WO2023154016A2

WO2023154016A2 - Method for increased skin penetration of active ingredients and salts thereof

Info

Publication number: WO2023154016A2
Application number: PCT/TR2022/050115
Authority: WO
Inventors: Gholamreza TAVOOSIDANA; Hamed Nikmaram
Original assignee: Dr Dermer Uk Kozmeti̇k Li̇mi̇ted Şi̇rketi̇
Priority date: 2022-02-11
Filing date: 2022-02-11
Publication date: 2023-08-17

Description

METHOD FOR INCREASED SKIN PENETRATION OF ACTIVE INGREDIENTS AND

SALTS THEREOF

FIELD

The present disclosure relates to a method for increasing skin penetration of active ingredients to the improvement of the skin. In particular, the invention relates to the locally utilized acid-base reaction which yields salts of acidic active ingredients and carbon dioxide gas, causing chemically and physically increased skin penetration, respectively.

BACKGROUND

Skin appearance has been an important concern of humans. The consumer concern is focused on the improvement of the skin using anti-ageing, anti-wrinkle and elasticity. The improvement of appearance using compositions including various ingredients has been used for a long time.

Skin is a highly defensive barrier in essence against the invasion of external pathogens, which makes it hard to penetrate. Therefore, it is quite challenging to safely and effectively deliver various active ingredients to deep skin layers.

Penetration enhancing technologies can be generally classified into chemical and physical methods. Chemical penetration enhancing methods involve the use of penetration enhancers (i.e., DMSO, azone and pyrrolidone, etc.), peptide penetration enhancers (i.e., skin penetration and cell entering peptide, SPACE peptide, etc.), nanoparticles systems (i.e., liposomes, microemulsions, micelles, carriers, etc.), and so on. The application of chemical methods is limited for some reasons, including poor penetration enhancing effects. On the other hand, physical penetration enhancing methods such as iontophoresis, ultrasound, electroporation, thermocautery, gas pressure, microneedles, etc. Despite their relatively high efficacy, they require special devices and, in some cases, are invasive. In the prior art, cosmetic masks provide the desirable method for the delivery of skin improvement ingredients, especially for facial skin. The cosmetic mask delivery systems are used for the face, chin, neck and different areas of the human body for delivering desired ingredients to the skin but there are still limitations.

U.S. Pat. App. Pub. No. 7879359 to Masaya Tanaka, describes a topical effervescent composition that makes it possible to prepare external carbon dioxide agent composition, when applied to the skin mucosa, exhibit potent cosmetic and medical effects and show quick expression of the effects.

Japan Pat. No. 6082382 discloses a cosmetic sheet product containing an acid-containing solution and a sheet substrate supporting a carbonate, using admixing a hydrophobically modified alkyl cellulose to the acid-containing solution and made it possible to provide a cosmetic sheet product that can uniformly and continuously generate carbon dioxide.

Korea Pat. No. 101037595. relates to a method for absorbing carbon dioxide into skin mucous membrane, comprising external gel in which sodium hydrogen carbonate is dissolved in a water- soluble gel is applied to the skin mucosa, the external gel application layer is covered by a nonwoven fabric having a citric acid coating layer such that carbon dioxide is absorbed in the skin mucosa.

Korea Pat. No. 101082365. Relates to a material and method enabling the absorption of carbon dioxide into skin mucosa by coating the skin with a serum containing citric acid and attaching the adhesion pad coated with a sheet of liquid containing sodium bicarbonate as the material contains lipase and protease.

None of the aforementioned patents in the prior art solved the problem to increase the penetration of active ingredients to the skin. It would thus be highly desirable if a method that develops to overcome such a limitation which can chemically and physically increase skin penetration of active ingredients. Such a method has not been disclosed in the prior art. It is therefore an object of the present invention to overcome limitations of previous efforts in the art to increase penetration of active compounds and carbon dioxide skin absorption more effectively.

SUMMARY

The disclosed invention relates to a method to increase skin penetration of active ingredients using a controlled acid-base reaction and comprises two different components: first an acidic viscous component and second a sheet component comprising one or more selected from carbonates and bicarbonates. In the first step, by applying the acidic viscous component to the skin, active ingredient(s) comprising one or a plurality of acidic active ingredients will start to affect the skin. The acidic ingredients of the first component promote exfoliation of the dead cells. After a preferred time, in the second step, the second component will be introduced completely on the applied first component and by pressing on it, the chemical acid-base reaction occurs. In this manner, the excess acidic ingredients of the first component react with the carbonate and/or bicarbonate of the second component which causes neutralization of excess acidic ingredients and yields salts and carbon dioxide. The produced salts of active ingredients have benefits to the skin and have more stability, water solubility, and bioavailability. The locally produced carbon dioxide penetrates into the skin which causes increased skin penetration of active ingredients and the mentioned produced salts thereof. While carbon dioxide penetration to the skin causes increased blood circulation and hence increased oxygen levels.

Furthermore, to overcome the limitations of the prior art, to achieve more efficient levels of increased skin penetration, the sheet component comprises a polymerized layer of latex or the like on one side of the sheet component with the desired % of weight, as a barrier to conduct active ingredients, produced salts and carbon dioxide to the skin.

The sheet component also comprises crystals of alumina, silicon, carbonate, bicarbonate, etc. While pressing the sheet component on the skin, the crystals will make micron-sized abrasion of the epidermis while the sheet part reacts with the acidic viscous component causing more effective penetration of the viscous component's active ingredients, salts thereof and carbon dioxide. In a preferred embodiment of this invention, in the first step, crystals of carbonate and/or bicarbonate material solely or in combination with other crystal materials are used as skin polish paste to gently peel and dermabrasion the skin by scrubbing, then in the second step the acidic viscous component will be daubed on the applied polish paste on the skin and starts to react with carbonate and/or bicarbonate ingredients of the polishing paste and also affects the skin. In the third step, the sheet component comprising one or more selected from carbonates and bicarbonates will be placed on them and the acidic ingredients will be neutralized completely and the result will be plenty of salts and carbon dioxide.

The invention related to a method is useful for improving blood circulation in the skin, exfoliating, hydration, whitening, elasticity, improving texture, promoting healing, stimulating collagen synthesis, deep moisture retention, and rejuvenating the skin.

BRIEF DESCRIPTION OF DRAWINGS

Exemplary embodiments are illustrated in referenced figures of the drawings. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive. These embodiments are not to be interpreted in a limiting manner, such as limiting the claims appended hereto.

Figure- 1 shows a two-dimensional cross-section depiction of the sheet component comprising a barrier layer and impregnated crystals.

Figure-2a and 2b are two flowcharts depicting methods for the increased skin penetration of active ingredients and salts thereof in two and three steps, according to particular embodiments of the invention.

DETAILED DESCRIPTION

The following detailed description has presented a method for locally controlled acid-base reaction to topically produce salts and carbon dioxide in a manner to chemically and physically increase penetration of active ingredients and the produced salts thereof with carbon dioxide to the skin. By the disclosed method, cosmetic products with antiaging, anti-wrinkle benefits and useful for improving blood circulation in the skin, exfoliating, hydration, whitening, elasticity, improving texture, promoting healing, stimulating collagen synthesis, deep moisture retention and rejuvenation of the skin can be developed. By this invention, different skincare products such as gel-like, foam, cream, lotion or any other liquid-based viscous material for the improvement of different types of skin can be developed.

The disclosed method comprises a skin polishing paste comprising crystals of carbonates, an acidic viscous component comprising the desired target active ingredients, and a sheet component.

Figure- 1 shows a two-dimensional cross-section of the sheet component comprising fibre texture (11) having one or more selected from carbonates and bicarbonates that has a barrier of polymerized material (12) to direct the produced salt and gas into the skin and is impregnated with crystals (13) to have micron-sized dermabrasion effect on the skin.

Figure-2a shows a two-step method 101 comprising the acidic viscous component and the sheet component, and Figure-2b shows a three-step method 102 comprising the polish paste, the acidic viscous component and the sheet component.

In an embodiment, the invented method with two steps comprises two different components: first, an acidic viscous component comprising target active ingredient(s) and second, a sheet component comprising one or more selected from carbonates and bicarbonates. The applied first component on the skin reacts with the second component when introduced. This intended local acid-base reaction neutralizes the excess acids of the first component and yields salts and carbon dioxide.

In the first step, by applying the first component to the skin, active ingredients comprising one or a plurality of alpha-hydroxy acids, beta-hydroxy acids, citric acid, azelaic acid, ascorbic acid, hyaluronic acid, tocopherol, vitamin E, vitamin A etc. will start to affect the skin. The acidic ingredients of the first component promote exfoliation of the dead cells. After a preferred time, in the second step, the second component will be introduced completely on the applied first component and by pressing on it, the chemical acid-base reaction occurs. In this manner, the excess acidic ingredients of the first component react with the carbonates and/or bicarbonates of the second component which causes neutralization of excess acidic ingredients and yields salts and carbon dioxide. The produced salts of active ingredients have benefits to the skin and have more stability, water solubility, and bioavailability, thus having better skin penetration. The locally produced carbon dioxide penetrates into the skin which causes increased skin penetration of active ingredients and the mentioned produced salts thereof. While carbon dioxide penetration to the skin causes increased blood circulation and hence increased oxygen levels. After a preferred time, the sheet component is pulled away from the face or area and is washed with warm water to remove deep pore cleaning and skin debris removal function.

The viscous component comprises at least an acid, water, thickener, and preferred active ingredient(s). The viscous component can be produced by a known method and the production method is not particularly limited.

A way to prepare the viscous component is by adding one or a plurality of hydrogel -forming raw material to the acid and water. The raw material for forming the viscous component comprises natural polymers, Semi-synthetic polymers, and Synthetic polymers and is not particularly limited.

As the thickener used for the viscous component, at least one selected from the group consisting of natural polymers, semi-synthetic polymers, synthetic polymers, and inorganic materials is used.

In the composition for preparing an acidic viscous component, water is not specifically limited as long as it can be used for conventional cosmetics, medical supplies, etc., such as distilled water, membrane filtrated water, and ion-exchanged water, for example.

One or a plurality of the organic and inorganic water-soluble acid(s) can be used in the said acidic viscous component. The organic acid(s) comprising dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid, and terephthalic acid; acidic amino acids such as glutamic acid and aspartic acid; and hydroxy acids such as glycolic acid, malic acid, tartaric acid, itatartaric acid, citric acid, isocitric acid, lactic acid, hydroxyacrylic acid , oxybutyric acid, glyceric acid, tartronic acid, salicylic acid, gallic acid, tropic acid, ascorbic acid, and gluconic acid and the inorganic acid(s) comprising phosphoric acid, potassium dihydrogen phosphate, sodium dihydrogen phosphate, sodium sulfite, potassium sulfite, sodium pyrosulfite, potassium pyrosulfite, acidic sodium hexametaphosphate, acidic potassium hexametaphosphate, acidic sodium pyrophosphate, acidic potassium pyrophosphate, and sulfamic acid.

The preferred target active ingredients can be one or a plurality of acidic active ingredients comprising alpha-hydroxy acids, beta-hydroxy acids, citric acid, azelaic acid, salicylic acid, ascorbic acid, hyaluronic acid, tocopherol, vitamin E, vitamin A, etc.

In the composition of the acidic viscous component, Herbal extract and essences, essential oils of any plant materials and fragrances can be comprised.

Examples of the plant-derived polymer included in the natural polymer to be used as a thickener in the invention are gum arabic, xanthan gum, carrageenan, galactan, agar, quince seed gum, guar gum, tragacanth gum, pectin, mannan, locust bean gum, wheat starch, rice starch, corn starch, potato starch and the like.

Examples of the cellulosic polymer included in the semi-synthetic polymer to be used as a thickener in the invention are ethyl cellulose, carboxymethyl cellulose and salts thereof, carboxymethylethyl cellulose and salts thereof, carboxymethyl starch and salts thereof, croscarmellose and salts thereof, crystalline cellulose, cellulose acetate, cellulose acetate phthalate, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxypropylmethyl cellulose phthalate, powdered cellulose, methyl cellulose, methylhydroxypropyl cellulose and the like.

Examples of the starch polymer included in the semi-synthetic polymer to be used as a thickener in the invention are pregelatinized starch, partially pregelatinized starch, carboxymethyl starch, dextrin, methyl starch and the like. The disclosed invention also relates to a method to use liposomal or nanoliposome and emulsion or nanoemulsion as an efficient carrier for active ingredients to increase penetration to the skin. The said liposomal or nanoliposome and emulsion or nanoemulsion are trapped in the viscous component and promote more effective skin penetration of active ingredients by the method described in this invention.

The sheet component is provided by textures comprising micro and/or nano fibre polymers, nonwoven fabric, cloth or the like which are prepared in a way that contains one or more selected from carbonates and bicarbonates and also can contain one or a plurality of bases components and/or different components such as xanthan gum or the like. One side of the sheet component also comprises a polymerized barrier layer of latex or other semi-permeable or impermeable polymers with the desired weight % of the sheet component. The mentioned barrier prevents CO2 diffusion into the atmosphere and directs the produced salts and carbon dioxide to the skin. The thickness of the base material is usually 0.01 to 1 mm.

The sheet component comprises at least one or more selected from carbonates and bicarbonates and can also contain one or a plurality of water-soluble bases.

The sheet can be prepared by different loading methods such as soaking in liquid or spraying of one or more selected from carbonates and bicarbonates and/or different components then drying by airflow or any mild drying methods. The production method of the sheet component does not affect the novelty of this invention.

The sheet component is impregnated with crystal materials comprising one or more selected from carbonates and bicarbonates, alumina, silicon, etc. crystals. While pressing the sheet component on the skin, the crystals will make micron-sized abrasion of the epidermis causing more effective skin penetration by this invented method. The size of the crystals should be enough to be sensible on the skin and can vary from 100 microns to 2 millimetres and the mentioned crystals are impregnated in the texture of the sheet layer or are held by the aforementioned polymerized barrier layer of sheet component. In another embodiment of this invention, carboxy polish is disclosed to achieve more skin penetration of active ingredients, salts thereof and carbon dioxide. Carboxy polish refers to a method for skin polishing by a polishing paste containing at least one carbonate or bicarbonate crystal prior to applying the acidic viscous component and then sheet component. In this embodiment, the disclosed method for the increased skin penetration of active ingredients and salts thereof comprises three steps: in the first step, crystals of at least one or more selected from carbonates and bicarbonates solely or in combination with other crystal materials comprising alumina, silicon, etc. are used as skin polish paste to gently peel and dermabrasion of the skin by scrubbing, then in the second step the acidic viscous component will be daubed on the applied polish paste on the skin and starts to react with aforementioned carbonate and/or bicarbonates and also affects the skin for a preferred period of time. In the third step, the sheet component comprising one or more selected from carbonates and bicarbonates will be placed on them and the acidic ingredients of the viscous component will be neutralized completely and the yield will be plenty of salts and carbon dioxide. The carbon dioxide penetrates the skin while promoting skin penetration of acidic active ingredients and salts thereof.

The composition of the carboxy polish paste component comprises at least one carbonate or bicarbonate crystals, water, a thickener and can also have other alkaline or basic skin exfoliating materials or buffers. The paste component can be produced by a known method and the production method is not particularly limited. The raw material for forming polish paste comprises natural polymers, Semi-synthetic polymers, and Synthetic polymers and is not particularly limited.

As the thickener used for the paste component, at least one selected from the group consisting of natural polymers, semi-synthetic polymers, synthetic polymers, and inorganic materials is used.

The crystal used for the paste component comprises at least one or more selected from carbonate and bicarbonate crystals and can be in combination with any crystal materials that can have an abrasion effect on the skin such as alumina, silicon, clay, etc. The size of crystals can be from 100 microns to 2 millimetres, the size which is sensible on the skin is preferred. EXAMPLES

The following examples are presented to illustrate presently preferred practice thereof and they are not intended to limit the scope of the invention. All quantities are in weight %.

Example 1

Sodium bicarbonate containing fiber or texture is prepared by flowing viscous sodium bicarbonate composition through fiber or texture. The composition is sodium bicarbonate and xanthan gum. The viscous composition is dried by cold or warm airflow conditions. The thickness of the mask should be suitable for use. If necessary, suitable ingredients and medicinal substances may be added. The composition contains 10 to 90 % sodium bicarbonate in viscous solution. The device was prepared by applying viscous liquid including sodium bicarbonate and xanthan gum to mask, cut into a square having different parts.

The acid-containing gel-like composition is viscous each prepared by mixing a suitable acid or/and suitable ingredients. The viscous gel-like aqueous can be prepared by mixing/homogenizing 3 % sodium alginate, 5 % carboxymethyl starch, 10 % carboxymethyl cellulose, 10 % glycerin, 11 % xanthan gum, 4 % propylene glycol, 3 % CaC12, 0.1 to 0.3 % v/w methylparaben and 5 % of suitable the different acid such as acetic, lactic and succinate or combination of.

Example 2

The obtained gel-like composition in example 1 can be used with a suitable combination of ingredients such as 3.2 % vitamin A, 3.5 %vitamin B, 3 % vitamin E, 2 % vitamin D, and any other compatible ingredients.

Example 3

The obtained gel-like composition in example 1 can be used with a suitable one or a combination of ingredients such as 10 % glycolic acid or 5 % azelaic acid or 5 % vitamin C or 10 % tocopherol or 3 % vitamin E or 20 % hyaluronic acid or and any other compatible ingredients Example 4

Apply gel-like composition obtained as a thick layer with a thickness of about 1 to 3mm on the face or different areas of the body, and apply the mask (filter or texture part) on the gel-like film to contact directly with a gel-like composition and compressed mildly. Gently press the mask to absorb gas by the skin. The mask separates after 10 to 20 minutes from the skin and the skin is washed by water.

Example 5

A sodium bicarbonate polish paste contains 60 % sodium bicarbonate, 5 % glycerin and 3 % carboxy methyl cellulose as a thick layer with a thickness of about 1 to 2 mm on the face or different areas of the body and star to scrub the skin. Then the gel-like acidic component containing citric acid and other acidic active ingredients will be applied to the skin and react with sodium bicarbonate polish paste. After 5 minute, the sheet component will be placed on the skin and more effectively the acid base reaction occurs and more amounts of salts and carbon dioxide will be produced.

Claims

1) A method to locally controlled acid-base reaction to topically produce salts and carbon dioxide in a manner to chemically and physically increase skin penetration of active ingredients and the produced salts thereof characterized in that it comprises two components: a. An acidic viscous component comprising target active ingredient(s) b. A sheet component comprising one or more selected from carbonates and bicarbonates, a barrier layer and impregnated crystals. comprising two steps: a. In the first step, by applying the acidic viscous component to the skin, target active ingredient(s) will start to affect the skin in a preferred time. b. In the second step, the sheet component will be introduced and pressed completely on the applied acidic viscous component on the skin to neutralize the excess of acids and to produce salts thereof and carbon dioxide to increase the skin penetration while causing dermabrasion by sheet component's crystals.

2) A method to locally controlled acid-base reaction to topically produce salts and carbon dioxide in a manner to chemically and physically increase skin penetration of active ingredients and the produced salts thereof characterized in that it comprises three components: a. a skin polishing paste comprising at least one carbonate or bicarbonate crystals. b. acidic viscous component comprising target active ingredient(s). c. sheet component comprising one or more selected from carbonates and bicarbonates, a barrier layer and impregnated crystals. comprising three steps: a. In the first step, the polishing paste is used as skin polish to gently peel and dermabrasion the skin by scrubbing b. In the second step, the acidic viscous component will be daubed on the applied polish paste on the skin and starts to react with carbonate and/or bicarbonates of polishing paste and also affects the skin for a preferred period of time. c. In the third step, the sheet component will be introduced and pressed completely on the applied polishing paste and acidic viscous component on the skin, the acidic ingredients of the viscous component will be neutralized completely and the yield will be plenty of salts and carbon dioxide to increase the skin penetration while causing dermabrasion by sheet component's crystals.

3) The method according to claim 1 or 2 characterized in that, wherein the viscous component comprises at least an acid, water, thickener, and preferred active ingredient(s) and can be produced by any method.

4) The method according to claim 1 or 2 characterized in that, wherein the active ingredients in the acidic viscous component are one or a plurality of alpha-hydroxy acids, beta-hydroxy acids, citric acid, azelaic acid, ascorbic acid, hyaluronic acid, tocopherol, vitamin E, vitamin A etc.

5) The method according to claim 1 or 2 characterized in that, wherein the thickener used for the viscous component, comprises at least one selected from the group consisting of natural polymers, semi- synthetic polymers, synthetic polymers, and inorganic materials is used.

6) The method according to claim 1 or 2 characterized in that, wherein the composition of the acidic viscous component comprises, Herbal extract and essences, essential oils of any plant materials and fragrances.

7) The method according to claim 1 or 2 characterized in that, wherein the liposomal or nanoliposome and emulsion or nanoemulsion can be used as an efficient carrier for active ingredients to increase penetration to the skin.

8) The method according to claim 1 or 2 characterized in that, wherein the sheet component is provided by textures comprising micro and/or nano fibre polymers, nonwoven fabric, cloth or the like which are prepared in a way that contains one or more selected from carbonates and bicarbonates and also can contain one or a plurality of bases components and/or different components such as xanthan gum or the like and the thickness of the base material is usually 0.01 to 1 mm. 9) The method according to claim 1 or 2 characterized in that, wherein one side of the sheet component also comprises a polymerized barrier layer of latex, resin, polyethylene or other semi- permeable or impermeable polymers with the desired weight % of the sheet component.

10) The method according to claim 1 or 2 characterized in that, wherein the sheet component comprises at least one or more selected from carbonates and bicarbonates and can also contain one or a plurality of water-soluble bases.

11) The method according to claim 1 or 2 characterized in that, wherein the sheet component is impregnated with crystal materials comprising one or more selected from carbonates and bicarbonates, alumina, silicon, etc. crystals to make micron-sized abrasion of the epidermis and the size of the crystals can vary from 100 microns to 2 millimetres.

12) The method according to claim 1 or 2 characterized in that, wherein the acidic viscous component can be different skincare products such as gel-like, foam, cream, lotion or any other liquid-based viscous material for the improvement of different types of skin.

13) The method according to claim 2 characterized in that, wherein the composition of the polish paste component comprises at least one carbonate or bicarbonate crystals, water, a thickener and can also have other alkaline or basic skin exfoliating materials or buffers.

14) The method according to claim 2 characterized in that, wherein the crystal used for the paste component comprises at least one or more selected from carbonate and bicarbonate crystals and can be in combination with any crystal materials that can have an abrasion effect on the skin such as alumina, silicon, clay, wherein the size of crystals can vary from 100 microns to 2 millimetres.