Compositions for controlled release of active substances

Abstract

A topical film-forming composition capable of efficiently delivering an active ingredient to a keratin surface in a timed release manner comprises a combination of an acrylate copolymer and an acrylate / VA copolymer and a combination of propan-1, 3-diol and glycerol. The aperture of pores formed in the dry film can be controlled or finely tuned.

Description

Field of the Invention

[0001] The present invention is in the field of topical formulations for keratinous surfaces. More specifically, the present invention relates to film-forming compositions capable of effectively delivering active ingredients to the skin in a controlled release manner. Background of the Invention

[0003] In the following commonly owned applications, US15 / 632903 (now US Pat. No. 11103439), US15 / 906372 (now US Pat. No. 10813874), US17 / 029147, US17 / 176527, US16 / 816995, US16 / 197858, US16 / 381806 (now US Pat. No. 10507175), US16 / 267441 (now US Pat. No. 10980717), US17 / 189768 and US16 / 827876 (now US Pat. No. 11129788), all of which are incorporated herein by reference in their entirety, applicants disclose specific combinations of acrylate / VA copolymers and acrylate copolymers in an aqueous matrix, and various useful properties of these combinations depending on the application and the presence of certain other ingredients. Although water-based, these compositions dry to a clear, flexible, and comfortable film when applied to the skin surface.

[0004] In US 16 / 267441 (now US Pat. No. 10,980,717), we disclosed low ethanol perfume compositions comprising (by total composition weight) about 50-60% water, 3-30% aromatic ingredients, 4.5-18.5% acrylate / VA copolymer, 0.25-1.0% acrylate copolymer (wherein the weight ratio of acrylate / VA copolymer to acrylate copolymer is in the range of 10:1 to 30:1), one or more plasticizers, which may be up to 4.5% glycol (butylene glycol, propylene glycol, 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 is worth noting that, in general, more plasticizer in the aqueous phase tends to increase the size of the surface pores formed in the film when the acrylate / VA copolymer-acrylate copolymer combination dries. Controlling this pore size is key to controlling the release of fragrance over time. In contrast to the present invention, we note that the diffusion of fragrance molecules from the aromatic ingredients located in the pores of the dry film into the air is different from the release of active ingredients from the pores of the dry film into the skin, which is driven by osmotic pressure.

[0005] In US 16 / 827876 (now US Pat. No. 11,129,788), we disclose spray film-forming compositions comprising (by total composition weight) about 70-85% water, 4.7-14% acrylate / VA copolymer, 0.05-2.5% acrylate copolymer, 1-5% plasticizer (which may be any of glycerol, propylene glycol, butylene glycol, or a combination thereof). The weight ratio of acrylate / VA copolymer to acrylate copolymer is reported to be 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. The plasticizer is reported to have an effect on the porosity of the dried film. It is also reported that when these compositions are applied to a substrate and allowed to dry, the average porosity of the dried film is 0.25 μm to 3.0 μm. It is also stated that the pore size makes the compositions disclosed therein useful as delivery vehicles for active ingredients. In particular, pore sizes of 0.9 μm to 2.5 μm are particularly useful for controlled or sustained release of active ingredients. Examples of active ingredients that can be incorporated into the water phase or the oil phase are disclosed.

[0006] None of the above references discloses a more robust delivery system for the controlled release of active substances.

[0007] Purpose of the Invention

[0008] The main object of the present invention is to provide a robust delivery system for the controlled release of active substances which remains comfortable on the skin for a long time, resists contact transfer, but is easily removed by rubbing under water. Summary of the invention

[0009] The topical composition for controlled release of active ingredients comprises 20% to 60% by weight of a combination of acrylate copolymers and acrylate / VA copolymers, wherein the weight ratio of acrylate / VA copolymer to acrylate copolymer is 10:1 to 30:1, preferably 15:1 to 25:1, more preferably about 20:1. The composition also comprises 5.5%-10%, preferably 6%-7%, of a combination of propane-1,3 glycol and glycerol, wherein the weight ratio of propane-1,3 glycol to glycerol is from about 1:1 to about 4:1, preferably from about 2:1 to about 3:1. When these compositions are applied to a substrate (e.g., a keratin surface) and allowed to dry, the average porosity of the dried film is from about 0.1 μm to 10 μm.

[0010] Detailed Description

[0011] Except for the operating examples and comparative examples, or otherwise explicitly stated, all numbers in this specification indicating material amounts or ratios or reaction conditions, material physical properties and / or uses should be understood to be modified by the word "about". Unless otherwise stated, all amounts are expressed in weight percentages of the final composition.

[0012] Throughout this specification, "film former" and the like refer to a polymer that leaves a film on a substrate to which it is applied, for example, after a solvent accompanying the film former evaporates, is absorbed into the substrate, and / or dissipates on the substrate.

[0013] "Comprising" means that the list of elements may not be limited to the elements explicitly listed.

[0014] Acrylate / VA copolymer

[0015] The first major component of the present invention is acrylates / 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 more information, see PubChem compound database; CID = 168269.

[0016]

[0017] In cosmetics, this viscous material is often used as a binder, film former, adhesive and / or hair fixative. When acrylate / VA copolymers are used in aqueous cosmetic systems, they can form a film on the skin or hair. Pure acrylate / VA copolymer films have temperature-dependent characteristics, so that washing with water at about 38°C or higher degrades the film and removes it from the surface, while maintaining its integrity at normal skin temperature or below normal skin temperature (i.e., 36.5-37.5°C).

[0018] Acrylate / VA copolymers are commercially available, for example, as Vinysol 2140L from Daido Chemical Corp. Vinysol 2140L is a 46.6% aqueous mixture of acrylate / VA copolymers. Vinysol 2140L is reported to have a pH of 4.5, a viscosity of 2,000 mPa-s, a calculated glass transition temperature (Tg) of -9°C, and a film elongation at break of 1,200% and a breaking strength of 1.2 MPa (when spread at a thickness of 0.1 mm). Acrylate / VA copolymers themselves are a bit too stiff for consumer acceptance.

[0019] Acrylate copolymer

[0020] In order to solve the problem of high rigidity, acrylate / VA copolymer and acrylate copolymer C 14 H 22 O6 combination, the latter also known as ethyl 2-propeneate; methyl 2-methylpropene-2-enoate or 2-methylpropene-2-enoic acid (IUPAC name); CAS number 25133-97-5. This acrylate copolymer has a lower Tg than the acrylate / VA copolymer. For more information, see PubChem Compound Database; CID=168299. Acrylate copolymers have a wide range of uses in various types of cosmetic formulations, including as film formers, hair fixatives, binders and suspending agents, viscosity enhancers, antistatic agents, and adhesives.

[0021] Acrylate copolymers are commercially available, for example as Daitosol 5000AD from Daito Kasei Kogyo Co. Daitosol 5000AD is a 50% aqueous mixture of acrylate copolymers. 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 (Tg) of about -14°C.

[0022] The topical aqueous composition of the present invention comprises a film former comprising an acrylate / VA copolymer and an acrylate copolymer in a weight ratio of 10:1 to 30:1, wherein the total weight of the acrylate / VA copolymer and the acrylate copolymer accounts for 20%-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, such as 19:1 to 21:1. For example, one useful composition embodiment comprises 40% acrylate / VA copolymer and 2% acrylate copolymer.

[0023] Porosity Regulator

[0024] As mentioned above, the composition according to the present invention is water-based, but dries into a porous film after application to the skin. As the film dries, the molecules of the one or more active ingredients accumulate in the pores of the dried film, which prevents the one or more active ingredients from aggregating in large quantities. This ensures that the particle size of the one or more active ingredients remains small enough to penetrate the skin. Subsequently, under the action of osmotic pressure, these active molecules are released from the pores of the film into the skin.

[0025] However, in general, the porosity needs to be further adjusted so that the incorporated molecules are not released too slowly or too quickly. If the release is too slow, the active ingredient may not produce the desired effect in the skin. If the release is too fast, the active ingredient is more likely to irritate the skin. We have discovered how to control the release of active materials from the above-mentioned films by adjusting the porosity of the film, and do so without destroying many of the useful properties of the film, especially its breathability. By breathability, we mean the breathability of the dry film. Generally, after drying, it has been observed that the compositions of the present invention allow air to pass through even at ambient pressures as low as 1 psi. Maintaining the breathability of the dry film is important for the comfort of the user.

[0026] The porosity (or pore size) is controlled by adding a porosity regulator to the composition. The porosity regulator comprises propane-1,3 glycol and glycerol in a weight ratio of about 1:1 to 4:1, wherein the total weight of propane-1,3 glycol and glycerol accounts for about 5.5% to 10% of the total composition weight. Preferably, the weight ratio of propane-1,3 glycol to glycerol is about 1:1 to 3:1, more preferably 2:1 to 2.5:1. Preferably, the total weight of propane-1,3 glycol and glycerol is about 5.5% to about 7% of the total weight of the composition, more preferably about 6%. For example, a combination of 4% propane-1,3 glycol and 2% glycerol yields a total of 6% porosity regulator that meets this requirement.

[0027] As described above, we have observed that the pore size in the dry film can be controlled or fine-tuned by the combination of propane-1,3 glycol and glycerol as defined above. In general, the greater (less) the amount of porosity regulator, the larger (smaller) the pore size of the film on average. Using the concentrations disclosed above, it is possible to produce a membrane having an average pore size of about 0.1 μm to 10 μm, wherein the range of the pore size average can be fine-tuned. For example, a polymer membrane can be produced in which 75%-90% of the pore size is within about 1 μm, while the other 10%-25% of the pore size will be above or below this range. For example, we have produced a polymer membrane according to the present invention in which about 80% of the pore size is 1.75-2.75 μm, about 10% of the pore size is 1.00-1.75 μm, and about 10% of the pore size is 2.75-3.75 μm. Larger pores may release active ingredients faster than ideal, but the amount of active ingredient released is relatively small and is less likely to cause irritation. Since all or most of the actives are trapped in similar sized pores (within about 1 μm), the release of most of the actives is controllable. If the pore size distribution is too broad, controlled release suitable for the topical personal care market is unlikely to be achieved. In the compositions of the present invention, 75%-90% of the pore sizes in the dry polymer film are preferably within about 2 μm, more preferably within 1.5 μm, and most preferably within 1.0 μm.

[0028] Active ingredients

[0029] The active ingredients may be incorporated into the aqueous phase or the oil phase (if any). Non-limiting examples of hydrophilic (water-soluble) actives include: algae extract, Alpinia galanga leaf extract, Alteromonas fermentation product extract, ascorbyl glucoside (AA2G), watermelon fruit extract, hawthorn flower extract, hyaluronic acid, hydrolyzed yeast protein, lactic acid bacteria ferment, Matricaria (chamomile) extract, lentil fruit extract, peony root extract, panthenol, apple fruit extract, and sugar cane extract. Non-limiting examples of hydrophobic (oil-soluble) actives include chamomile oil, bht (butylated hydroxytoluene), caffeine, coconut oil, salicylic acid, vitamin A, tetrahexyldecyl ascorbate, and tocopheryl acetate. The total concentration of all active ingredients is typically 0.0001% to about 10% by weight of the composition.

[0030] water

[0031] The compositions of the present invention are aqueous and typically contain at least about 25% water by weight of the total composition. Preferably, the total amount of water is at least 50%. This amount of water comes from all sources, such as the water in Vinysol 2140L and Daitosol 5000AD.

[0032] Optional Ingredients

[0033] The compositions of the present invention may also contain preservatives as desired, typically up to about 2% by weight of the composition. In addition, viscosity modifiers and / or pH modifiers may be used as desired to produce a consumer acceptable product, typically at levels less than 1% by weight of the composition. At these levels, preservatives, viscosity modifiers, and pH modifiers do not appear to adversely affect the controlled release of active substances from the dried polymer film.

[0034] Some preferred embodiments of the present invention are single-phase aqueous compositions in which there is little or no oil or silicone. However, in other preferred embodiments, the composition is a lightly emulsified oil-in-water emulsion. The emulsion embodiment is 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 embodiment may contain one or more surfactants or emulsifiers with an HLB of 8 to 12, and account for no more than 2% of the total composition, typically 0.01% to 2% of the total composition.

[0035] Agents that significantly interfere with the dry film structure may have a negative impact on the controlled release of the active substance from the dry polymer film. Therefore, it is preferred that the composition of the present invention comprises not more than 0.5% of a structurant in total, for example 0.0001% to 0.5% of a structurant, for example Wax, clay (e.g. bentonite) or stearic acid. More preferably, the composition of the present invention comprises no more than 0.001% structurant in total. Most preferably, the composition of the present invention does not comprise a structurant. A useful exception to this rule is sodium stearate. Unlike many structurants, sodium stearate is partially hydrophilic, which makes it suitable for use in aqueous systems. Although sodium stearate is partially hydrophobic, its use does not appear to compromise the purposes of the present invention. This makes it particularly useful in embodiments of the present invention when a structurant may be needed. Sodium stearate can be used as a structurant, accounting for 0.0001% to 4% of the total composition weight. Exceeding this amount will begin to undermine the strength of the acrylic bond, which may have a negative impact on the controlled release of the active substance from the dry polymer film.

[0036] We have noticed that polyurethane tends to make the composition of the present invention very hard and has a negative impact on the controlled release of the active substance from the dried polymer film. Therefore, the film-forming composition of the present invention comprises no more than 0.5% polyurethane, for example 0.0001% to 0.5%. More preferably, the composition of the present invention does not comprise polyurethane.

[0037] Active substance delivery

[0038] When the composition of the present invention is applied to a substrate and allowed to dry, the dried film contains pores in which the molecules of the active ingredient accumulate. Thereafter, osmotic pressure drives the active molecules out of the pores of the film and into the skin.

[0039] In practice, the porosity of the dry film will be selected based on the molecular weight of the active material and the desired release rate. In general, the larger the molecular weight of the active ingredient, the larger the pore size required to allow the molecules of the active ingredient to accumulate in the pores of the film. The release rate will be selected based on the tendency of the active substance to irritate the skin and the expected benefit. A slower release rate (smaller porosity) may be required to avoid unacceptable levels of irritation, but a release rate that is too low may not provide significant benefits. Through routine trial and error, a membrane with a specific pore size distribution and release rate can be obtained for each specific active substance.

[0040] For example, in useful compositions of the present invention, the active ingredient is glycolic acid (hydrophilic; molecular weight 76.05 g / mol), and the average pore size is about 1.5 μm. In other compositions of the present invention, the active ingredient is salicylic acid (hydrophobic; molecular weight 138 g / mol), and the useful average pore size is about 1.6 μm to about 3.0 μm. More generally, for molecular weights ranging from about 30 to about 90 g / mol, the useful average pore size range can be from about 0.1 μm to about 1.5 μm. For molecular weights ranging from 90-300 g / mol, the useful average pore size range can be from about 1.5 μm to about 3.0 μm. When the pore size of the dry film is adjusted according to the molecular weight of the active molecule, the topical composition of the present invention exhibits controlled release of the active ingredient, thereby significantly reducing or eliminating inflammation or irritation of the skin. The following example demonstrates the controlled release of salicylic acid in a composition of the present invention containing 1% salicylic acid.

[0041]

[0042] Vinysol 2140L - a 46.6% aqueous mixture of acrylate / VA copolymer.

[0043] Daitosol 5000AD - a 50% aqueous mixture of acrylate copolymers.

[0044] UCON TM Fluid - 99.95% PPG-14 butyl ether / 0.05% BHT (as a solubilizer for salicylic acid).

[0045]

[0046]

[0047] Control 2 and blank skin provided a baseline for fluorescence measurements. As shown in Table 3, the migration of salicylic acid in Control 2 was minimal. Control 2 did not contain a porosity modifier (i.e., a combination of propane-1,3 glycol and glycerol), which is an ineffective active ingredient delivery system.

[0048] In contrast, Control 1 exhibited significant salicylic acid migration. However, Control 1 had a significantly lower pH than Examples 1, 2 and 3 and Control 2, and a greater cationic charge. In general, lower pH values ​​and greater cationic charge increase the penetration of active substances into the skin. However, low pH values ​​are not suitable for topical skin products. Therefore, Examples 1, 2 and 3 according to the present invention provide an alternative method for significant active substance delivery. In addition, after 24 hours, Control 1 released relatively less salicylic acid. This is because Control 1 experienced free release, while Examples 1, 2 and 3 exhibited controlled release, i.e., gradual release over time. Based on the standard deviation of the migration amounts reported in Table 3, Example 2 obtained better results (more controlled release) than Examples 1 and 3.

[0049] Although specific embodiments of the present invention have been described, it will be apparent to those skilled in the art that various other modifications may be made without departing from the spirit and scope of the present invention. Therefore, all modifications within the scope of the present invention are intended to be encompassed by the appended claims.

Claims

1. A topical aqueous composition for controlled release of an active ingredient comprising: a film former comprising an acrylate / VA copolymer and an acrylate copolymer in a weight ratio of 10:1 to 30:1, wherein the total weight of the acrylate / VA copolymer and the acrylate copolymer accounts for 20% to 60% of the total weight of the composition; A porosity regulator comprising propane-1,3 glycol and glycerol in a weight ratio of 1:1 to 4:1, wherein the total weight of propane-1,3 glycol and glycerol accounts for 5.5% to 10% of the total weight of the composition; and One or more cosmetically acceptable active ingredients are present in a total concentration of 0.0001% to 10% by weight of the composition.

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

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

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

5. The topical aqueous composition of claim 1, wherein the weight ratio of acrylates / VA copolymer to acrylates copolymer is from 15:1 to 25:

1.

6. The topical aqueous composition of claim 1, wherein the weight ratio of propane-1,3 glycol to glycerol is from 1:1 to 3:

1.

7. The topical aqueous composition of claim 1, wherein the combination of propane-1,3 glycol and glycerin comprises 5.5% to 7% by weight of the total composition.

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

9. The topical aqueous composition of claim 8, wherein the average pore size is from about 0.1 μm to about 1.5 μm.

10. The topical aqueous composition of claim 8, wherein the average pore size is from about 1.5 μm to about 3.0 μm.

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