ANTISEPTIC, ANTISEBORRHEIC, EXFOLIATING COMPOSITION TO REMOVE OR PREVENT ACNE

Abstract

The invention refers to an antimicrobial, exfoliating and seboregulating hydrosoluble composition comprising a combination of diallyl disulphide modified oxide (DDMO) and alpha hydroxyethanoic acid (glycolic acid), which acts removing bacteria affecting the skin including those caused by acne, said composition also provides deep cleansing, exfoliating action, reduces epidermal cohesion facilitating cellular change, preventing the occurrence of several forms of acne in the skin and additionally producing seboregulating effects by avoiding blockage of sebaceous glands.

Claims

1. An antimicrobial, exfoliating and seboregulating pharmaceutical hydrosoluble composition to remove or prevent skin microbial injuries, including acne, characterized in that it comprises from 0.001 to 10% p/w of the DDMO composition, from 1 to 12% p/w of alpha hydroxyethanoic acid (glycolic acid), from 0.3 to 24% p/w of one or more surfactants, from 0.3 to 10% p/w of a moisturizing agent, from 0.2 to 10% p/w of an aromatizing agent and from 40 to 70% p/w of the composition of an aqueous solvent.

2. The composition according to claim 1, characterized in that the surfactants are selected from the group consisting of lineal alkylbenzensulfates and ionic alkyl sulfates.

3. The composition according to claims 1 and 2, characterized in that the surfactants preferably are sodium lauryl sulfate, sodium lauryl ether sulfate and ammonium lauryl sulfate.

4. The composition according to claim 1, characterized in that the moisturizing agent is selected from the group consisting of ethylene glycol, propylene glycol, glycerin, sorbitol, low molecular weight polyethylenes, polyoxyethylated glycerols, polyoxyethylated sugars.

5. The composition according to claim 1, characterized in that the aromatizing agent is selected from those available for the pharmaceutical and food industry.

6. The composition according to claim 1, characterized in that the solvent is selected from water and water-hydrosoluble alcohol mixtures.

7. The use of the composition according to claim 1, for making a medicine to remove, reduce or prevent acne.

8. The use of the composition according to claims 1 to 6, for making a medicine to remove bacteria causing acne, providing deep and delicate cleansing to normal and oily skin, providing exfoliating action, eliminating death cells from the skin, removing grease and fat excess present in skin with acne, avoiding the obstruction of pores, removing the comedonal block and avoiding the formation of new blackheads and pustules.

9. A method for removing, reducing and preventing acne, characterized in that it comprises to administer the skin of an individual in need of said treatment an antimicrobial and antiseptic pharmaceutical hydrosoluble composition according to any of claims 1 to 6.

Description

DESCRIPTION OF THE INVENTION

[0039] The present invention is related to antimicrobial, exfoliating and seboregulating pharmaceutical hydrosoluble compositions comprising from 0.001 to 10% p/w of the DDMO composition, from 1 to 12% p/w of alpha-hydroxyethanoic acid (glycolic acid), from 0.3 to 24% p/w of one or more surfactants, from 0.3 to 10% p/w of a moisturizing agent, from 0.2 to 10% p/w of an aromatizing agent and from 40 to 70% p/w of the composition of an aqueous solvent.

[0040] Particularly, the object compositions of the present invention comprise one or more surfactants selected from the group consisting of lineal alkyl benzene sulfates and ionic alkyl sulfates.

[0041] The surfactants useful in the object compositions of the present invention preferably are sodium lauryl sulfate and sodium lauryl ether sulfate.

[0042] The ionic alkyl surfactants, such as sodium lauryl sulfate that is an anionic surfactant, are used in a variety of pharmaceutical non-parenteral formulations. For example, the sodium lauryl sulfate is a detergent and moisturizing agent, effective in acid, alkaline solutions and in hard water. It is used in medicated shampoos, such as skin cleaner and dentifrices, it is usually known as “Cosmetic Detergent”, makes foam and bubbles and is good for removing grease and oil from skin and hair.

[0043] Likewise, the sodium lauryl ether sulfate is the most frequently used active anion surfactant in the manufacture of cleaning, scrubbing and domestic washing products, as well as cosmetic and personal hygiene products. The sodium lauryl ether sulfate does not irritate the skin and if from natural origin; additionally it is valued for its easy degradations and properties in relation to the formation of foam. The sodium lauryl ether sulfate is mainly used in the production process of shampoos, liquid soaps, face skin creams, dental creams, etc.

[0044] The surfactant preferably used in the present invention are sodium lauryl sulfate, sodium lauryl ether sulfate and ammonium lauryl sulfate.

[0045] The moisturizing agent is selected from the group consisting of ethylene glycol, propylene glycol, glycerin, sorbitol, low molecular weight polyethylenes, polyoxyethylated glycerols, polyoxyethylated sugars, for example, MEA acetamide, and the like. Preferably, the moisturizing agent is glycerin, which has a wide variety of applications, such as emulsifier, softening agent, laminate, stabilizing and moisturizing agent for baking shop, ice-cream shop and cigar store, in body lotions, mouthwashes, as protecting means for freezing of red blood cells, sperm, corneas and other tissues in printing inks, paint resins; antifreezing mixtures; and as raw material for nitroglycerin. It is used in the manufacture of countless prepared pharmaceuticals and cosmetics; for example in soaps, glycerin increases its detergency, whitening and softening of the skin. Between 8-15% of glycerin can be found in the compositions of these soaps.

[0046] Other moisturizing agents useful in the compositions claimed in the present invention comprise among others:

[0047] A aromatizing agent selected from any of the available ones for the pharmaceutical and food industry.

[0048] An aqueous solvent, which is selected from water and water-hydrosoluble alcohol mixtures.

[0049] With these elements, it is possible to extract a wide range of antimicrobial, exfoliating and seboregulating pharmaceutical compositions containing DDMO and alpha-hydroxyethanoic acid (glycolic acid), useful in treating and preventing skin microbial injuries.

[0050] Said compositions contribute to eliminate bacteria causing acne providing a deep and delicate cleansing of the skin; even in oily skins, improving the habitual look and freshness. In addition to its antimicrobial action, it provides an exfoliating action, reducing the epidermal adhesion and facilitating the cellular change, eliminating dead skin cells. Also, they remove the grease and oil excess present in the acne skin, thus preventing obstruction of the pores, removing comedonal block and avoiding formation of new blackheads and pustules.

[0051] The information obtained from microbiologic tests (antimicrobial challenge) of the DDMO and alpha-hydroxyethanoic acid (glycolic acid) against several bacteria, has proven the great antibacterial capacity of the formulations, insisting on the results against Propionibacterium acnes, thus proving the removal of said bacteria in a matter of seconds.

[0052] The antimicrobial action mechanism of DDMO, probably comprises the following:

[0053] 1. Alteration of the microbial mechanism, inhibiting the action of 11 essential enzymes for cellular respiration of the microorganism. This inhibiting effect is created from the chemical reaction of the sulfhydryl radicals of DDMO about the molecular structure of the sulfurated enzymes of the microorganism, whether by inserting sulfurated radicals or by modifying the enzyme protein, thus causing death of the microorganism.

[0054] 2. Through reactions of oxide-reduction creating free radicals (ROS), which by oxidative stress break the cellular wall of the microorganism, by acting “sequestering” oxygen serving as link between the NAG (n-Acetyl glucosamine acid) and NAM (N-Acetyl muramic acid) chains, thus weakening the microorganism wall causing rupture and thereby death of the microorganism.

[0055] 3. Inhibition of the genetic transcription process and unfolding of the microorganism proteins, through the activation of the polymerase ARN enzyme, which is an enzyme, since being of sulfurated composition, is vulnerable to chemical attack from the DDMO.

[0056] 4. Alteration of the metal metabolism in the microorganism, also causing metabolic alterations therein.

[0057] The foregoing has been inferred from studies made with allicin, reported by Yosuda et al, Biosci. Biotechnol. Biochem., 63(3) 591-594, 1999; Feldherg et al, Antimicrobial Agents and Chemotherapy, Dec. 1988, 1763-1768; Munchberg et al, Org. Biomol. Chem., 2007, 5, 1505-1518; among others. Considering that DDMO is an stabilized allicin molecule owing its antimicrobial action precisely to this allicin fragment, whose activity is preserved without alteration as shown in the microbiological tests.

[0058] The microbiological challenges were made with collection microorganisms, universally required to test the product effectiveness. The results proved that in 30 seconds of contact with the composition from Example 1, 100.00% was removed from the challenged microorganisms, including Candida albicans. The results from the study are shown in Table 1.

TABLE-US-00001 TABLE 1 Studies from microbial challenge Test Microorganism Contact Time 30 Sec Escherichia coli 100% ATCC 10536 Pseudomona aerugiosa 100% ATCC 9027 Klebsiellapneumoniae 100% ATCC 10031 Proteus vulgaris 100% ATCC 6380 Staphylococcus aureus 100% ATCC 6538 Staphylococcus epidermis 100% ATCC 12228 Candida albicans 100% ATCC 1031

[0059] Additionally, challenge tests were made against Propionilbacterium acnes, anaerobic bacteria previously referred to as one of the main causes of infection caused by acne, thus obtaining excellent results, such as it is shown below in Table 2.

TABLE-US-00002 TABLE 2 Contact Time Eradication Test Microorganism 30 seconds 60 seconds Propionibacterium acnes 98% 99.999%

[0060] The results of these microbial challenges are more encouraging that those reported by Fujisawa et al, Biosci. Biotechnol. Biochem. 73 (9) 1984-1955, 2009; Tsao et al Journal of Medical Microbiology (2007) 56, 803-808. And they confirm the review by Ankri and Mirelman, Microbes and Infection, 2, 1999, 125-129 and by Domingo and López-Brea in Rev. Esp. Quimioterap. Dec. 2003, Vol. 16 (no. 4) 285-293 (2003).

Example 1

[0061] An antimicrobial and antiseptic hydrosoluble composition was prepared containing:

TABLE-US-00003 Component Kg a-hydroxyethanoic acid 57.1 DDMO 4 Sodium lauryl sulfate 50 Sodium lauryl ether sulfate 50 Glycerin 2.5 Blue fragrance 3 Purified water 333.4

Example 2

[0062] A second composition was prepared containing the following elements:

TABLE-US-00004 Component Kg a-hydroxyethanoic acid 58 DDMO 5 Sodium lauryl sulfate 40 Sodium lauryl ether sulfate 60 Ethylene glycol 2.5 Floral fragrance 3 Purified water 331.5

Example 3

[0063] A third example of the object compositions of the present invention is shown, thus proving that the embodiments of the same only limit to preserving the homogeneous distribution aspects of all components.

TABLE-US-00005 Component Kg a-hydroxyethanoic acid 57.1 DDMO 4 Sodium lauryl ether sulfate 100 Sorbitol 2 Blue fragrance 3 Purified water-ethanol (9:1) 333.9

[0064] Clinical Trials:

[0065] A clinical trial was made applying the product of the present invention (example 1) during 28 days to 20 patients with moderate acne, according to the classification shown in Table 3 below.

TABLE-US-00006 TABLE 3 Grade* Description 0 Clean skin with no inflammatory or non-inflammatory wounds 1 Almost clean; Little non-inflammatory wounds and no more tan two inflammatory wounds 2 Middle severity; greater than grade 1; some non-inflammatory wounds, few inflammatory wounds (only papules/pustules; no nodular wounds) 3 Moderate severity; greater than grade 2; many non-inflammatory wounds and several can be inflammatory, but no more than two nodular wounds. 4 Severe; greater than grade 3; many inflammatory and non-inflammatory wounds; and some nodular wounds.  FDA’s classification scale of acne
The number of wounds from each patient was counted by two different observers before treatment and during the same each week. The resulting data is shown in table 4, wherein it can be seen that the treatment gave an average reduction close to 35% of the active wounds after 28 days of treatment.

TABLE-US-00007 TABLE 4 No. Of Inflammatory Wounds Number Day 0 7 days 14 days 21 days 28 days 1 58 +/− 5 51 +/− 5 45 +/− 4 41 +/− 3 37 +/− 3

[0066] On the other hand, patients were asked to assess the presence of grease, through the use of drying paper, measuring the number of sheets needed in order not to get the forehead stained 2 hours after cleaning with the product, thus discovering that patients considerably reduced the number of drying sheets used for cleaning the grease, the results are shown in Table 5.

TABLE-US-00008 TABLE 5 No. Of Sheets Day 0 7 days 14 days 21 days 28 days 5 +/− 2 2 +/− 2 1 +/− 2 1 +/− 1 1 +/− 1

[0067] The results show that the antiseptic, antiseborrheic and exfoliating composition of the present invention is able to achieve an effective treatment for seborrhea and acne. These results show that the treatment for these disorders according to the present invention is clearly better than the pre-existing methods.