Composition for the controlled release of an active ingredient

Abstract

A topical film-forming composition capable of efficiently delivering an active ingredient to the keratin surface in a sustained-release manner includes a combination of an acrylate copolymer and an acrylate / VA copolymer, and a combination of 1,3-propanediol and glycerin. The size of the pores formed in the dry film can be controlled or finely adjusted.

Description

Technical Field

[0001] The present invention belongs to the field of topical formulations for the keratin surface. More particularly, the present invention relates to film-forming compositions capable of efficiently delivering an active ingredient to the skin in a controlled release manner.

Background Art

[0002] In co-owned applications US15 / 632903 (now US Patent No. 11,103,439), US15 / 906372 (now US Patent No. 10,813,874), US17 / 029147, US17 / 176527, US16 / 816995, US16 / 197858, US16 / 381806 (now US Patent No. 10,507,175), US16 / 267441 (now US Patent No. 10,980,717), US17 / 189768, and US16 / 827876 (now US Patent No. 11,129,788) (all of which are incorporated herein by reference in their entirety), the applicant has disclosed certain combinations of acrylate / VA copolymers and acrylate copolymers in an aqueous base, as well as various useful properties of these combinations depending on the application and presence of certain other components. These compositions are water-based, but when applied to the skin surface, they dry to form a transparent, flexible, and comfortable film.

[0003] The present inventors have disclosed in US16 / 267441 (currently US Patent No. 10,980,717) an ethanol-reduced fragrance composition containing about 50 to 60% water, about 3 to 30% fragrance components, about 4.5 to 18.5% acrylate / VA copolymer, about 0.25 to 1.0% acrylate copolymer (where the weight ratio of acrylate / VA copolymer to acrylate copolymer is in the range of 10:1 to 30:1), and one or more plasticizers, where the plasticizer may be up to 4.5% glycol (butanediol, propanediol, pentylene glycol) or up to 5% alcohol, provided that the weight ratio of acrylate / VA copolymer to total plasticizer is in the range of 1:1 to 10:1. It has been pointed out that generally, the more plasticizer in the aqueous phase, the larger the size of the surface pores formed in the film, which is the dried product of the acrylate / VA copolymer-acrylate copolymer composition. Controlling this pore size is the key to achieving controlled release of the fragrance as a function of time. Compared with the present invention, what the present inventors should note is that the diffusion of fragrance molecules from the fragrance components in the pores of the dried film to the atmosphere is not the same as the release of active ingredients from the pores of the dried film to the skin, which is promoted by osmotic pressure.

[0004] In US16 / 827876 (now US Patent No. 11,129,788), the inventors disclosed a sprayable film-forming composition containing about 70-85% water, about 4.7-14% acrylate / VA copolymer, about 0.05-2.5% acrylate copolymer, and about 1-5% plasticizer (which can be any one of glycerin, propanediol, butylene glycol, or a combination thereof) based on the total weight of the composition. It was reported that the weight ratio of the acrylate / VA copolymer to the acrylate copolymer is in the range of 1.8:1 to 280:1, preferably 10:1 to 100:1, more preferably 10:1 to 30:1, and most preferably 20:1. It was reported that the plasticizer affects the porosity of the dried film. It was also reported that when these compositions are applied to a substrate and dried, the dried film has an average porosity between 0.25 μm and 3.0 μm. Furthermore, it was pointed out that due to this pore size, the compositions disclosed therein are useful as delivery vehicles for active ingredients. Specifically, a pore size of 0.9 μm to 2.5 μm is particularly useful for the controlled or sustained release of active ingredients. Examples of active ingredients that may be incorporated into the aqueous or oil phase were disclosed.

[0005] None of the aforementioned references disclose a more robust delivery system for the controlled release of the following active substances.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

[0007] The main object of the present invention is to provide a more robust delivery system for the controlled release of active substances that is comfortable on the skin for a long time, less affected by contact movement, and can be easily removed by rubbing in water. [Means for Solving the Problems]

[0008] The topical composition for the controlled release of the active ingredient contains a combination of 20% to 60% by weight of acrylate copolymer and acrylate / VA copolymer, and the weight ratio of acrylate / VA copolymer to acrylate copolymer is in the range of 10:1 to 30:1, preferably 15:1 to 25:1, more preferably about 20:1. The composition also contains a combination of 5.5% to 10%, preferably 6% to 7% of 1,3-propanediol and glycerin, and the weight ratio of 1,3-propanediol to glycerin is in the range of about 1:1 to about 4:1, preferably about 2:1 to about 3:1. When these compositions are applied to a substrate, such as a keratin surface, and dried, the dried film has an average porosity between about 0.1 μm and about 10 μm. [Modes for Carrying Out the Invention]

[0009] Unless otherwise indicated or explicitly suggested during operation or in the comparative examples, all numbers in this description that imply amounts or ratios of materials, or conditions of reaction, physical properties of materials, and / or use should be understood to be modified by the term "about". All amounts are expressed as weight percentages of the final composition unless otherwise specified.

[0010] Throughout this specification, "film former" or the like means a polymer that leaves a film on the applied substrate after, for example, the solvent with the film former has evaporated, been absorbed into, and / or dissipated on the substrate.

[0011] "Comprise" means that a series of elements cannot be limited to those explicitly detailed.

[0012] Acrylate / VA copolymer The first main component of the present invention is an acrylate / VA copolymer (INCI name), C 15 H 26 O4, also known as vinyl acetate or 2-ethylhexyl prop-2-enoate (IUPAC name), CAS number 25067-02-1. For detailed information, refer to CID = 168269 in the PubChem Compound Database.

[0013]

Chemical formula

[0014] In cosmetics, this adhesive material often acts as a binder, film former, adhesive, and / or hair fixative. When introduced into an aqueous cosmetic system, the acrylate / VA copolymer can provide a film on the skin or hair. A pure acrylate / VA copolymer film can be decomposed and removed from the surface by rinsing with water at about 38 °C or higher, but it is characterized by temperature dependence that maintains its integrity at temperatures below normal skin temperature (i.e., 36.5 - 37.5 °C).

[0015] The acrylate / VA copolymer is commercially available, for example, as Vinysol 2140L from Daito Kasei Co., Ltd. Vinysol 2140L is a 46.6% aqueous mixture of the acrylate / VA copolymer. Vinysol 2140L has a pH of 4.5, a viscosity of 2,000 mPa·s, and a calculated glass transition temperature (T ag ) of -9°C. On the other hand, the film shows an elongation at break of 1,200% and a breaking strength of 1.2 MPa (when stretched to a thickness of 0.1 mm). The acrylate / VA copolymer by itself is somewhat too hard to be acceptable to consumers.

[0016] Acrylate copolymer To address this problem of being very hard, the acrylate / VA copolymer was combined with an acrylate copolymer, C 14 H 22 O6. This is also known as ethyl prop-2-enoate, methyl 2-methylprop-2-enoate or 2-methylprop-2-enoic acid (IUPAC name), CAS number 25133-97-5. This acrylate copolymer has a lower T g than the acrylate / VA copolymer. For detailed information, refer to CID=168299 in the PubChem Compound Database. In various types of cosmetic formulations, acrylate copolymers have a wide variety of uses including film formers, hair fixatives, binders, and suspending agents, viscosity enhancers, antistatic agents, and adhesives.

[0017] The acrylate copolymer is commercially available, for example, as Daitosol 5000AD from Daito Kasei Kogyo Co., Ltd. Daitosol 5000AD is a 50% aqueous mixture of the acrylate copolymer. Daitosol 5000AD is reported to have a pH of 5.5 - 7.5, a viscosity of 50 - 100 mPa·s, and a glass transition temperature (T g ) of about -14°C.

[0018] The topical aqueous composition of the present invention contains a film-forming agent comprising an acrylate / VA copolymer and an acrylate copolymer in a weight ratio of 10:1 to 30:1, and the combined weight of the acrylate / VA copolymer and the acrylate copolymer is 20% to 60% of the total composition weight. Preferably, the weight ratio of the acrylate / VA copolymer to the acrylate copolymer is about 15:1 to 25:1, more preferably about 20:1, for example 19:1 to 21:1. For example, one embodiment of a useful composition contains 40% acrylate / VA copolymer and 2% acrylate copolymer.

[0019] Porosity regulator As already described, the composition according to the invention is water-based, but when applied to the skin it dries to form a porous film. As the film dries, the molecules of the active ingredient(s) accumulate within the pores of the dry film, preventing a significant amount of the active ingredient(s) from aggregating. Thereby, the particle size of the active ingredient(s) remains small enough to reliably penetrate the skin. Thereafter, under the action of osmotic pressure, these active molecules are released from the pores of the film into the skin.

[0020] However, generally, there is a need to further adjust the porosity so that the release of the incorporated molecules is not too slow or too fast. If the release is too slow, the active ingredient may not produce the desired effect on the skin. If the release is too fast, the active ingredient is likely to irritate the skin. The inventors have discovered a method of controlling the release of the active material from the film described above by adjusting the porosity of the film without impairing many useful properties of the film, particularly its breathability. By breathability, the inventors mean the air permeability of the dry film. Typically, it has been observed that the compositions of the present invention, when dried, allow air to pass through even at ambient pressures as low as about 1 psi. Maintaining the breathability of the dry film is important for the comfort of the user.

[0021] Porosity (or pore size) is controlled by including a porosity modifier in the composition. The porosity modifier contains 1,3-propanediol and glycerin in a weight ratio of about 1:1 to 4:1, and the combined weight of 1,3-propanediol and glycerin contains about 5.5% to 10% of the total composition weight. Preferably, the weight ratio of 1,3-propanediol to glycerin is about 1:1 to 3:1, more preferably about 2:1 to 2.5:1. Preferably, the combined weight of 1,3-propanediol and glycerin is in the range of about 5.5% to about 7%, more preferably about 6%, based on the total weight of the composition. For example, a total of 6% porosity modifier consisting of a combination of 4% 1,3-propanediol and 2% glycerin meets this requirement.

[0022] As described above, the inventors have observed that the pore size of the dry film can be controlled or finely adjusted with a combination of 1,3-propanediol and glycerin as defined above. Generally, a large (small) amount of the porosity regulator results in a film with large (small) pores on average. Using the concentrations disclosed above, it is possible to create a film with an average pore size in the range of about 0.1 μm to 10 μm, and the range of the average pore size can be finely adjusted. For example, it is possible to create a polymer film in which 75% to 90% of the pore size is within about 1 μm, and the remaining 10% to 25% is above and below this range. The inventors have made a polymer film according to the present invention, for example, in which about 80% of the pore size is in the range of 1.75 to 2.75 μm, about 10% is in the range of 1.00 to 1.75 μm, and about 10% is in the range of 2.75 to 3.75 μm. Larger pores may release the active ingredient faster than ideal, but the amount of the active ingredient released is relatively small and is less likely to cause irritation. Since all or most of the active substances are trapped in pores of similar size (within about 1 μm), the release of most of the active substances can be controlled. If the distribution width of the pore size is too wide, it is less likely to achieve controlled release suitable for the local personal care market. In the composition of the present invention, it is preferable that 75% to 90% of the pore size in the dry polymer film is within about 2 μm, more preferably within about 1.5 μm, and most preferably within about 1.0 μm.

[0023] Active ingredient The active ingredients may be incorporated into the aqueous or oily phase (if present). Non-limiting examples of hydrophilic (water-soluble) actives include algae extract, alpinia speciosa leaf extract, Alteromonas fermentation extract, ascorbyl glucoside (AA2G), citrullus lanatus (watermelon) fruit extract, crataegus monogyna (hawthorn) flower extract, hyaluronic acid, hydrolyzed yeast protein, Lactobacillus fermentation broth, matricaria (chamomile) extract, lens esculenta (lentil) fruit extract, paeonia suffruticosa (peony) root extract, panthenol, pyrus malus (apple) fruit extract, and saccharum officinarum extract. Non-limiting examples of hydrophobic (oil-soluble) actives include Anthemis nobilis oil, BHT (dibutylhydroxytoluene), caffeine, coconut oil, salicylic acid, vitamin A, ascorbyl tetrahydroxydecyl, and tocopheryl acetate. The combined concentration of all active ingredients typically varies between 0.0001 wt% and about 10 wt% of the composition.

[0024] Water The composition of the present invention is water-soluble and typically contains at least about 25 wt% water of the total composition. It is preferred that the total amount of water is at least 50%. This amount of water is the water from all sources, such as from Vinysol 2140L and Daitosol 5000AD.

[0025] Optional ingredients The composition of the present invention may optionally contain a preservative, typically at most about 2% by weight of the composition. Similarly, a viscosity modifier and / or a pH adjuster may optionally be used, typically at a level of less than 1% by weight of the composition, to make a product acceptable to the consumer. Preservatives, viscosity modifiers, and pH adjusters at this level do not appear to adversely affect the controlled release of the active substance from the dry polymer film.

[0026] Some preferred embodiments of the present invention are single-phase aqueous compositions having little or no oil or silicone. However, in other preferred embodiments, the composition is a lightly emulsified oil-in-water emulsion. The emulsion embodiments are useful when the composition is used to deliver at least one oil-soluble active substance (e.g., vitamin E acetate) to the keratin surface. The emulsion embodiments include one or more surfactants or emulsifiers having an HLB between 8 and 12, and may be between 2% or less of the total composition, typically between 0.01% and 2% of the total composition.

[0027] Agents that significantly interfere with the structure of the dry film may adversely affect the controlled release of the active substance from the dry polymer film. Therefore, the composition of the present invention preferably contains a structuring agent in a total amount of 0.5% or less, for example, a structuring agent in an amount of 0.0001% to 0.5%, such as Carbopol (registered trademark), wax, clay (e.g., bentonite) or stearic acid. More preferably, the composition of the present invention contains a structuring agent in a total amount of 0.001% or less. Most preferably, the composition of the present invention contains no structuring agent at all. A useful exception to this rule is sodium stearate. Unlike many structuring agents, sodium stearate is partially hydrophilic, thereby making it suitable for aqueous systems. Although sodium stearate is partially hydrophobic, its use does not seem to interfere with the objectives of the present invention. Thus, when a structuring agent may be required, sodium stearate is particularly useful in embodiments of the present invention. Sodium stearate can be used as a structuring agent in an amount of 0.0001% to 4% by weight of the total composition. Exceeding this amount may begin to disrupt the acrylic bond strength, which may adversely affect the controlled release of the active substance from the dry polymer film.

[0028] What the inventors should note here is that polyurethane not only tends to make the composition of the present invention very hard, but also adversely affects the controlled release of the active substance from the dry polymer film. Therefore, the film-forming composition of the present invention contains polyurethane in an amount of 0.5% or less, for example, 0.0001% to 0.5%. More preferably, the composition of the present invention does not contain polyurethane.

[0029] Delivery of the active substance When the composition according to the present invention is applied to a substrate and dried, the dry film has pores in which molecules of the active ingredient accumulate. Subsequently, the osmotic pressure drives the active molecules out of the pores of the film and into the skin.

[0030] In practice, the porosity of the dry film is selected based on the molecular weight of the active material and the desired release rate. Generally, the larger the molecular weight of the active ingredient, the larger the pore size required to allow accumulation of the active ingredient molecules within the pores of the film. The release rate is selected based on the tendency of the active substance to irritate the skin relative to the intended benefit. A slow release rate (low porosity) may be required to avoid unacceptable levels of irritation, but if the release rate is too slow, it may not provide a distinct benefit. Through typical trial and error, films with specific pore size distributions and release rates can be obtained for each specific active substance.

[0031] For example, a useful composition according to the present invention in which the active ingredient is glycolic acid (hydrophilic with a molecular weight of 76.05 g / mol) had an average pore size of about 1.5 μm. Another composition according to the present invention in which the active ingredient is salicylic acid (hydrophobic with a molecular weight of 138 g / mol) had a useful average pore size in the range of about 1.6 μm to about 3.0 μm. More generally, useful average pore sizes at molecular weights in the range of about 30 to about 90 g / mol can be in the range of about 0.1 μm to about 1.5 μm. Useful average pore sizes at molecular weights in the range of 90 to 300 g / mol can be in the range of about 1.5 μm to about 3.0 μm. Moreover, the topical compositions according to the present invention exhibit controlled release of the active ingredient such that when the pore size of the dry film is adjusted based on the molecular weight of the active molecule, skin inflammation or irritation is significantly reduced or eliminated. The following examples show the controlled release of salicylic acid from a composition containing 1% salicylic acid according to the present invention.

Example

[0032]

Table 1

[0033]

Table 2

[0034]

Table 3

[0035] The skin of Control 2 and the blank serves as the baseline for fluorescence measurement. As shown in Table 3, there was little movement of salicylic acid from Control 2. Control 2 without the porosity modifier (i.e., the combination of 1,3-propanediol and glycerin) is a delivery system that has no effect on the active ingredient.

[0036] On the other hand, Control 1 showed significant movement of salicylic acid. However, Control 1 has a significantly lower pH and a larger cationic charge than Examples 1, 2, and 3 and Control 2. Generally, a low pH and a large cationic charge improve the penetration of the active substance into the skin. However, a low pH is not suitable for topical skin products. In this way, Examples 1, 2, and 3 according to the present invention provide an alternative means for significant delivery of the active substance. Furthermore, compared over 24 hours, there is little salicylic acid released from Control 1. This is in contrast to Examples 1, 2, and 3, which show controlled release meaning slow release over time, as Control 1 undergoes free release. Based on the standard deviation of the amounts of movement reported in Table 3, Example 2 yielded better results (further controlled release) than Examples 1 and 3.

[0037] Although specific embodiments of the present invention have been described, it will be apparent to those skilled in the art that other modifications are possible without departing from the spirit and scope of the present invention. Accordingly, all modifications within the scope of the present invention are intended to be included in the appended claims.

Claims

1. A topical aqueous composition for the controlled release of an active ingredient, a film-forming agent containing an acrylate / VA copolymer and an acrylate copolymer in a weight ratio of 10:1 to 30:1, wherein the combined weight of the acrylate / VA copolymer and the acrylate copolymer is 20% to 60% of the total weight of the composition, a porosity regulator containing 1,3-propanediol and glycerin in a weight ratio of 1:1 to 4:1, wherein the combined weight of 1,3-propanediol and glycerin is 5.5% to 10% of the total weight of the composition, one or more cosmetically acceptable active ingredients in a total concentration of 0.0001% to 10% by weight of the composition and containing a topical aqueous composition.

2. The topical aqueous composition according to claim 1, wherein the active ingredient is salicylic acid.

3. The topical aqueous composition according to claim 1, wherein the active ingredient is hyaluronic acid.

4. The topical aqueous composition according to claim 1, wherein the active ingredient is glycolic acid.

5. The topical aqueous composition according to claim 1, wherein the weight ratio of the acrylate / VA copolymer to the acrylate copolymer is in the range of 15:1 to 25:

1.

6. The topical aqueous composition according to claim 1, wherein the weight ratio of 1,3-propanediol to glycerin is in the range of 1:1 to 3:

1.

7. The topical aqueous composition according to claim 1, containing 1,3-propanediol and glycerin together in an amount of 5.5% to 7% of the total weight of the composition.

8. The topical aqueous composition according to claim 1, wherein when the composition is applied to a substrate and dried, the active ingredient accumulates in the pores formed in the film.

9. The topical aqueous composition according to claim 8, wherein the average pore size ranges from about 0.1 μm to about 1.5 μm. **Claim 10** The topical aqueous composition according to claim 8, wherein the average pore size ranges from about 1.5 μm to about 3.0 μm.

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