EA041341B1 - ANTIMICROBIAL COMPOSITIONS FOR APPLICATION TO HUMAN SKIN - Google Patents

Description

The field of technology to which the invention belongs

The invention relates to topical antimicrobial compositions, i. e. for application to human skin. The antimicrobial compositions of the present invention contain a vitamin B3 compound and provide long-term protection against pathogens and other undesirable microorganisms.

Prerequisites for the creation of the invention

Antiseptics are antimicrobial agents that are applied to living tissues, such as the skin, to reduce the chance of infection. Antiseptics are generally distinguished from antibiotics by their ability to be transported through the lymphatic system to kill bacteria in the body, and from disinfectants, which kill microorganisms found on inanimate objects.

Typically, the skin contains several different microorganisms at concentrations in excess of millions or even billions of colony forming units (CFU) per square centimeter (cm ² ). Many of these organisms are harmless, but various pathogenic species such as E. coli or S. aureus are also present. In addition, other unwanted bacteria are found on the skin, such as S. epidermidis, which are generally not pathogenic but are believed to cause body odor.

Skin hygiene is a high priority for today's consumers. Liquid antimicrobial compositions are commonly used by consumers for direct protection against microorganisms. An example is the use of hand sanitizers designed to disinfect hands without the use of water.

A common ingredient in liquid antimicrobial compositions are alcohols, usually ethanol or isopropanol. However, alcohols have short-term activity due to their rapid evaporation. Alcohols are most effective when combined with distilled water. A mixture containing 60% total alcohols is effective against a wide range of bacteria.

US 2015/258003 A1 (Gojo Industries Inc) describes an effective handwash composition for medical personnel that maintains or improves skin hydration, wherein the composition contains at least one O ₁ -C6 alcohol, at least one phytochemical compound with anti-inflammatory properties, at least one enzyme or coenzyme that promotes the formation of the stratum corneum of the epidermis, and deposition enhancer. Vitamin B3 (niacin) is mentioned as an example of a stratum corneum enhancer.

CN 1043 82766 A (Ou Lingong, 2015) discloses an example of an anti-pigmentation composition that contains 0.8%, 1.5% polyvinylpyrrolidone, 0.7% Hydrocotyle Asiatica extract, 0.5% astragaloside A, 8% aloe extract, 9% cob seed extract, 4.5% purslane extract, 3.5% vitamin B3, 35% ethanol, 9% propylene glycol and 27.5% water.

Vitamin B3 or its amide (niacinamide) are both mentioned in the prior art as a suitable ingredient for skin care products, since vitamin B3 and niacinamide are known to have some properties that are beneficial for the skin, such as preventing cellulite, increasing the formation of stratum corneum, treatment of skin irritation and improvement of skin water absorption. Niacinamide is also used as an active skin lightening agent. In addition, niacinamide is used to treat many inflammatory skin conditions such as acne vulgaris, psoriasis, and atopic dermatitis.

WO 2002/22102 A1 (Johan Asplund) describes a cosmetic composition suitable for topical application to the skin or hair, comprising:

(a) from about 0.0001 to about 10% by weight of a biologically active enzyme;

(b) about 0.1% to about 20% by weight of a polyhydric alcohol; and (c) about 0.1% to about 20% by weight of a skin care active selected from vitamin B3, panthenol, vitamin E, acetate. vitamin E, retinol, retinyl propionate, retinyl palmitate, retinoic acid, vitamin C, theobromine, α-hydroxy acid, farnesol, phytantriol, salicylic acid, and mixtures thereof.

WO 2015/172801 Al (Unilever) describes the use of niacinamide to induce the secretion of antimicrobial peptides (AMP) by keratinocytes when applied to the external surface of the human body. In the examples of this document, niacinamide is added to Vaseline™ and applied to the skin.

One of the problems associated with the use of vitamin B3 or niacinamide in aqueous compositions is the formation of deposits.

Brief description of the invention

The present inventors surprisingly found that a composition containing a combination of 55-70% by weight of ethanol and isopropanol and 0.75-1% by weight of a vitamin B3 compound such as niacinamide provides synergistic microbial protection when applied to human skin.

Compared to using ethanol and isopropanol alone, or alone

- 1 041341 vitamin B3, which is used as niacinamide, the combined use of these antimicrobial components in accordance with the present invention provides long-term protection against bacteria.

The authors also found that the presence of 3-10 wt.% propylene glycol in the antimicrobial composition prevents the formation of deposits, especially if the vitamin B3 compound, which is used as niacinamide, and propylene glycol are present in a weight ratio of at least 1:20.

Thus, the present invention relates to an antimicrobial composition for application to human skin, said composition comprising:

a) 55-70% by weight of ethanol and isopropanol;

b) 0.75-1% by weight of a vitamin B3 compound, which is niacinamide;

c) 3-10% by weight of propylene glycol;

d) 25-40% by weight of water;

and while the mass ratio of the vitamin B3 compound to propylene glycol is in the range from 1:2 to 1:20, and the viscosity of the composition is in the range from 0.5 Pa-s (500 cP) to 18 Pa-s (18000 cP) at 25°C.

The composition contains 0.05-0.8 wt.% thickening agent, which is a polymer containing monomers selected from acrylic acid, acrylates and compounds containing an acrylate group; and 0.1-0.13 wt.% of the main neutralizer, which is aminometipropanol.

The inventors have found that antimicrobial compositions that meet the above viscosity requirements are easily applied and spread over the skin, for example by rubbing.

The features and advantages of the invention will become apparent to those skilled in the art upon reading the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention may be used in any other aspect of the invention. The word containing means including, but not necessarily consisting of or formed from. In other words, the steps or options listed are not meant to be exhaustive. It should be noted that the examples, embodiments and figures below in the description are intended to explain the invention and are not intended to limit the invention to these examples as such.

Unless otherwise noted, numeric ranges expressed in x to y format are understood to include x and y. When specifying any range of values or amounts, any specific upper value or amount may be associated with any specific lower value or amount. Except for examples and comparative experiments, or if explicitly stated, all numbers are to be understood as modified by the word about. All percentages and ratios contained herein are by weight unless otherwise noted. The various features of the present invention mentioned in the individual sections above apply, if necessary, to other sections, mutatis mutandis. Therefore, the features specified in one section may be combined with the features specified in other sections, if necessary. Any section headings are added for convenience only and are not intended to limit disclosure in any way. The invention is not limited to the embodiments illustrated in the drawings. Accordingly, it should be understood that when features mentioned in claims are accompanied by reference numbers, such numerals are included solely for the purpose of enhancing the legibility of the claims and in no way limit the scope of the claims. The examples are intended to illustrate the invention and are not intended to limit the invention to these examples as such.

Detailed description of the invention

The first aspect of the invention relates to an antimicrobial composition for application to human skin, said composition comprising:

a) 55-70% by weight of ethanol and isopropanol;

b) 0.75-1% by weight of a vitamin B3 compound, which is niacinamide;

c) 3-10% by weight of propylene glycol;

d) 25-40% by weight of water; and while the mass ratio of niacinamide to propylene glycol is in the range from 1:2 to 1:20, and the viscosity of the composition is in the range from 0.5 Pa-s (500 cP) to 18 Pa-s (18000 cP) at 25 °C The composition contains 0.05-0.8 wt.% thickening agent, which is a polymer containing monomers selected from acrylic acid, acrylates and compounds containing an acrylate group; and 0.1-0.13 wt.% of the main neutralizer, while the main neutralizer is aminometipropanol.

As used herein, the term antimicrobial composition refers to a composition that is capable of killing bacteria or inhibiting their growth.

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As used herein, the term monohydric alcohols refers to alcohols containing a single hydroxyl group.

As used herein, the term vitamin B3 compound refers to vitamin B3, in particular niacinamide.

As used herein, the term polyols refers to alcohols containing multiple hydroxyl groups.

The term "viscosity" as used herein refers to the viscosity measured at 25°C with a Brookfield RV viscometer using spindle 4, 10 rpm for 30 seconds in a beaker, with the spindle probe immersed in the antimicrobial composition to the mark indicated on the spindle probe. . Several units are known to be used in the context of viscosity, but the most commonly used units are cP, Pa-s, and mPa-s, which are easily converted from one another using public resources such as textbooks, encyclopedias, and the Internet.

The term monophasic as used in this specification refers to compositions containing only one phase, such as an aqueous phase. For example, an emulsion contains two phases.

The antimicrobial composition according to the invention is preferably a leave-on composition. Preferably the composition is transparent.

The antimicrobial composition according to the invention is preferably a liquid at 20°C. The antimicrobial composition according to the invention is preferably monophasic.

The antimicrobial composition is preferably a liquid or thixotropic gel.

The weight ratio of vitamin B3 compound to propylene glycol in the composition according to the invention is preferably in the range from 1:3 to 1:15, even more preferably in the range from 1:4 to 1:10.

The viscosity of the composition according to the invention preferably ranges from 1 Pa-s (1000 cPa) to 15 Pa-s (15000 cP) at 25°C. More preferably, the viscosity range is from 4 Pa-s (4000 cP) to 12 Pa-s (12000 cP) at 25°C.

Preferably the composition contains 55-70 wt.% monohydric alcohols of ethanol and isopropanol.

Preferably, the antimicrobial composition contains up to 68% by weight of ethanol.

The antimicrobial composition preferably contains at least 0.75% by weight of the vitamin B3 compound.

In a preferred embodiment, the vitamin B3 compound is niacinamide.

In a preferred embodiment, the composition according to the invention contains 3-10% by weight of a propylene glycol polyol.

The antimicrobial composition preferably contains 25-40% by weight of water. More preferably, the composition contains 25-35 wt.% water, most preferably 25-30 wt.% water.

The composition preferably contains 0.05-0.8 wt.% thickening agent, most preferably 0.08-0.2 wt.% thickening agent.

The thickening agent in the composition according to the invention is preferably selected from homopolymers, copolymers, and combinations thereof, said homopolymers and copolymers containing monomers selected from acrylic acid, acrylates, acrylate group-containing compounds, and combinations thereof.

The composition preferably contains a basic neutralizer. The most preferred basic neutralizer is aminomethyl propanol, such as AMP-95.

In a preferred embodiment, the composition according to the invention contains from 0 to 15% by weight of optional ingredients such as chelating agents, colorants, perfumes, skin conditioners, vitamins other than vitamin B3, and combinations thereof.

The composition preferably contains skin conditioning agents, and these skin conditioning agents are preferably selected from silicones, siloxanes, and combinations thereof.

The composition preferably contains vitamins other than vitamin B3, and these vitamins are preferably selected from vitamin A, vitamin E, and combinations thereof. Even more preferably, the composition contains vitamin E.

A second aspect of the invention relates to the use of the antimicrobial composition described hereinbefore as an antiseptic, said use comprising applying the antimicrobial composition to human skin.

Hereinafter, the present invention will be described with reference to non-limiting examples.

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Examples

Example 1. Obtaining antimicrobial compositions.

Three antimicrobial compositions were obtained based on the formulations shown in table. 1.

Table 1

Ingredients Product 1 (wt%) Product A (wt%) Product B (wt%) ethanol 62 - 55 Isopropyl alcohol 3 - 10 Niacinamide 1 1 - Glycerol - - 1 propylene glycol 5 - - Carbomer® 980 0.325 - 0.350 AMP-95® OD - 0.147 Water Up to 100% Up to 100% Up to 100%

Product B corresponds to the antimicrobial composition currently available on the market.

Product 1 was obtained as follows.

First, the thickening agent Carbopol® 980 was slowly added to the water until a clear mixture was obtained. With continuous stirring of the mixture at a speed of 250 rpm, the following ingredients were sequentially added to the mixture: monohydric alcohols and a 6% aqueous solution of the main neutralizer AMP-95® (aminomethylpropanol). After addition of the basic neutralizer, the pH value and viscosity were measured and the pH value was adjusted to a pH value in the range of 6.5 to 7.5 by adding, if necessary, an additional amount of 6% aqueous solution of the basic AMP-95® neutralizer. Then, a clear pre-mixed aqueous solution of niacinamide and propylene glycol was added to the mixture with continuous stirring.

Product A was obtained by adding 1 wt.% niacinamide to 99 wt.% distilled water to obtain a solution of 1 wt.% niacinamide. Product B was obtained similarly to product 1.

Protocol for testing the antimicrobial efficacy of antimicrobial compositions.

The protocol has several stages, which are described below.

Pre-wash (7 days). Each test subject received a non-antimicrobial soap and was instructed to use only that soap for bathing and handwashing for 7 days and to refrain from using no-rinse products such as sunscreen or body lotion.

On day 8, three times an area of 12.25 cm ² (3.5 x 3.5 cm) was marked on one of the inner forearms using a marker pen and ruler. Then a circular area of 7.07±0.2 cm ² was marked with a surgical marker within each square on the indicated forearm using a template. One additional circular area of 7.07±0.2 cm ² was marked outside the squares on the forearm to which no products would be applied (untreated control). The distance between the squares was at least 2±0.2 cm.

After all test areas were identified, each test subject was asked to wash their forearms according to the following instructions.

a) Wet/dip non-antimicrobial soap for 10 s in sterile distilled water at 24±2°C.

b) Wet each forearm with sterile water (100±10 ml).

c) Rub the soap 5 times back and forth along the entire length of the forearm.

d) Add 5±1 ml of sterile water to the forearm and lather for 15 s.

e) Rinse the forearm with sterile water to completely remove the soap.

f) Remove excess water by drying with a dry sterile cloth.

mg of each antimicrobial composition to be tested was applied within the designated test areas and the composition was applied within the designated areas on the forearm. This application was carried out using gloves. The composition was applied to the area for 1-2 minutes. No product was applied to the untreated area. Product A was applied dropwise and then spread with a pipette tip.

After application of all antimicrobial compositions, test subjects were instructed to wait 6 hours ± 15 minutes in a controlled environment at 24 ± 2°C and 45 ± 10% relative humidity, while they were not to touch their forearms to any other surface or wet your forearms.

E. coli culture application and Cup-scrub sampling procedure.

15-30 minutes before the end of the waiting period, a sample of E. coli ATCC 10536 (1.0 x 10 ⁸ - 5.0 x 10 ⁸ cells/ml) was prepared in 10 mM sterile sodium phosphate buffer. The application of the E. coli culture was carried out under controlled conditions at 24±2° C. and 45±10% relative humidity.

6 h ± 15 min after application of the product, after vortexing, 10 µl (± 0.1 µl) of E. coli ATCC 10536 sample was added and spread evenly with a pipette tip inside the testing zones, leaving 0.2 cm from the mark, and start the timer. During application and removal of the sack

- 4 041341 tours E. coli subjects were asked to keep their forearms and hands on a table with palms up.

After 5 min ± 10 s of B. coli contact time on the forearm, a sterile cylinder (3 cm diameter) for sampling was placed on the E. coli application area. 1.5 ml of sterile sampling solution was pipetted into a cylinder. The bowl was firmly held against the surface of the skin to ensure that the sampled liquid did not leak from the sampling site.

The entire skin area inside the bowl was cleansed in all directions under moderate pressure for 60±5 s using a sterile blunt-ended shaft. After cleaning, all collected liquid was transferred by pipetting into a sterile labeled microcentrifuge or similar tube. The same process was repeated again for another 60±5 s and both samples were combined. After collecting the image, the area was blotted with clean paper towels.

The above E. coli application and sampling procedure was performed for all test areas. Simultaneously, samples were processed to count the number of live E. coli bacteria that survived exposure to the test areas using standard microbiological methods.

Upon completion of testing, subjects were asked to perform a 1-minute rinsing/rubbing of the forearm with swabs soaked in 70% Becton Dickinson isopropyl alcohol (BD) and air-dry, followed by a controlled 4-minute rinse with 4% chlorhexidine gluconate solution. Subjects were then asked to wash their forearms and palms with soap.

Results.

The number of bacteria surviving after exposure to the test areas is expressed as residual log survival. Thus, a residual log survival of 3 corresponds to 10 ³ surviving E. coli bacteria. The results are shown in table. 2 below.

table 2

Residual log survival Product 1 2.22 Product A 3.26 Product B 5.43

The viscosity of product 1 at 25°C was approximately 6 Pa-s (6000 cps). This was measured with a Brookfield RV viscometer using spindle 4 at 10 rpm for 30 seconds in a beaker while the spindle probe was immersed in the product to the mark indicated on the spindle probe.

Example 2

A similar experiment described in example 1 was carried out using antimicrobial compositions, which were obtained on the basis of the formulations shown in table. 3.

Table 3

Ingredients Product 2 (wt.%) Product C (wt %) ethanol 62 62 Isopropyl alcohol 3 3 Niacinamide 1 - propylene glycol 5 5 Carbomer® 980 0.325 0.325 AMP-95® 0.1 0.1 Water Up to 100% Up to 100%

Results.

The results are shown in the table below.

Table 4

Example 3

An experiment similar to that described above in example 1 was carried out using antimicrobial compositions, which were obtained on the basis of the formulations shown in table. 5.

Table 5

Ingredients Product 3 (wt.%) Product D (wt.%) ethanol 62 62 Isopropyl alcohol 3 3 Niacinamide 1 1 propylene glycol 5 5 Carbomer® 980 0.350 - AMP-95® 0.13 - Water Up to 100% Up to 100%

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Claims (9)

Results. The results are shown in Table 6 below. Table 6 Viscosity (cP) Residual log survival Product 3 12000 2.13 Product D 0 3.18 CLAIM 1. Antimicrobial composition for application to human skin, said composition contains: a) 55-70 wt.% ethanol and isopropanol; b) 0.75-1 wt% niacinamide; c) 3-10% by weight of propylene glycol; d) 25-40% by weight of water; and while the mass ratio of niacinamide to propylene glycol is in the range from 1:2 to 1:20, and the viscosity of the composition is in the range from 0.5 Pa-s (500 cP) to 18 Pa-s (18000 cP) at 25 °C; wherein the composition contains 0.05-0.8 wt.% thickening agent, which is a polymer containing monomers selected from acrylic acid, acrylates and compounds containing an acrylate group; And 0.1-0.13 wt.% of the main neutralizer, while the main neutralizer is aminometipropanol. 2. The antimicrobial composition of claim 1 wherein the weight ratio of niacinamide to propylene glycol is in the range of 1:3 to 1:15. 3. Antimicrobial composition according to claim 1 or 2, which contains 0.75 wt.% niacinamide. 4. Antimicrobial composition according to any one of pi. 1-3, which contains 25-30 wt.% water. 5. Antimicrobial composition according to any one of claims 1 to 4, which is liquid at 20°C. 6. Antimicrobial composition according to any one of claims 1 to 5, which is monophasic. 7. Antimicrobial composition according to any one of pi. 1-6, the viscosity of which is in the range from 1 Pa-s (1000 cP) to 15 Pa-s (15000 cP) at 25°C. 8. An antimicrobial composition according to any one of claims 1 to 7, which further comprises skin conditioning agents selected from silicones, siloxanes, and combinations thereof. 9. The use of an antimicrobial composition according to any one of pi. 1-8 as an antiseptic, said use comprising the application of an antimicrobial composition to human skin. Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky per., 2 -