemic antibiotics and topical retinoids;

(16) Experimental: Topical treatment of the lesions with the premixed test formulation, twice a day for up to 4 weeks, with photos taken every week.

(17) The following summary of findings was provided by the clinician who coordinated the study: The new treatment had the same efficacy as the conventional treatment The advantage is that the new treatment is potentially safer Conventional treatment is based on systemic antibiotics given for long periods and retinoids. Long term antibiotics can disrupt endogenous normal flora, and retinoids have been associated with hypertriglyceridemia and a high risk of suicide in adolescents

Example 3

(18) Example 3 illustrates the efficacy of the formulation shown in the treatment of acne-afflicted subjects, when the Part A component is first only applied to the individual acne blemishes, and then the Part B application follows shortly thereafter, uniformly spread over the whole skin area where the acne is evident. The application of the Part A component is done by fingertip to the individual spots, while the Part B application is accomplished with a cotton swab. The Part A formulation has a higher viscosity, by virtue of inclusion of a NATROSOL (hydroxyethylcellulose) thickener in its composition. Part B, which is activated to form nitrous acid primarily at the site of the acne infections, has a lotion-promoting component, for example, SEPIGEL (a thickener, stabilizer or emulsion for use in the manufacture of cosmetic, dermocosmetic or pharmaceutical preparations) which is often found in such types of formulations. The Part B also contains Allantoin (a chemical compound with formula C.sub.4H.sub.6N.sub.4O.sub.3; also known as 5-ureidohydantoin or glyoxyldiureide), which is recognized by cosmeceutical chemists to stimulate healthy, normal tissue formation. It has been classified by the FDA as an over-the-counter, Category I (safe and effective) active ingredient skin protectant.

(19) Part A:

(20) TABLE-US-00007 COMPONENT Percentage Isopropyl alcohol (70%) 35.70 Sodium benzoate 0.04 Salicylic acid 1.00 Mandelic acid 1.00 PLURONIC P103 0.10 (BASF Corporation) A difunctional block copolymer surfactant terminating in primary hydroxyl groups. A nonionic surfactant that is 100% active and relatively nontoxic. Propylene glycol 10.00 Natrosol 250HHR 1.30 (hydroxyethylcellulose) Blue #1 0.1% solution 0.05 Deionized water 50.290 Sodium Hydroxide 20% soln 0.52

(21) pH of part A formulation was 3.42

(22) Part B:

(23) TABLE-US-00008 COMPONENT Percentage PLURONIC P103 0.10 (BASF Corporation) A difunctional block copolymer surfactant terminating in primary hydroxyl groups. A nonionic surfactant that is 100% active and relatively nontoxic. Dodecylbenzene sulfonate, Na.sup.+ 0.10 Sodium Nitrite (pure basis) 1.00 NaOH (20% solution) 0.05 SEPIGEL 305 0.25 Allantoin 0.10 Xanthan Gum 0.10 Deionized Water 98.30 pH adjusted to 8.5

(24) A number of young men and women, who had acne outbreaks on their skin, had applied this inventive composition ad seriatim, where the Part A was allowed to remain for a few minutes prior to smoothing on the Part B, as described above. They all reported that the individual acne blemishes had cleared within several days of application of this composition on a 2/day basis.

Example 4

(25) Example 4 illustrates the efficacy of the formulation shown in Example 1 in the treatment of non-acne skin conditions. Within several days of twice per day application of the mixed formulation, one individual with intractable folliculitis reported a remarkable reduction of the inflamed area, which theretofore was resistant to a variety of other medications. A young woman with widespread acne covering her upper torso and face, to a degree that she avoided appearing in public areas, had applied the composition twice a week to the affected areas. After one month the condition had completely disappeared. She also had suffered from pityriasis alba, which also was no longer evident one month after the twice-per-week application.

(26) While only several embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that many modifications may be made to the present invention without departing from the spirit and scope thereof.