WO2017179041A1

WO2017179041A1 - Microcapsules encapsulating silicone materials

Info

Publication number: WO2017179041A1
Application number: PCT/IL2017/050427
Authority: WO
Inventors: Danny Goldstein; Shaher Duchi; Hagay LADANY; Mali GEDASI
Original assignee: Tagra Biotechnologies Ltd
Current assignee: Tagra Biotechnologies Ltd
Priority date: 2016-04-11
Filing date: 2017-04-06
Publication date: 2017-10-19
Anticipated expiration: 2018-10-11

Abstract

Microcapsules encapsulating a silicone material in an outer layer (shell) made of a wall-forming polymeric material, which release the silicone material upon application to the skin, are disclosed. Processes for preparing the microcapsules, and formulations and products containing same are also disclosed.

Description

MICROCAPSULES ENCAPSULATING SILICONE MATERIALS

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to encapsulation and, more particularly, but not exclusively, to microcapsules encapsulating silicone materials, to processes of preparing such microcapsules and to products comprising such microcapsules.

Silicones, or silicone materials, are a class of compounds made up of repeating units of siloxane, a chain of alternating silicon atoms and oxygen atoms, optionally in combination with carbon and/or hydrogen containing groups. Some common forms include silicone oil, silicone grease, silicone rubber (elastomeric silicone), silicone resin, and silicone caulk.

Silicones are also known as polysiloxanes, and typically feature a silicon-oxygen backbone chain (•••-Si-O-Si-O-Si-Ο-···) with organic side groups attached to the silicon atoms. Silicones can be considered as comprised of a plurality of backbone units of the general formula [R₂SiO]„, where R is an organic group such as alkyl, alkenyl, alkoxy, cycloalkyl, aryl, and the like, or an organic polymer such as, for example, a polyether, or optionally hydrogen. Terminal groups may also vary.

Depending on the structure of the backbone chain, and/or the side (pendant) groups and/or terminal groups, the final structure of silicones can be determined. The backbone chain can be linear or branched, and side (pendant) groups may cross-link to form three-dimensional structures.

The length and structure of the backbone chain, the nature of the side and/or terminal chains and the presence or absence of crosslinking determines the properties of the silicone. Thus, for example, silicones can feature variable consistency, ranging from liquid to gel to rubber to hard plastic.

The most commonly used polysiloxane is a linear polydimethylsiloxane (PDMS; Dimethicone), a silicone oil. The second largest group of silicone materials is based on silicone resins, which are formed by branched and cage-like oligosiloxanes, and include, for example, elastomeric silicone.

Silicones are ingredients in many hair conditioners, shampoos, and hair gel products. Some silicones, typically amine-functionalized dimethicones, are excellent conditioners, providing improved compatibility, feel, and softness, and lessening frizz. Phenyltrimethicones are used in reflection-enhancing and color-correcting hair products, where they increase shine and glossiness (and possibly effect subtle color changes). Phenyltrimethicones, unlike the conditioning dimethicones, have refractive indices (typically 1.46) close to that of human hair (1.54). However, if included in the same formulation, dimethicone and phenyltrimethicone interact and dilute each other, making it difficult to achieve both high shine and excellent conditioning in the same product.

Silicones are also used in shaving products and personal lubricants.

When used in skin care products, silicones often impart emollience, silk-like feel, and smooth, creamy, rich appearance of the products, as well as other benefits like nourishing properties to the treated skin. Silicones are also extensively used for wound healing and for improving the appearance of scars.

However, the inclusion of silicone materials in skin care, hair care, and other topical formulations, is often limited. For example, as most silicone materials are hydrophobic, their inclusion in aqueous formulations requires the use of surfactants and/or of a limited amount of the silicone material. Silicone materials such as, for example, silicone elastomers, often act as rheology modifiers, typically by absorbing the formulation's carrier, leading to undesirable thickening of the composition. Silicone materials may further pose compatibility limitations, when formulated along with other ingredients. Commonly used silicone-containing preparations include up to 15 % by weight of the silicone material.

International PCT Patent Application Publication No. 2015/166448 describes a composition for caring for and/or making up keratin materials, comprising a physiologically acceptable medium and microcapsule containing silicone elastomer(s).

U.S. Patent No. 6,932,984, by the present assignee, discloses single- and double- layer microcapsules and a method for microencapsulation of substances by the solvent removal method using non-chlorinated solvents. The method is based on physical processes which do not cause any change of original physical and/or chemical properties, biological activity, and safety of raw materials during the process.

U.S. Patent No. 7,838,037, by the present assignee, discloses double-layer and/or triple-layer microcapsules, designed to rupture by a slight mechanical action such as rubbing or pressing on the skin, and thereby immediately release their encapsulated content. These microcapsules are prepared by the solvent removal method using non-chlorinated solvents. This method affords physical stability to the microcapsules, high ability to entrap the active agents, protection of the active agents inside the microcapsules, and prevention of the diffusion of the microencapsulated active agents to the external water phase in a water-based preparation.

WO 2009/138978, by the present assignee, discloses cosmetic compositions for dermal/topical application comprising double-layer, rupturable microcapsules which contain one or more microencapsulated colorants. When applied to the skin, such compositions produce an immediate color change effect indicating the delivery to the skin of the active substances contained in said compositions.

SUMMARY OF THE INVENTION

A need exists for novel methodologies that enable the inclusion of silicone materials in topical formulations while maintaining the rheological properties of the formulation, while circumventing the need for surfactants in aqueous formulations, while allowing inclusion of agents that are otherwise incompatible with silicone materials, and/or which include silicone materials in an amount higher than currently practiced.

The present inventors have now designed and successfully practiced a methodology for encapsulating silicone materials in microcapsules which release the silicone material once applied to the skin.

According to an aspect of some embodiments of the present invention there is provided a microcapsule comprising an inner core enveloped by an outer shell formed of a wall-forming polymeric material, the inner core comprising a silicone material.

According to some of any of the embodiments described herein, an amount of the inner core is at least 50 weight percents of the total weight of the microcapsule.

According to some of any of the embodiments described herein, an amount of the silicone material ranges from about 50 % to about 90 %, by weight, of the total weight of the microcapsule. According to some of any of the embodiments described herein, an amount of the silicone material ranges from about 70 % to about 90 %, or from about 80 % to about 90 %, by weight, of the total weight of the microcapsule.

According to some of any of the embodiments described herein, the inner core consists of the silicone material.

According to some of any of the embodiments described herein, the silicone material is selected from the group consisting of a silicone oil (e.g., a dimethicone, a phenyltrimethicone), and a silicone resin (e.g., a silicone elastomer) and any combination thereof.

According to some of any of the embodiments described herein, the silicone material comprises a dimethicone.

According to some of any of the embodiments described herein, the dimethicone features a viscosity of from 50 to 5000 centipoises at room temperature.

According to some of any of the embodiments described herein, the microcapsule further comprises a fatty substance (e.g., in the outer shell).

According to some of any of the embodiments described herein, the fatty substance is a fatty acid salt.

According to some of any of the embodiments described herein, the fatty acid is selected from the group consisting of stearic acid, arachidic acid, palmitoleic acid, oleic acid, linoleic acid, linolaidic acid, arachidonic acid, myristoleic acid and erucic acid.

According to some of any of the embodiments described herein, the fatty acid salt is selected from the group consisting of magnesium stearate, magnesium oleate, calcium stearate, calcium linoleate, and sodium stearate.

According to some of any of the embodiments described herein, the fatty substance is a glycolipid.

According to some of any of the embodiments described herein, the fatty substance is a propylene glycol stearate.

According to some of any of the embodiments described herein, the fatty substance further comprises a fatty acid.

According to some of any of the embodiments described herein, an amount of the fatty acid salt ranges from about 0.1 % to about 10 %, or from about 1 % to about 10 %, by weight, of the total weight of the microcapsule. According to some of any of the embodiments described herein, the wall- forming polymeric material comprises a polymer or copolymer selected from the group consisting of polyacrylate, a polymethacrylate, a cellulose ether, a cellulose ester, copolymers thereof and any combination thereof.

According to some of any of the embodiments described herein, the polymer or copolymer is selected from the group consisting of a polyacrylate, a polymethacrylate, an acrylate/ammonium methacrylate copolymer, an ammonium methacrylate copolymer type B, low molecular weight (about 15,000 Dalton) poly(methyl methacrylate)-co-(methacrylic acid), poly(ethyl acrylate)-co-(methyl methacrylate) - co-(trimethyl ammonium-ethyl methacrylate chloride), poly(butyl methacrylate)-co-(2- dimethy laminoethyl methacrylate )-co-(methyl methacrylate)), poly(styreneJ-co- (maleic anhydride), copolymer of octylacrylamide, cellulose ether, cellulose ester, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), PLA (poly lactic acid), PGA (poly glycolic acid) and PLGA copolymer.

According to some of any of the embodiments described herein, the wall- forming material comprises a cellulose ester.

According to some of any of the embodiments described herein, the wall- forming material comprises cellulose acetate propionate.

According to some of any of the embodiments described herein, an amount of the wall-forming polymeric material ranges from about 1 % to about 50 %, or from about 5 % to about 20 %, or from about 10 % to about 15 %, by weight, of the total weight of the microcapsule.

According to some of any of the embodiments described herein, the microcapsule further comprises a colorant and/or an opaque substance.

According to some of any of the embodiments described herein, the colorant is in the inner core.

According to some of any of the embodiments described herein, the colorant and/or the opaque substance are in the outer shell.

According to some of any of the embodiments described herein, the microcapsule further comprises an additional active agent.

According to some of any of the embodiments described herein, the additional active agent is in the inner core. According to some of any of the embodiments described herein, the microcapsule further comprises a plasticizer.

According to some of any of the embodiments described herein, the plasticizer is selected from the group consisting of triethyl citrate, tricaprylin, trilaurin, tripalmitin, triacetin, acetyltriethyl citrate, paraffin oil, and any combination thereof.

According to some of any of the embodiments described herein, the outer shell comprises:

the wall-forming polymeric material in an amount that ranges from about 5 % to about 20 %, by weight, of the total weight of the microcapsule; and

the fatty acid salt in an amount that ranges from about 0 to about 10 %, by weight, of the total weight of the microcapsule.

According to some of any of the embodiments described herein, the wall- forming polymeric material comprises a cellulose acetate; the fatty acid salt is a salt of stearic acid; and the inner core comprises dimethicone.

According to some of any of the embodiments described herein, the microcapsule is a single-layer microcapsule.

According to an aspect of some embodiments of the present invention there is provided a composition comprising a plurality of microcapsules, at least a portion of the microcapsules comprising the microcapsules as described herein in any of the respective embodiments and any combination thereof.

According to some of any of the embodiments described herein, at least 50 %, or at least 80 %, or at least 90 % of the microcapsules are the microcapsules described herein.

According to some of any of the embodiments described herein, substantially all of the microcapsules are microcapsules as described herein.

According to some of any of the embodiments described herein, a mean size of the plurality of microcapsules ranges from about 1 μιη to about 1000 μιη, or from about 50 μιη to about 500 μιη, or from about 50 μιη to about 200 μιη, or from about 50 μιη to about 150 μιη, or is about 100 μιη.

According to some of any of the embodiments described herein, the composition is in a form of a powder or a paste. According to an aspect of some embodiments of the present invention there is provided a process of preparing the microcapsule or the composition as described herein, the process comprising:

(a) contacting an organic phase comprising the silicone material, a wall- forming polymer or copolymer, optionally a fatty acid salt (if present), and a partially water-miscible organic solvent, with an aqueous continuous phase saturated with the organic solvent and comprising an emulsifier, to thereby obtain an emulsion; and

(b) contacting the emulsion with an extraction medium which comprises an amount of water which initiates extraction of the organic solvent from the emulsion, thereby obtaining the plurality of microcapsules.

According to some of any of the embodiments described herein, the process further comprises isolating the microcapsules.

According to some of any of the embodiments described herein, the process further comprises drying the microcapsules.

According to some of any of the embodiments described herein, the organic solvent is selected from ethyl acetate, methyl acetate, ethanol, ethyl formate, and any combination (mixture) thereof.

According to an aspect of some embodiments of the present invention there is provided a microcapsule or a composition comprising a plurality of microcapsules, prepared by the process as described herein in any of the respective embodiments.

According to some of any of the embodiments described herein, a microcapsule as described herein is rupturable upon application of shear and/or mechanical force, thereby releasing the silicone material.

According to an aspect of some embodiments of the present invention there is provided a formulation comprising the microcapsule or the composition as described herein in any of the respective embodiments and any combination thereof.

According to some of any of the embodiments described herein, the formulation is for topical application.

According to some of any of the embodiments described herein, the formulation further comprises a physiologically acceptable carrier.

According to some of any of the embodiments described herein, the formulation is formulated as an oil-in-water emulsion, oil-in-water-in-oil emulsion, water-in-oil emulsion, a water-in-oil-in-water emulsion, an aqueous formulation, an anhydrous formulation, a silicon-based formulation and a powder formulation.

According to some of any of the embodiments described herein, the formulation is an aqueous-containing formulation, that is, the formulation is an aqueous formulation or comprises an aqueous solution (e.g., is a water-based formulation).

According to some of any of the embodiments described herein, the formulation is devoid of a surfactant.

According to some of any of the embodiments described herein, the formulation is in the form of a gel, a powder, cream, foam, a stick, lotion, ointment, spray, oil, paste, milk, suspension, aerosol, or mousse.

According to an aspect of some embodiments of the present invention there is provided an article-of-manufacturing comprising the microcapsule or the composition or the formulation, as described herein in any of the respective embodiments and combination thereof.

Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways. The present inventors have designed and successfully practiced a novel methodology for efficiently encapsulating, in core-shell microcapsules, silicone materials. The present inventors have shown that using this novel methodology, encapsulation of a silicone material such as dimethicone in high load (e.g., higher than 70 %, of the total weight of the microcapsule) is enabled.

The microcapsules obtained by this methodology, while encapsulating the silicone material in high load, can be provided as a free-flowing powder, or as a slurry, are highly stable during manufacturing and storage processes, are stable within cosmetic formulations, including aqueous formulations or water-containing emulsions, without affecting the rheological properties of the formulation, and while circumventing the need to include surfactants in such formulations, maintain the encapsulated agent inside the capsules with minimal or nullified leakage prior to use, and are rupturable under mild shear forces, thus enabling an immediate release of the encapsulated silicone material upon topical application of the microcapsules (e.g., to skin, hair, or any other keratinous tissue).

The provided microcapsules can be further loaded with other active ingredients, including pigments, colorants and/or pharmaceutically active agents (e.g., dermatologically active agents).

Some embodiments of the present invention relate to single-layer, core-shell microcapsules, encapsulating a silicone material, as described herein, which, on one hand, exhibit exceptional, unexpected, stability when compounded in industrial processes and when maintained in various formulations, including aqueous formulations and various emulsion-type formulations, and provide an adequate protection from "bleeding" effect within various cosmetic formulations and, on the other hand, are readily rupturable only by applying a mechanical pressure/shear force such as rubbing action of a formulation containing same onto skin, hair or any other keratinous tissue, thereby releasing the encapsulated agent. Multi-layer microcapsules encapsulating a silicone material, as described herein, are also contemplated.

The methodology utilized for preparing the microcapsules is based on physical processes which do not cause any change to the original physical and/or chemical properties and safety of raw materials during the process. This method affords physical stability of the microcapsules, ability to entrap the silicone material in high load, protection of the silicone material inside the microcapsules, and prevention of the diffusion of the encapsulated agent to the external medium in both oil-based, water- based, and emulsion-type preparations (before application).

Embodiments of the present invention therefore relate to a microcapsule comprising an inner core enveloped by an outer shell. The outer shell is formed of a wall-forming polymeric material, and the inner core comprises a silicone material.

Embodiments of the present invention further relate to a composition comprising a plurality of microcapsules, at least a portion of the microcapsules comprising an inner core enveloped by an outer shell, wherein the inner core comprises a silicone material, as described herein.

The silicone material:

The phrase "silicone material", which is also referred to herein simply as "silicone" encompasses organopolysiloxanes, as described herein and known in the art. This phrase encompasses silicone oils, silicone elastomers, and any organopolysiloxane- containing materials. The silicone materials can be in a form of a liquid, a gel or a solid material at room temperature. Any silicone materials known in the art are encompassed by the present embodiments.

In some embodiments, the silicone material is non-volatile.

Typically, volatile silicone materials are characterized by low molecule weight, for example, molecular weight of up to 400 grams/mol.

In some embodiments, the silicone material is characterized by a molecular weight of at least 450 grams/mol, or of at least 500 grams/mol, or of at least 600 grams/mol, or of at least 700 grams/mol, or of at least 800 grams/mol or of at least 1000 grams/mol.

In some of any of the embodiments described herein, the silicone material is a silicone oil, for example, organopolysiloxanes featuring a linear or cyclic silicone ((···- Si-O-Si-O-Si-Ο-···) backbone chain, which are liquid or pasty at room temperature, for example, silicone materials of the PDMS (dimethicone) family, including polysiloxanes bearing alkyl, alkoxy and/or phenyl groups as side (pendant) or terminal groups; cyclomethicones such as cyclohexasiloxane; phenyl silicones such as phenyl trimethicones, phenyl dimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes or 2-phenylethyl trimethylsiloxy silicates, and polymethylphenylsiloxanes; and any mixture thereof.

Non-limiting examples include dimethicone, cyclomethicone, polysilicone- 11, phenyl trimethicone, trimethylsilylamodimethicone, stearoxytrimethylsilane, and any mixture thereof.

In some embodiments, the silicone material comprises a dimethicone (PDMS) or a derivative thereof, which can be collectively represented by the following general formula:

Formula I wherein:

n and m are each independently 0 or a positive integer (provided that at least one of n and m is a positive integer ), wherein n + m is a positive integer representing the number of backbone units;

A and B are each independently a terminal group, which can be, for example, hydrogen, alkyl, alkoxy, hydroxy, alkenyl, vinyl, alkaryl, aryl, alkylene glycol, poly(alkylene glycol), heteroaryl, carboxy, thiocarboxy, a silane, a siloxane, and the like, or, alternatively, A and B are linked together to form a cyclic polysiloxane (cyclomethicone); and

Ri and R₂ are each independently a pendant group, which can be, for example, hydrogen, alkyl, alkoxy, hydroxy, alkenyl, vinyl, alkaryl, aryl, alkylene glycol, poly(alkylene glycol), heteroaryl, carboxy, thiocarboxy, and the like.

The sum of n + m, the ratio of n to m, and the nature of the pendant and terminal groups determine the properties of the silicone oil in terms of, for example, volatility, consistency, viscosity and the like.

In some embodiments, the silicone material is a silicone elastomer, which is also referred to herein as "polysiloxane elastomer" or "elastomeric silicone". The silicone elastomer can be included in the microcapsule as a solid material (e.g., particles) or as an aqueous dispersion containing the particles.

The silicone elastomer can be partially or totally cross-linked, and can have a three-dimension, cage-like structure.

Exemplary silicone elastomers usable in the context of the present embodiments are those described in U.S. Patent No. 5,928,660, which is incorporated by reference as if fully set forth herein.

Silicone elastomers can be prepared, for example, by polymerizing or cross- linking an organopolysiloxane containing at least two vinyl terminal or pendant groups, or co-polymerizing such a polysiloxane with a chemically-compatible polysiloxane (which can participate in a co-polymerization reaction, for example, by exhibiting a chemically compatible polymerizable group). An exemplary starting material is a dimethylvinylpolydimethylsiloxane.

The organopolysiloxane elastomer particles may have a size ranging from 0.1 to 500 μιη and better still from 3 to 200 μιη. These particles may be spherical, flat or amorphous, and are preferably of spherical form. These organosiloxane elastomer particles may be associated, in the aqueous suspension, with fatty substances, especially oils.

Exemplary aqueous suspensions of organopolysiloxane particles usable in the context of the present embodiments include, for example, those sold under the names BY 29-1 19, BY 29-122, BY 29-129 and DC 9509 by the company Dow Corning, the US INCI name of which is Dimethicone/vinyl dimethicone crosspolymer and C12-C14 pareth-12. These suspensions comprise about 63 % by weight of organopolysiloxane elastomer particles relative to the total weight of the composition.

Other exemplary suspensions include Gransil LTX sold by the company Grant

Industries, the INCI name of which is Cyclopentasiloxane (and) polysilicone- 11 (and) water (and) laureth-4 and in which the content of organopolysiloxane elastomer particles is between 14% and 20%; Gransil EP-9, also sold by the company Grant Industries, the INCI name of which is Polysilicone- 11 (and) water (and) laureth-12 (and) phenoxyethanol (and) ethylhexyl glycerine and in which the content of nonvolatile matter is between 59 % and 62%; and those sold under the name Gransil EP-LS sold by the company Grant Industries, which is Polysilicone-11 (and) laureth-12, and contains 99 % of Polysilicone- 1 1 elastomer and 1 % of laureth-12.

The aqueous suspensions may be used as such or after a drying step.

Other exemplary silicone elastomers include, but are not limited to, those sold under the names "DC 9040", "DC 9041", "DC 9509", "DC 9505" and "DC 9506" by the company Dow Corning; DC 9701, which is a spherical silicone elastomer powder coated with silica (I NCI name: dimethicone/vinyl dimethicone crosspolymer (and) silica) and DC EP 926 Iti, which is a silicone elastomer powder coated with titanium dioxide. Other silicone elastomers are also disclosed in U.S. Patent Application Publication No . 2005/0220728.

Other exemplary silicone elastomers include those sold under the names "KSP- 100", "KSP-101", "KSP-102", "KSP-103", "KSP-104" and "KSP-105" by the company Shin-Etsu. INCI name of "KSP-100", "KSP-101", "KSP-102", "KSP-105" is VINYL DMETHICONE/METHICONE SILSESQUIOXANE CROSSPOLYMER; hybrid silicone powders functionalized with fluoroalkyl groups, sold under the name "KSP- 200" by the company Shin-Etsu; hybrid silicone powders functionalized with phenyl groups, sold especially under the name "KSP-300" by the company Shin-Etsu. INCI name of "KSP-300" is DIPHENYL DMETHICONE/VINYL DIPHENYL DIMETHICONE/SILSESQUIOXANE CROSSPOLYMER; hybrid silicone powders "KSP- 441 " and "KSP-411" by the company Shin-Etsu, the INCI names of "KSP-441" and "KSP- 41 1 " being respectively Polysilicone-22 and Polysilicone- 1 Crosspolymer.

The microcapsules:

The microcapsules provided by the present embodiments are particles (e.g., generally spherical particles), which are generally closed structures containing an encapsulated (enveloped, entrapped) silicone material, optionally in combination with another ingredient, as described herein. The microcapsules generally have a core-shell structural feature, namely each microcapsule is comprised of a polymeric shell and a core that comprises the silicone material or may be consisted of the silicone material, enveloped by the shell.

The shell of the microcapsule is typically applied as a wall-forming material and serves as a membrane for the encapsulated substance. In some embodiments, the outer shell further comprises a fatty substance, as described herein. In some embodiments, the outer shell exhibits some opacity, by virtue of inclusion of an opaque substance in the shell, optionally in combination with a fatty acid salt.

The outer shell may further comprise a plasticizer to control its hardness, and/or a dispersing agent.

In some embodiments, the outer shell is designed such that the microcapsules are rupturable upon application of shear and/or mechanical forces, for example, by rubbing or pressing on the skin, hair or a keratinous tissue in general.

In some of any of the embodiments described herein, the microcapsules are single-layer microcapsules, comprising a single outer shell enveloping the inner core.

In some other embodiments, the microcapsules are double-layer, or triple-layer, or multi-layer microcapsules, comprising additional one or more layers enveloping the shell that envelopes the inner core.

A multi-layer microcapsule is featured as comprising an inner core microcapsule comprising a core which comprises one or more silicone materials, as described herein, being enveloped by a shell (e.g., a first shell) comprised of a wall-forming material (e.g., a first wall-forming material), and at least one additional shell comprised of a second wall forming material enveloping said first shell, which can be regarded as enveloping a single-layer microcapsule as described herein (comprising the silicone material-containing inner core and a first shell of a first wall-forming material).

Each shell in the multi-layered microcapsules is typically and independently applied as a wall-forming material (e.g., a first, second, third and so forth wall-forming materials forming the first, second, third, and so forth, outer shells, respectively), and serves as a membrane for the encapsulated substance. In some embodiments, one or more, or each, of the outer shells in the multi-layered microcapsules according to these embodiments is optionally opaque by virtue of an opaque substance comprised therein, and/or further contains a fatty acid salt, as described herein.

The microcapsules of the present embodiments, among other uses, are suitable for inclusion in topical, e.g., cosmetic, cosmeceutical and pharmaceutical (e.g., dermatological), applications. When applied to the skin, the microcapsules are capable of being ruptured upon application of shear forces such as rubbing and pressing on the skin, but they remain intact in the formulation itself before application, and exhibit exceptional stability in water-based, oil-based, silicon-based and emulsion-type formulations. The microcapsules are hard enough to avoid destruction of the shells and realization of the content during production processes such as isolation/filtration, drying, sieving, etc., and/or during storage.

The microcapsules according to the present embodiments are also referred to herein as silicone-encapsulating microcapsules or as microcapsules encapsulating a silicone material.

Herein throughout, the term "encapsulated" or "encapsulating" or any other grammatical diversions, means that the silicone material (and/or any other active agent as described herein) is always entrapped inside the microcapsules according to the invention.

In some embodiments, the outer layer of the microcapsules encapsulating the silicone material is free of (devoid of) the silicone material.

By "free of or "devoid of it is meant that the outer layer comprises less than 1 %, or less than 0.5 %, or less than 0.1 %, or less than 0.05 %, or less than 0.01 %, or less, by weight, of the total weight of the outer layer, and even null, of the silicone material as described herein in any of the respective embodiments.

In some embodiments, the microcapsules encapsulating the silicone material as described herein are prepared by a solvent removal method, as described hereinunder and exemplified in the Examples section that follows.

In some embodiments, a mean size of the microcapsules as described herein is within a range of from about 1 μιη to about 1000 μιη, or from about 10 μιη to about 1000 μιη, or from about 10 μιη to about 500 μιη, or from about 10 μιη to about 200 μιη, or from about 50 μιη to about 200 μιη, or from about 50 μιη to about 150 μιη, including any intermediate value or subranges therebetween. In some embodiments, a mean size of the microcapsules as described herein is 100 μιη.

In some of any of the embodiments described herein, the outer shell comprises, in addition to the wall-forming material, a fatty acid salt, as described herein.

According to some of any of the embodiments of the invention, a microcapsule as described herein is rupturable or breakable when applied to a keratinous tissue (e.g., skin or hair); that is, a microcapsule as described herein remains intact in a formulation containing same and during industrial processes, but readily breaks when pressed of rubbed on the keratinous tissue. The non-breakability of the microcapsules before topical application thereof is routinely assessed by monitoring (e.g., using a light microscope) the ability of the microcapsules in a basic formulation (e.g., cream or lotion) to sustain their size and shape when subjected to low shear mixing at e.g., 40- 600 (or 80-100) rpm for 5-10 minutes at room temperature and at 40 °C. A change of less than 10 % in the microcapsule size is indicative of the non-breakability of the microcapsules upon routine industrial processes.

The inner core:

The inner core in the microcapsules described herein comprises a silicone material as described herein.

In some embodiments, the inner core comprises one silicone material, for example, a silicone oil (e.g., a dimethicone), or a silicone elastomer.

In some embodiments, the inner core comprises a mixture of 2, 3 4 or more silicone materials.

In some embodiments, the silicone material comprises a mixture of a silicone oil and a silicone elastomer.

The silicone material can be in a form of a liquid, for example, a silicone oil as described herein, characterized by a viscosity, at room temperature, that ranges from 10 to 5000, or from 10 to 2000, or from 10 to 1500, or from to 1500, centipoises, including any intermediate values and subranges therebetween.

The silicone material can alternatively be in a form of particles, or of aqueous suspensions of particles, as described herein.

In some embodiments, the inner core constitutes at least 50 weight percents, or at least 60 weight percents, or at least 70 weight percents, of the total weight of the microcapsule.

In some embodiments, an amount of the silicone material ranges from about 50 % to about 90 %, by weight, of the total weight of the microcapsule.

In some embodiments, an amount of the silicone material ranges from about 70 % to about 90 %, or from about 80 % to about 90 %, by weight, of the total weight of the microcapsule. In some embodiments, the inner core comprises a blend of one or more silicone material(s) as described herein, and an additional ingredient (e.g., active agent), as described herein.

In some embodiments, whenever the inner core comprises two or more different silicone materials, the silicone materials are compatible with one another, that is, do not react with one another, and remain stable and maintain functionality when mixed with one another.

The wall-forming material:

The wall-forming material forms the outer shell(s) of the microcapsules of the present embodiments, and serves as a membrane for the encapsulated substance (the silicone material). According to embodiments of the present invention, the wall forming material forming the outer shell(s) comprises a wall-forming polymer or co-polymer. In some of any of the embodiments of the present invention, one or more of the outer shells further comprise a fatty acid salt, and may optionally further comprise a plasticizer and/or an opaque substance, or any of the other components described herein.

The phrase "wall-forming polymer", which is also referred to herein as "wall- forming polymeric material" refers to a polymeric material (e.g., a polymer or copolymer) or a combination of two or more different polymeric materials, as defined herein, which form a component of the external wall or layer or shell of single-layer microcapsules, or, in the case of multi-layer microcapsules, additionally of the one or more intermediate shells between the inner core and the external (outer most) layer. In the context of single-layer microcapsules, the term "polymer shell" refers to a polymer layer comprised of the wall-forming polymer(s), which envelopes the inner core. In the context of multi-layer microcapsules, the term "polymer shell" refers to any of the polymer layers which envelopes the inner core, or which envelopes the preceding polymer layer.

In some embodiments, the wall-forming polymer is selected so as to sustain shear forces applied while being compounded in industrial processes, but, nevertheless, so as to provide microcapsule which are rupturable when applied (e.g., rubbed or pressed) on a keratinous tissue. In some embodiments, the wall-forming polymeric material comprises a polymer containing a sufficient amount of functional groups which are capable of forming hydrogen bonds.

In some embodiments, the polymeric material forming the one or more outer shells independently comprises hydrogen bond-forming functional groups featuring 4- 40 weight percents of total polymer weight. Hydrogen bond-forming functional groups include, but are not limited to, functional groups which comprise one or more electron- donating atom(s) such as oxygen, sulfur and/or nitrogen.

In some embodiments, the hydrogen bond-forming groups include carboxylic acid, carboxylate, hydroxy, or any combination thereof.

In some embodiments, one or more, or each, of the wall-forming polymeric materials forming the outer shell(s) comprises a polyacrylate, a polymethacrylate, a cellulose ether or ester, or any combination thereof.

Exemplary wall-forming polymeric materials include, but are not limited to, polyacrylates, polymethacrylates, low molecular weight poly(methyl methacrylate)-co- (methacrylic acid) (e.g., 1:0.16), poly(ethyl acrylate)-co-(methyl methacrylate)-co- (trimethylammmonium-ethyl methacrylate chloride) (e.g., 1:2:0.1) (also known as Eudragit® RSPO), poly(butyl methacrylate)-co-(2-dimethylaminoethyl methacrylate)- co-(methyl methacrylate) (e.g., 1:2: 1), poly(styrene)-co-(maleic anhydride), copolymer of octylacrylamide, cellulose ethers, cellulose esters, poly(ethylene glycol) -block- poly(propylene glycol)-Woc£-poly(ethylene glycol), PLA (poly(lactic acid), PGA (poly(glycolide), PLGA (poly(lactide)-co-poly(glycolide) or any combination thereof.

Any combination of polymers and co-polymers as described herein is contemplated for a wall-forming material, as described herein.

In some embodiments, the wall-forming polymeric material of an outer shell comprises a cellulose ether or ester such as, but not limited to, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, cellulose acetate, cellulose acetate propionate (CAP), cellulose acetate phthalate, cellulose acetate butyrate and hydroxypropyl methyl cellulose acetate phthalate. When a cellulose ether or ester is used in the polymeric material, it preferably contains about 4-20 % hydroxyl groups which are free to form hydrogen bonds (e.g., hydroxyl groups which are not alkylated or acylated). In some of any of the embodiments described herein, the wall-forming material of an outer shell comprises an acrylate/ammonium methacrylate copolymer such as, for example, Eudragit® RSPO. In some of any of the other embodiments of the present invention, the wall-forming material of an outer shell comprises a combination of the above-mentioned polymers such as, but not limited to, a combination of two or more of a acrylate/ammonium methacrylate copolymer (e.g., Eudragit^® RSPO), poly(methyl methacrylate), poly (methacrylate), poly(methyl methacrylate)-co-(methacrylic acid) and a cellulose acetate.

When two polymeric materials are used as a wall-forming material, a weight ratio therebetween can range from 10: 1 to 1: 1, and can be, for example, 5: 1, 4: 1, 3: 1, 2: 1, 3:2, or 1: 1, including any intermediate values and subranges therebetween.

In some of any of the embodiments described herein, the wall forming material is or comprises poly(methyl methacrylate (PMMA).

In some of any of the embodiments described herein, the wall forming material is or comprises a poly(methyl methacrylate)-co-(methacrylic acid) (PMMA/MA).

In some of any of the embodiments described herein, the wall forming material is or comprises an acrylate/ammonium methacrylate copolymer (e.g., Eudragit^® RSPO).

In some of any of the embodiments described herein, the wall forming material is or comprises a cellulose acetate, for example, cellulose acetate propionate.

Other wall-forming materials usable in the context of the present embodiments include, but are not limited to, polyhydroxycarboxylic acids and its salts and esters thereof; poly aery lie acid/alkyl acrylate copolymers, preferably modified or unmodified carboxy vinyl polymers; AMPS; AMPS/acrylamide copolymers; polyoxyethylenated AMPS/alkyl methacrylate copolymers; anionic, cationic, amphoteric or nonionic chitin or chitosan polymers; cellulose polymers and derivatives; starch polymers and derivatives, eventually modified; vinyl polymers and derivatives; polymers of natural origins and derivatives thereof; alginates and carrageenans; glycoaminoglycans, hyaluronic acid and derivatives thereof; mucopolysaccharides such as hyaluronic acid and chondroitin sulfates; and the mixtures thereof.

The amount (weight/weight) of the wall-forming polymeric material(s) of the outer shell relative to the total microcapsule weight can be within a range of from about 5 % to about 30 %, or from about 5 % to about 20 %, or from about 5 % to about 15 %, or from about 10 % to about 15 %, by weight, including any subranges and any intermediate values therebetween.

In some embodiments, the wall-forming material is a cellulose ester such as cellulose acetate, and the outer shell may not comprise a fatty acid salt, as described herein.

In embodiments when the wall-forming material is cellulose acetate, the amount of the cellulose acetate can be, for example, from 10 % to 15 %, by weight, of the total weight of the composition.

In embodiments related to multi-layer microcapsules, the wall-forming material in each of the outer shells in the microcapsules described herein (e.g., a first wall- forming material of the inner core, a second wall-forming material of a first outer shell enveloping the inner core, and optionally a third wall-forming material of a second outer shell enveloping the first outer shell, and so forth) can be the same or different.

A fatty substance:

In some of any of the embodiments described herein, an outer shell optionally comprises a fatty substance as described herein in any one of the respective embodiments.

In some embodiments, the fatty substance is or comprises a fatty acid salt.

In some embodiments, a fatty acid salt comprises a long hydrophobic hydrocarbon chain (e.g., of 4 to 30 carbon atoms in length) carboxylate anion (a fatty acyl) and a cation, as depicted in the following formula:

(R-C(=0)-0^~)qM^(q+) wherein R is a substituted or unsubstituted, liner or branched hydrocarbon chain of 4 to 30 carbon atoms, M+ is a cation, preferably a metal cation, and q is an integer representing the number of fatty acyls that interact with the cation, and also represents the charge number of the cation (e.g., 1, 2, 3, etc.).

The fatty acid salts that are usable in some of any of the embodiments of the present invention may contain 1 to 3 fatty acyl chains, each chain, independently, comprising 4 to 30 or 8 to 24 carbon atoms (C8-C24) in length. Thus, the fatty acid salt can be a salt of a monovalent, divalent or trivalent metal ion or a salt of an organic cation.

A monovalent metal ion can be, for example, Na⁺, K⁺, Cs⁺, Li⁺; a divalent metal ion is selected from Mg²⁺, Ca²⁺, Fe (II), Co²⁺, Ni²⁺, Cu²⁺, Mn²⁺, Cd²⁺, Sr²⁺or Zn²⁺; a trivalent metal ion can be, for example, Fe(III), La³⁺, Eu³⁺ or Gd³⁺; an organic cation can be, for example, ammonium, sulfonium, phosphonium or arsonium.

The fatty acyl can be derived from fatty acids such as, but not limited to, stearic acid, arachidic acid, palmitoleic acid, oleic acid, linoleic acid, linolaidic acid, arachidonic acid, myristoleic acid and erucic acid. Other fatty acids are also contemplated.

Exemplary fatty acid salts include, but are not limited to, magnesium stearate, magnesium oleate, calcium stearate, calcium linoleate, sodium stearate, magnesium arachidonate, magnesium palmitate, magnesium linoleate, calcium arachidonate, calcium myristoleate, sodium linoleate, calcium linoleate, sodium stearate, potassium stearate, sodium laurate, sodium myristate, sodium palmitate, potassium laurate, potassium myristate, potassium palmitate, calcium laurate, calcium myristate, calcium palmitate, zinc laurate, zinc myristate, zinc palmitate, zinc stearate, magnesium laurate, and magnesium myristate.

In some embodiments, the fatty acid salt is magnesium stearate.

The fatty acid salt is usually in an amount within a range of from about 0.05 % to about 5 %, or from about 0.1 % to about 4.5 %, or from about 0.2 % to about 4 %, or from about 0.5 % to about 4 %, or from about 0.5 % to about 3.0 %, or from about 0.75 % to about 3.0 %, or from about 1.0 % to about 3.0 %, or from about 1.0 % to about 2.0 %, by weight, of the total microcapsule's weight, including any subranges and any intermediate values therebetween.

Without being bound by any particular theory, it is assumed that the cation of the fatty acid salt attracts the free carboxylic and/or hydroxyl groups of the wall- forming polymer, resulting in a better adhesion of the polymeric material to the inner core, thereby providing efficient encapsulation of the silicone material or any other material present in the inner core.

Fatty acid salts may be used in the preparation of single-layer microcapsules while being added to the organic phase together with the encapsulated material, and the wall-forming polymer. Upon contacting the organic phase with an aqueous phase, the fatty chains will spontaneously wrap around the encapsulated substance and their polar/ionic heads will interact with the oppositely charged groups on the polymer, thereby enhancing the formation of a polymeric envelope surrounding a core comprising the encapsulated material.

In some embodiments, the fatty substance is or comprises a glycolipid.

In some embodiments, the glycolipid is a fatty acid glycol ester, for example, a fatty acid ester of propylene glycol. The ester can be a monoester, a diester, a trimester, etc. The fatty acyl portion of the ester is as described herein.

In exemplary embodiments, the fatty substance is a propylene glycol monostearate.

In some of any of the embodiments described herein, the fatty substance further comprises a fatty acid as described herein, and/or fatty substances such as, for example, fatty esters, waxes, and oils.

The glycolipid is usually in an amount within a range of from about 0.1 % to about 20 %, or from about 0.1 % to about 15 %, or from about 1 % to about 15 %, or from about 1 % to about 10 %, or from about 5 % to about 10 %, by weight, of the total microcapsule's weight, including any subranges and any intermediate values therebetween.

Additional components:

In some of any of the embodiments described herein, the microcapsule further comprises additional components in the outer layer.

In some embodiments of any of the embodiments of the present invention, an outer shell of the microcapsules further comprises a plasticizer.

Herein and in the art, a "plasticizer" describes a substance which increases the plasticity or fluidity of a composition. In the context of the present embodiments, a plasticizer is added to the wall-forming material in order to control the physical properties and level of elasticity of the microcapsule's outer shells.

Exemplary plasticizers include, but are not limited to, triethyl citrate, tricaprylin, trilaurin, tripalmitin, triacetin, acetyltriethyl citrate, paraffin oil, and any combination thereof. In exemplary embodiments, the plasticizer is triethyl citrate. The amount of the plasticizer can be within a range of from about 0.5 % to about 30 %, or from about 0.5 % to about 20 %, or from about 1.0 % to about 20 %, or from about 5 % to about 15 %, or from about 5 % to about 10 %, or is about 10 % by weight, of the total weight of the microcapsule, including any subranges and any intermediate values therebetween.

The outer shell of the single-layer microcapsules described herein can be opaque, semi-opaque or non-opaque (transparent). In some embodiments, the outer shell is opaque.

In some embodiments, one or more of the outer shells of multi-layer microcapsules as described herein can be opaque, semi-opaque or non-opaque (transparent). In some embodiments, one or more of the outer shells (e.g., the most outer shell) is opaque.

In some embodiments of the present invention, opacity of the outer shell of the microcapsules is obtained by an inclusion of an opaque substance.

As used herein, an "opaque substance" is a substance which is non-transparent and blocks at least 70 % of the light passing therethrough.

Thus, an opaque outer shell blocks 70 % to 100 % of the light. Semi-opaque outer shell blocks up to 50 % of the light. Non-opaque or transparent outer shell blocks no more than 30 % of the light passing therethrough.

The terms "opacity" and "opaque" refer to herein to UV-vis light, such as, for example, daylight.

Exemplary opaque substances include, but are not limited to, Ti0₂, zinc oxide, alumina, boron nitride, talc, mica and any combination thereof.

The total amount of opaque substances in the outer shell is within a range of from about 1 % to about 50 %, or from about 1 % to about 40 %, or from about 10 % to about 40%, by weight, of the total weight of the microcapsule, including any subranges and any intermediate values therebetween.

In some of any of the embodiments described herein, the opaque substance is, or comprises, Ti0₂, and in some embodiments, an amount of Ti0₂ is within a range of from about 1 % to about 30 %, or from about 10 % to about 40 %, by weight, of the total weight of the microcapsule, including any subranges and any intermediate values therebetween. In some of any of the embodiments described herein, the opaque substance is, or comprises, Ti0₂, and in some embodiments, an amount of Ti0₂ is about 10 % by weight, of the total weight of the microcapsule.

In some of any of the embodiments described herein, the opaque substance is, or comprises, Ti0₂, and in some embodiments, an amount of Ti0₂ is about 35 % by weight, of the total weight of the microcapsule.

In some embodiments, the outer shell does not comprise an opaque substance as described herein.

In some embodiments, the outer shell comprises a dispersing agent, preferably a lower alkyl fatty acid ester such as, but not limited to, isopropyl myristate, isopropyl butyryl myristate, propylene glycol stearate, butylene glycol cocoate, hydrogenated lecithin and jojoba oil.

In some embodiments, the dispersing agent is isopropyl myristate (IPM), propylene glycol stearate, or a combination thereof.

The amount of a dispersing agent is usually within a range of from about 0.5 % to about 10 %, or from about 1 % to about 10 %, by weight, of the total weight of the multilayer microcapsule, including any subranges and any intermediate values therebetween.

In some of any of the embodiments described herein, the microcapsule, or at least the inner core is devoid of a monosaccharide material, for example, a monosaccharide-polyol such as mannitol, erythritol, xylitol, sorbitol and mixtures thereof.

In some of any of the embodiments described herein, the microcapsule, or at least the inner core, is devoid of mannitol.

Microcapsules Composition:

According to an aspect of some embodiments of the present invention there is provided a composition which comprises a plurality of microcapsules, at least a portion of the microcapsules are microcapsules which comprise an inner core comprising a silicone material, as described herein, and an outer shell (or two or more outer shells) formed of a wall-forming polymeric material enveloping the inner core, as described in any one of the embodiments described herein. In some embodiments, at least 10 %, at least 20 %, at least 30 %, at least 40 %, at least 50 %, at least 60 %, at least 70%, at least 80 %, at least 90 %, at least 95 %, at least 98 %, or at least 99 %, or substantially all of the plurality of microcapsules in the composition are microcapsules as described in any one of the embodiments described herein.

A "composition" as used herein refers to a plurality of microcapsules, which can be the same or different, which, when different, can feature a plurality or variety of features. In accordance with embodiments of the present invention, at least a portion of the plurality of microcapsules exhibits all the technical features characterizing a silicone material-encapsulating microcapsule as described herein, in any one of the embodiments thereof, for example, microcapsules encapsulating a silicone material, and being breakable upon rubbing on the skin.

A "composition" in the context of some of the present embodiments can be used as a raw material for making up a product, or formulation, as described herein.

According to an aspect of some embodiments of the present invention there is provided a plurality of microcapsules, at least a portion of the microcapsules are microcapsules which comprise an inner core comprising a silicone material, as described herein, and an outer shell (or two or more outer shells) comprised of a wall- forming polymeric material enveloping the inner core, as described in any one of the embodiments described herein.

The plurality of microcapsules can also be referred to herein interchangeably as a mixture comprising a plurality of microcapsules.

In some embodiments, at least 10 %, at least 20 %, at least 30 %, at least 40 %, at least 50 %, at least 60 %, at least 70%, at least 80 %, at least 90 %, at least 95 %, at least 98 %, or at least 99 %, or substantially all of the microcapsules in the plurality of microcapsules are microcapsules as described in any one of the embodiments described herein.

The term "at least a portion" means at least 20 %, at least 50 %, at least 70 %, at least 60 %, at least 80 %, at least 90 %, at least 95 %, at least 98 %, at least 99 % or all of the microcapsules being the single-layer, core-shell silicone material-encapsulating microcapsules, as described in any one of the respective embodiments herein. In some embodiments, the plurality of microcapsules as described herein can be the same, or can differ from one another by, for example, the silicone material encapsulated therein and/or the presence, and/or the type of wall-forming polymeric material comprising the outer shell and/or by the presence or absence of an opaque substance and/or by the presence or absence of a fatty substance and/or by the number of outer shells.

In some embodiments related to the composition or the plurality of microcapsules, a portion of the microcapsules can encapsulate a silicone material as described herein, and another portion of the microcapsules can encapsulate another, different, silicone material.

In some of any of the embodiments related to the composition or the plurality of microcapsules, one or more portions of the microcapsules can encapsulate one or more silicone materials, as described herein, optionally together with one or more other active agents, as described herein.

In some of any of the embodiments related to the composition or the plurality of microcapsules, one or more portions of the microcapsules can encapsulate one or more silicone materials, as described herein, and one or more portions of the plurality of microcapsules can encapsulate one or more other active agents, as described herein.

In some embodiments, a silicone material encapsulated in one portion of the microcapsules, and an active agent or another silicone material encapsulated in another portion of the microcapsules are incompatible with one another. By "incompatible" it is meant that the two or more of the different silicone materials and the additional active agents can react with one another when in contact, or do not maintain the stability and/or functionality when in contact with one another.

In some of the embodiments described herein for a microcapsules-containing composition or mixture which consists of microcapsules containing a silicone material as described herein, the average size of the microcapsules is within a range of from about 1 micron to about 1000 microns, or from about 1 micron to about 500 microns, or from about 1 microns to about 200 microns, or from about 10 microns to about 200 microns, or from about 50 microns to about 150 microns, including any subranges and intermediate values therebetween. Exemplary compositions:

In some exemplary embodiments of the present invention, the microcapsules as described herein comprise, as the inner core, a dimethicone featuring a viscosity in the range of 100 to 1100 centipoises, at room temperature.

In some of these embodiments, the amount of the inner core is at least 70 %, by weight, of the total weight of the microcapsules or of the composition, and is, for example, 70 %, or 79 %, or 80 %, or 85%, or 89 %, of the total weight of the microcapsule or of the composition.

In some exemplary embodiments of the present invention, the microcapsules are single-layer microcapsules, and the outer shell comprises magnesium stearate in an amount within a range of from 0.5 % to 1.5 %, by weight, of the total weight of the microcapsule.

In some of these embodiments, the amount of the wall-forming material ranges from 10 % to 15 %, by weight, of the total weight of the composition.

In some of these embodiments, the wall-forming material comprises a cellulose acetate.

In some exemplary embodiments of the present invention, the microcapsules are single-layer microcapsules, and do not comprise a fatty substance (e.g., a fatty acid salt).

In some of these embodiments, the wall-forming material comprises a cellulose ester such as cellulose acetate.

In some exemplary embodiments, a microcapsule as described herein is a single- layer microcapsule and comprises a silicone material as described herein in an amount of about 79-89 % by weight, a wall-forming polymer or copolymer in an amount of 10- 15 % by weight, and magnesium stearate in an amount of 0-1.5 %.

In some exemplary embodiments of any of the embodiments described herein, at least most, or all, of the microcapsules in a composition are single-layer microcapsules, and in some of these embodiments, for at least most, or for all, of the microcapsules in the composition, the outer shell comprises magnesium stearate in an amount within a range of from 0.5 % to 2.0 %, by weight, and, as a wall-forming material, a cellulose acetate, in an amount within a range of from 10 % to 15 %, by weight, of the total weight of the microcapsule or the composition. In some exemplary embodiments of any of the embodiments described herein, at least most, or all, of the microcapsules in a composition are single-layer microcapsules, and in some of these embodiments, for at least most, or for all, of the microcapsules in the composition, the outer shell does not comprise magnesium stearate, and comprises, as a wall-forming material, a cellulose acetate, in an amount within a range of 10 % to 15 %, by weight, of the total weight of the microcapsule or the composition.

In some exemplary embodiments of any of the embodiments described herein, at least most, or all, of the microcapsules in a composition are single-layer microcapsules, and in some of these embodiments, for at least most, or for all, of the microcapsules in the composition, the outer shell comprises propylene glycol monostearate in an amount within a range of from 5 % to 10 %, by weight.

The process:

The process used for the preparation of the microcapsules according to embodiments of the present invention is a modification of the microencapsulation solvent removal method disclosed, for example, in U.S. Patent Nos. 6,932,984 and 7,838,037 and WO 2012/156965, which are incorporated by reference as if fully set forth herein. According to this technology, the active ingredient is found in the core of the microcapsule. This technique seals each micro-capped ingredient from chemical and cross-link reactions, degradation, color change or loss of potency during production, and for extended periods in storage.

The solvent removal process is based on four main steps as follows:

(i) preparing a homogeneous organic solution comprising the encapsulated agent, and a wall-forming polymeric material, and optionally a fatty substance (and/or additional components such as a plasticizer), and an organic solvent that is partially miscible in water;

(ii) preparing an emulsion of an aqueous continuous phase containing an emulsifier and saturated with an organic solvent present in the organic solution, and optionally other ingredients;

(iii) mixing the homogeneous organic solution with the aqueous emulsion, under high shear stirring to thereby form an emulsion; and

(iv) extracting the organic solvent by contacting the emulsion formed in step (iii) with an extraction medium which comprises an amount of water which initiates extraction of the organic solvent from the emulsion, thereby obtaining the microcapsules.

For multi-layer (e.g., double-layer and triple-layer) microcapsules, the microcapsules are formed by first modifying the surface of the single-layer microcapsules formed according to steps (i)-(iv) and then subjecting the surface- modified inner core microcapsules to one or more cycles of steps (i)-(iv), when the inner core microcapsules are dispersed in the organic solution together with the wall- forming material.

In some embodiments, the microcapsules according to the present embodiments can be prepared by a modified solvent removal method comprising the following steps:

(a) contacting an organic phase comprising a silicone material, and a wall- forming polymer or copolymer, optionally a fatty substance (e.g., a fatty acid salt, a glycolipid), and optionally a plasticizer, and a partially water-miscible organic solvent (or mixture of solvents), with an aqueous solution saturated with at least one of organic solvents of the organic phase and comprising an emulsifier, to thereby obtain an emulsion; and

(b) contacting the formed emulsion with an extraction medium comprising water in an amount which initiates extraction of the organic solvent from the emulsion, thereby obtaining the microcapsules.

In further steps, the microcapsules are isolated (e.g., by centrifugation or decantation) following step (b), dried and sifted to thereby obtain a free flowing powder of the microcapsules.

These steps are further detailed as follows:

The homogenous solution prepared in step (a) is obtained by preparing an organic solution or dispersion of a wall-forming polymeric material as described in any one of the respective embodiments described herein, in an organic solvent that is partially miscible in water and is capable of dissolving or dispersing the wall-forming polymer. In exemplary embodiments, the organic solvent is an organic solvent approved for topical applications, such as, but not limited to, ethyl acetate, methyl acetate, ethanol, ethyl formate, or any combination thereof. In some embodiments, the organic solvent is ethyl acetate. The fatty substance is as described in any one of the respective embodiments described herein.

When a plasticizer is used, it is usually selected from tricaprylin, trilaurin, tripalmitin, triacetin, triethyl citrate, acetyltriethyl citrate, paraffin oil, or any combination thereof.

Optionally, an organic solution of the silicone material in an organic solvent is prepared and then the obtained solution is mixed with the polymer solution. The solvent can be the same or different. In some embodiments, the silicone material is mixed with methyl acetate.

The components of the organic solution are mixed/stirred until a homogeneous, optionally transparent, solution or dispersion is obtained.

The aqueous continuous phase is saturated with at least one of the organic solvents that form the organic solution, and typically comprises an emulsifier.

The organic solution or dispersion and the aqueous continuous phase are mixed under low sheer stirring to thereby form an emulsion.

In step (b), an extraction medium is contacted with the emulsion.

The emulsion can be added to the extraction medium, or the extraction medium can be added to the emulsion. The contacting can be performed gradually or at once.

In some embodiments, the extraction medium comprises water.

In some embodiments, the extraction medium further comprises an emulsifier, in an amount of, for example from 1 to 10 % by weight.

Upon contacting the emulsion prepared in (a), with the extraction medium, the organic solvent is extracted, thereby allowing the microcapsules to form.

In the context of embodiments of the invention, the term "low sheer stirring" refers to a mixing at about 100-800 rpm, preferably at about 300-600 rpm.

In some embodiments, when the microcapsules are multi-layer microcapsules, the process further comprises: (c) optionally repeating steps (a) and (b), using a second, third, and so on, organic phases and aqueous continuous phases, thereby obtaining multi-layered microcapsules. Additional active agents:

As described herein, the silicone-material encapsulating microcapsules of the present embodiments can further comprise an additional active agent, preferably in the inner core, but optionally also within the outer shell.

Alternatively, the compositions as described herein may comprise microcapsules encapsulating an active agent, other than a silicone material.

In any of these embodiments, the active agent (also referred to herein as active ingredient or active substance) may be an agent having biological activity (e.g., a pharmaceutically or dermatologically active agent, a cosmetic agent), an odor agent such as fragrances, a color agent such as a pigment and a colorant and/or volatile natural and synthetic compounds.

The agent having biological activity may be selected from vitamins, natural extracts, individual compounds isolated from natural sources or prepared synthetically, essential oils, and pharmaceutically active agents for topical or transdermal applications, as described herein.

Non-limiting examples of vitamins include vitamin A and its analogs and derivatives: retinol, retinal, retinyl palmitate, retinoic acid, tretinoin, iso-tretinoin (known collectively as retinoids), vitamin E (tocopherol and its derivatives), vitamin C (L-ascorbic acid and its esters and other derivatives), vitamin B₃ (niacinamide and its derivatives), alpha hydroxy acids (such as glycolic acid, lactic acid, tartaric acid, malic acid, citric acid, etc.) and beta hydroxy acids (such as salicylic acid and the like), and vitamins D, E, F, K, P, or mixtures thereof.

In some embodiments, the vitamin is vitamin A, either in its free form as Retinol or in its ester form as Retinol Palmitate. The most useable form of the vitamin is Retinol, the active form in the body. Retinol is an anti-oxidant vitamin used as nutritional factor and also as an active ingredient of topical/dental products. The activity of one IU (International Unit) of vitamin Ai (equivalent to a USP unit) is 0.3 μ g of all-trans Retinol. Retinol can be used for topical treatment of Ichthyosis vulgaris (an inherited skin disorder characterized by cornification of the skin) and common acne, and in anti-aging and rejuvenation formulations. However, Retinol (an unsaturated alcohol) is a small and unstable molecule and undergoes chemical degradation/oxidation due to its high potential for chemical reactions with other molecules and should be stabilized before using it as an active ingredient in compositions.

In order to enjoy the beneficial effects of Retinol and meet the shelf-life needed for topical/dental compositions, this active principle should be protected from oxidation. Encapsulation of Retinol by the single- or double-layered encapsulation method of the invention with an appropriate shell provides an effective solution for its stabilization and protection. The Retinol microcapsules of the invention are highly compatible with all types of topical/dental formulations and can be used in various applications including, without limiting, dental products, anti-aging products (creams, lotions, serums and masks), skin regeneration formulations, nourishing and moisturizing creams and anti-acne products.

In some embodiments, the vitamin is vitamin C (ascorbic acid), used in recent years as an active ingredient of cosmetics. Due to its antioxidant properties it is considered to confer both antioxidant and photoprotection to skin against free radical attack and UV ray damage. However, Vitamin C is easily oxidized and, upon storage, exposure to light, oxygen, moisture and/or high temperature, undergoes rapid degradation. It is unstable in aqueous solution, even under neutral pH and at room temperature. The microencapsulation of Vitamin C according to the present invention permits its use as active ingredient in cosmetic composition for use as moisturizing cream, anti-aging cream, anti-wrinkle cream, sunscreen cream, and for stimulating collagen production.

In some embodiments, the vitamin is vitamin E, preferably as a-tocopherol. Tocopherols (Vitamin E) are well-known for their antioxidant properties making vitamin E one of the most widely consumed vitamins. However, vitamin E in its ester form (e.g., tocopherol acetate) is only effective as antioxidant to the formulation, but not to the skin. To be effective as antioxidant to the skin, a tocopherol has to be used, but it is inherently unstable. The microcapsules of the invention preferably contain stable 25+1% a-tocopherol, and can be used in various types of cosmetic formulations such as sunscreen products, shampoos, conditioners, hair gels, liquid make-up and make-up tissue remover, and release about 95-97% of Vitamin E directly onto the skin/scalp upon application. In some embodiments, the vitamin is vitamin F, a mixture of unsaturated fatty acids essential for skin health and functionality, also known as Essential Fatty Acids (EFA; linoleic acid and alpha-linolenic acid.). Vitamin F oxidizes rapidly when incorporated in cosmetic formulation. The microencapsulation according to the invention offers a stable, active and odorless system of Vitamin F suitable for incorporation into moisturizing creams, anti-aging agents and anti-dryness serums. The microcapsules of the invention preferably contain stable 14±0.2% linolenic and linoleic free fatty acids a-tocopherol.

In some embodiments, the vitamin is Rutin (quercetin-3-rutinoside or vitamin PI), one of the most active natural flavanoids, highly effective as an antioxidant and free radical scavenger and in the treatment of cellulite due to its ability to control cross-linking of collagen synthesis. Rutin is widely applied in dermatological and cosmetic products due to its beneficial effects on the appearance of healthy skin and is well known for its potent antioxidant and anti- inflammatory properties and ability to strengthen and modulate the permeability of the walls of the blood vessels including capillaries.

However, when incorporated into cosmetic formulations in its non- encapsulated form, Rutin tends to react with other ingredients and oxidizes quickly, resulting in change of the original color of the formulation and loss of its original biological activity. In order to maintain its potent biological activity and prevent its oxidation in cosmetic formulations, Rutin should be stabilized. The Rutin microcapsules of the present invention, developed specifically for topical application in order to stabilize the Rutin, preferably contain a high concentration (about 7%) of pure Rutin Hydrate from plant source.

In some embodiments, the active ingredient having biological activity is a natural extract. In cosmetics, a natural extract is assumed to mean ingredients of botanical origin. To be truly natural it must be extracted from the relevant part of the plant without undergoing any significant chemical change.

This definition includes plant oils. Any herbal extract or plant oil used for topical application, for example in the cosmetic industry, can be used according to the invention, but preferred herbal extracts and plant oils for encapsulation according to the invention include Licorice root extract, Grape Seed extract, Borage oil, Evening Primrose oil and Hippophae oil.

In some embodiments, the natural extract is Grape Seed extract (GSE). GSE contains a high content of proanthocyanidins (also known as Oligomeric Proanthocyanidin Complexes or OPCs), a class of nutrients that belong to the flavonoid family and are potent antioxidants and free radical scavengers, reducing the harmful effects of UV radiation. In topical use, a great advantage of OPCs is a substantial increase in blood circulation at the sub-epitopical level and an improvement of intracellular membrane exchange of micronutrients.

The proanthocyanidins (OPCs), however, are not stable and oxidize rapidly due to temperature and light influence or cross-reactions with other ingredients of topical formulation. The brown color developed in the final product is a result of OPCs oxidation. Encapsulation of GSE according to the present invention prevents oxidative degradation and brown color development, since the polymeric microcapsule walls prevent interaction of Grape Seed extract with other ingredients of the formulation, as well as guarantees the maximum release of OPCs from capsules on the skin upon application with maximum biological affect. The microcapsules of the present invention contain natural GSE rich m proanthocyanidins (min. 95% OPC), preferably about 6% GSE, have a uniform spherical shape with an average size of about 40 microns, and increase the stability and shelf-life of the OPCs, maintain its original activity, and prevents the oxidation and color development in the cosmetic formulation. They are thus indicated as an active ingredient for incorporation in anti-aging creams, in after-sun creams for reduction of skin erythema, in moisturizing and revitalizing products, and in facial sunscreens for prevention of UV-induced lipid oxidation in skin.

In some embodiments, the natural extract is Licorice root extract rich in Glabridin, a flavanoid known for its beneficial effects on the skin due to its antiinflammatory and antioxidant properties. In addition, Glabridin has whitening/lightening and anti-spot properties, probably due to inhibition of tyrosinase and melanin synthesis. However, this extract tends to oxidize easily, resulting in a loss of Glabridin's original whitening activity. Moreover, Glabridin, as a flavanoid, is sensitive to pH changes and this factor is the reason for extreme instability of Glabridin in topical formulations, resulting in loss of its original activity and in the development of a dark brown color in formulations. The microcapsules of the present invention contain Licorice root extract rich in Glabridin. The product is standardized by a content of 4% Glabridin, which is protected by the microcapsules. These microcapsules provide stable lightening whitening agent, prevent oxidation of the Glabridin, thereby guaranteeing original activity of Glabridin and providing a longer shelf life of the end product; prevent development of brown color in formulations; are highly stable in a wide pH range; are freely dispersible in all types of cosmetic formulations; and provide a unique control release of the extract only upon application onto the skin. The Licorice Extract microcapsules of the invention are, therefore, indicated as an active ingredient in whitening creams and lotions, age- defying creams and serums, anti- spots treatment formulations and lightening hand creams.

In some embodiments, the natural extract is Borage oil, rich in essential fatty acids such as linoleic acid, gamma-linolenic acid (GLA), oleic acid and others, in their triglyceride form, and one of the most concentrated natural forms of GLA. Borage oil is not stable and its active components undergo degradation. The microcapsules of the invention contain about 25% odorless encapsulated Borage oil with increased stability and shelf-life, maintain the GLA in its non-degraded active form, prevent development of distinct malodor during storage of the product, prevent skin irritation, and afford controlled release of high percentage of Borage oil directly to the skin. These microcapsules are indicated as an active ingredient for incorporation in moisturizing creams (especially for dry skin), anti-aging creams, repair formulations, hand creams, and lip-gloss and lip-protecting products.

In some embodiments, the natural extract is Evening Primrose oil (EPO), rich in essential fatty acids such as linoleic acid, gamma-linolenic acid (GLA), oleic acid and others, in their triglyceride form. EPO is not stable and its active components undergo degradation. The microcapsules of the invention contain about 25% odorless encapsulated EPO with increased stability and shelf-life, maintain the GLA in its non-degraded active form, prevent development of distinct malodor during storage of the product, prevent skin irritation, and afford controlled release of high percentage of EPO directly to the skin. These microcapsules are indicated as an active ingredient for incorporation in moisturizing creams (especially for dry skin), anti-wrinkle formulation, repair formulations, hand creams, whitening products, lip-gloss and lip- protecting products.

In some embodiments, the natural extract is Sea Buckthorn (Hippophae rhamnoides) oil. This oil contains a unique mix of functional ingredients including a high concentration of carotenoids, palmitoleic acid, sito- sterols and derivatives of vitamins A and E, and is not stable. The microcapsules of the invention contain about 25% encapsulated natural Hippophae oil with increased stability and are indicated for incorporation as an active ingredient in anti-aging products, skin treatment formulations, e.g. after peeling, shaving, burns, etc., sunscreen products, eye-zone formulations, and after- sun products.

In some embodiments, the active substance encapsulated is an individual compound isolated from a natural source such as, but not limited to, a coumarin, a chalcone or a flavonoid selected from the group consisting of flavans, flavanols, flavonols, flavones, flavanones, isoflavones, anthocyanidins, and proanthocyanidins.

It should be understood that an active ingredient used in the present embodiments may belong to more than one category as defined herein. Thus, Rutin, defined above as Vitamin P, is a flavonoid, as well Glabridin of the Licorice root extract and the proanthocyanidins of the Grape Seed extract.

In some embodiments, the active substance encapsulated is an essential oil.

Essential oils are a class of volatile oils extracted from plants, fruits or flowers by steam, distillation or solvent extraction. Examples of essential oils that can be encapsulated according to the invention include Basil Essential Oil, Eucalyptus Essential Oil, Geranium Essential Oil, Grapefruit Essential Oil, Lemon Essential Oil, Peppermint Essential Oil, Tea Tree oil, or mixtures thereof.

In some embodiments, the essential oil is Tea Tree oil, an essential oil with a fresh camphoraceous odor, extracted from the leaves of the tree Melaleuca alternifolia. The oil has anti-inflammatory, antibacterial, antifungal, antiviral and antiparasitic properties. Tea Tree oil is beneficial in softening, regenerating and purifying the skin and scalp, in healing burns, disinfecting wounds and for treating spots and insect stings and bites. It is effective against fungal infections such as candidiasis, vaginal infections, fungal nail infections and for hemorrhoids. As a bath additive it may control bacteria in spas and pools. It is also known to reduce hypertrophic scarring and dandruff hair. Tea Tree Oil components include 1- terpinen-ol, responsible for most of the antimicrobial actions, 1 ,8-cineole, gamma terpinene, p-cymene and other terpenes. Tea Tree Oil is not stable and oxidizes and loses its original activity when incorporated in cosmetic formulations in its naked form, may cause skin irritation and has a very strong original odor due to its volatility.

The microcapsules of the present embodiments may contain about 5 % odorless encapsulated Tea Tree Oil with increased stability and shelf-life, preventing oxidation of unstable compounds and development of Tea Tree Oil's strong malodor in the formulation, and afford controlled release of high percentage of Tea Tree Oil directly to the skin/scalp. These microcapsules may be indicated as an active ingredient for incorporation in facial care formulations for sensitive and delicate skin, personal hygiene products and shampoos for damaged and delicate hair, and anti- dandruff shampoos.

In some embodiments, the active ingredient encapsulated is an odor (usually a pleasant odor) agent such as fragrances, perfumes, essential oils and compounds extracted therefrom, and volatile natural and synthetic compounds. These agents can be used to impart a pleasant odor to the cosmetic formulation and/or to mask an undesired odor of other components of the formulation.

Agents with odor properties are widely used in topical products. Typically, these agents such as fragrances, perfumes and other volatile materials suffer from instability under specific conditions such as pH of the formulation or they cross- react with other ingredients of the formulation. For these reasons, it is necessary to encapsulate this type of ingredients.

In some embodiments, the volatile compound is Menthol, a monocyclic terpene alcohol obtained from peppermint oil or other mint oils, or prepared synthetically by hydrogenation of thymol. Menthol is a white crystal with a characteristic refreshing mint odor, which provides cosmetic formulations with a fresh sensation, cooling effect, calming qualities and short-term relief. However, Menthol, as a volatile ingredient, has a tendency to evaporate and to change the original content/odor of the formulation. In addition, it is difficult to disperse. Menthol homogeneously in cosmetic formulations and usually requires predispersion with ethanol. The precipitation of Menthol from the formulations, its original strong characteristic odor and its potential cross-linking with other ingredients, are reasons that difficult its use in topical/dental products. The odorless Menthol microcapsules may contain about 10 % Menthol. The microcapsules protect the Menthol from oxidation and maintain its original activity after incorporation into cosmetic formulations. They mask Menthol's characteristic odor while maintaining the original smell, preventing it from reacting with other ingredients in the formulation and providing a long lasting sensation/cooling effect upon application on skin. These microcapsules can be homogeneously dispersed in cosmetic formulations without requiring the use of alcohol and are, therefore, indicated as an ingredient for oral hygiene care, e.g. toothpastes, mouth rinses, sun- screen products, cooling after- sun lotions, calming creams and refreshing pre- and after- shave products.

In some of any of the embodiments described herein, the active ingredient encapsulated is a colorant.

The terms "colorant", "color agent" and "pigment" are used herein interchangeably and refer to organic pigments such as synthetic or natural dyes selected from any of the well known FD&C or D&C dyes, inorganic pigments such as metal oxides, or lakes and any combination (blend) thereof. In some exemplary embodiments, the color agent is an inorganic pigment, such as, for example, a metal oxide.

The colorant may be oil- soluble or oil-dispersible or with limited solubility in water. Typically suitable colorants for microencapsulation according to some of any of the embodiments of the present invention include, but are not limited to, organic and inorganic pigments, lakes, natural and synthetic dyes and any combination thereof.

In some embodiments, the color agents are inorganic pigments such as, but not limited to, metal oxides such as iron oxides, titanium dioxide (Ti0₂), titanium lower oxides, aluminum oxide, zirconuim oxides, cobalt oxides, cerium oxides, nickel oxides, chromium oxide (chromium green), zinc oxide and composite metal oxides; metal hydroxides such as calcium hydroxide, iron hydroxides, aluminum hydroxide, chromium hydroxide, magnesium hydroxide and composite metal hydroxides; other colorants such as ferric ammonium ferrocyanide, Prussian blue, iron sulfides, manganese violet, carbon black, mica, kaolin, and any combination thereof.

In some of any of these embodiments, the inorganic pigments are selected from iron oxides, titanium dioxide, zinc oxide, chromium oxide/hydroxide, and mixtures thereof. In a more preferred embodiment, the color agent is iron oxide of any one of the three primary colors- red, yellow or black, or most preferably, a mixture thereof. Optionally, the colorant may comprise, besides the mixture of iron oxides, titanium dioxide, for the purpose of providing any desired final color or shade of color to the composition. Preferably, when encapsulated within the inner core microcapsules, titanium dioxide is used in any one of its mineral forms such as, but not limited to, anatase, brookite or rutile, or any combination thereof.

In some other embodiment, the colorants are Lake organic pigments produced by precipitation of a natural or synthetic dye with a metallic salt such as aluminum, calcium or barium salts. Such colorants are typically oil-dispersible and widely used in cosmetics. Examples of Lake pigments include, but are not limited to, Indigo Lakes, Carmine Lakes, lakes from the series of the well-known FD&C and D&C dyes such as D&C Red 21 Aluminum Lake, D&C Red 7 Calcium Lake.

In some embodiments, the colorant is a reflective agent.

Exemplary reflective agents include, but are not limited to, bismuth oxychloride, inorganic nacres, particles with metallic glint, micas and other inorganic pigments, and combination thereof.

Iinorganic pigments that are usable in the context of these embodiments of the present invention include, but are not limited to, titanium oxides, zirconium oxides, cerium oxides, zinc oxides, iron oxides, chromium oxides, ferric blue, manganese violet, ultramarine blue and chromium hydrate.

Additional pigments that are usable in the context of these embodiments of the present invention include, but are not limited to, pigment structures of the sericite/brown iron oxide/titanium dioxide/silica type, or of BaS0₄/Ti0₂/FeS0₃ type, of silica/iron oxide type, or silica microspheres containing iron oxide.

The term "nacres" describes iridescent or non-iridescent colored particles, either of a natural origin (e.g., produced by certain molluscs in their shell) or synthesized, which exhibit a color effect by featuring optical interference. The term "nacres" is also referred to herein as "nacreous pigments".

Exemplary nacreous pigments include, but are not limited to, titanium mica coated with an iron oxide, titanium mica coated with bismuth oxychloride, titanium mica coated with chromium oxide, titanium mica coated with an organic dye and also nacreous pigments based on bismuth oxychloride. These may also be mica particles at the surface of which are superposed at least two successive layers of metal oxides and/or of organic colorants.

Additional exemplary nacres include, but are not limited to, natural mica coated with titanium oxide, with iron oxide, with natural pigment or with bismuth oxychloride.

Commercially available nacres include, for example, the Timica, Flamenco and Duochrome (mica-based) nacres sold by the company BASF, the Timiron nacres sold by the company Merck, the Prestige mica-based nacres sold by the company Eckart, the following nacres based on natural mica: Sunpearl from the company Sun Chemical, KTZ from the company Kobo and Sunprizma from the company Sun Chemical, the Sunshine and Sunprizma nacres based on synthetic mica sold by the company Sun Chemical, and the Timiron Synwhite nacres based on synthetic mica sold by the company MERCK.

More particular examples include gold-colored nacres sold especially by the company BASF under the name Brilliant gold 212G (Timica), Gold 222C (Cloisonne), Sparkle gold (Timica), Gold 4504 (Chromalite) and Monarch gold 233X (Cloisonne); the bronze nacres sold especially by the company Merck under the names Bronze fine (17384) (Colorona) and Bronze (17353) (Colorona) and by the company BASF under the name Super bronze (Cloisonne); the orange nacres sold especially by the company BASF under the names Orange 363C (Cloisonne) and Orange MCR 101 (Cosmica) and by the company Merck under the names Passion orange (Colorona) and Matte orange (17449) (Microna); the brown-tinted nacres sold especially by the company BASF under the names Nuantique copper 340XB (Cloisonne) and Brown CL4509 (Chromalite); the nacres with a copper tint sold especially by the company BASF under the name Copper 340A (Timica); the nacres with a red tint sold especially by the company Merck under the name Sienna fine (17386) (Colorona); the nacres with a yellow tint sold especially by the company BASF under the name Yellow (4502) (Chromalite); the red-tinted nacres with a golden tint sold especially by the company BASF under the name Sunstone G012 (Gemtone); the pink nacres sold especially by the company BASF under the name Tan opale G005 (Gemtone); the black nacres with a golden tint sold especially by the company BASF under the name Nu antique bronze 240 AB (Timica); the blue nacres sold especially by the company Merck under the name Matte blue (17433) (Microna); the white nacres with a silvery tint sold especially by the company Merck under the name Xirona Silver; and the golden-green pinkish- orange nacres sold especially by the company Merck under the name Indian summer (Xirona), and mixtures thereof.

Exemplary particles with a metallic glint which are usable in the context of the present embodiments include, but are not limited to, particles of at least one metal and/or of at least one metal derivative, particles comprising a single-material or multi- material organic or inorganic substrate, at least partially coated with at least one layer with a metallic glint comprising at least one metal and/or at least one metal oxide, metal halide or metal sulfide, and mixtures of said particles.

Exemplary metals that may be present in such particles include, but are not limited to, Ag, Au, Cu, Al, Ni, Sn, Mg, Cr, Mo, Ti, Zr, Pt, Va, Rb, W, Zn, Ge, Te and Se, and mixtures or alloys thereof, preferably Ag, Au, Cu, Al, Zn, Ni, Mo and Cr and mixtures or alloys thereof.

Exemplary particles with metallic glint include, but are not limited to, aluminum particles, such as those sold under the names Starbrite 1200 EAC® by the company Siberline and Metalure® by the company Eckart; particles made of metal powders of copper or of alloy mixtures such as the references 2844 sold by the company Radium Bronze, metallic pigments, for instance aluminium or bronze, such as those sold under the names Rotosafe 700 from the company Eckart, silica-coated aluminium particles sold under the name Visionaire Bright Silver from the company Eckart, and metal alloy particles, for instance the silica-coated bronze (alloy of copper and zinc) powders sold under the name Visionaire Bright Natural Gold from the company Eckart.

Other particles are those comprising a glass substrate such as those sold by the company Nippon Sheet Glass under the names Microglass Metashine, Xirona from the company Merck, Ronastar from the company Merck, Reflecks from the company BASF and Mirage from the company BASF. Additional exemplary reflective agents include, goniochromatic coloring agents such as, for example, multilayer interference structures and liquid-crystal coloring agents.

Other reflective agents would be readily recognized by those skilled in the art. As described herein, the colorant can be included in the inner core of the microcapsules. Alternatively, a colorant can be included within an outer shell of microcapsules, either microcapsules encapsulating a silicone material, as described herein, or other microcapsules in a composition as described herein.

Exemplary additional active agents according to embodiments of present invention include, without limitation, one or more, or any combination of an antibiotic agent, an antimicrobial agent, an anti-acne agent, an anti-aging agent, a wrinkle- reducing agent, a skin whitening agent, a sebum reducing agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a nonsteroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, an antineoplastic agent, an immunomodulator, an interferon, an antidepressant, an anti histamine, a hormone and an anti-dandruff agent.

Examples of these include alpha-hydroxy acids and esters, beta-hydroxy acids and ester, polyhydroxy acids and esters, kojic acid and esters, ferulic acid and ferulate derivatives, vanillic acid and esters, dioic acids (such as sebacid and azoleic acids) and esters, retinol, retinal, retinyl esters, hydroquinone, t-butyl hydroquinone, mulberry extract, licorice extract, and resorcinol derivatives.

Suitable anti-acne agents for use in this context of the present invention include, without limitation, keratolytics such as salicylic acid, sulfur, glycolic, pyruvic acid, resorcinol, and N-acetylcysteine and retinoids such as retinoic acid and its derivatives (e.g., cis and trans, esters).

Suitable antibiotics for use in this context of the present invention include, without limitation, benzoyl peroxide, octopirox, erythromycin, zinc, tetracyclin, triclosan, azelaic acid and its derivatives, phenoxy ethanol and phenoxy proponol, ethylacetate, clindamycin and meclocycline; sebostats such as flavinoids; alpha and beta hydroxy acids; and bile salts such as scymnol sulfate and its derivatives, deoxycholate and cholate. Representative examples of non-steroidal anti-inflammatory agents that are usable in this context of the present invention include, without limitation, oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP- 14,304; salicylates, such as aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal; acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, and ketorolac; fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic, and tolfenamic acids; propionic acid derivatives, such as ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofenic; pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone, azapropazone, and trimethazone. Mixtures of these nonsteroidal anti-inflammatory agents may also be employed, as well as the dermatologically acceptable salts and esters of these agents. For example, etofenamate, a flufenamic acid derivative, is particularly useful for topical application.

Representative examples of steroidal anti-inflammatory drugs include, without limitation, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionates, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylesters, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone, fludrocortisone, diflurosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone and the balance of its esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, diflurprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, triamcinolone, and mixtures thereof. Suitable antipruritic agents include, without limitation, pharmaceutically acceptable salts of methdilazine and trimeprazine.

Non-limiting examples of anesthetic drugs that are suitable for use in context of the present invention include pharmaceutically acceptable salts of lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine and phenol.

Suitable antimicrobial agents, including antibacterial, antifungal, antiprotozoal and antiviral agents, for use in context of the present invention include, without limitation, beta-lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, erythromycin, amikacin, triclosan, doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, metronidazole, pentamidine, gentamicin, kanamycin, lineomycin, methacycline, methenamine, minocycline, neomycin, netilmicin, streptomycin, tobramycin, and miconazole. Also included are tetracycline hydrochloride, farnesol, erythromycin estolate, erythromycin stearate (salt), amikacin sulfate, doxycycline hydrochloride, chlorhexidine gluconate, chlorhexidine hydrochloride, chlortetracycline hydrochloride, oxytetracycline hydrochloride, clindamycin hydrochloride, ethambutol hydrochloride, metronidazole hydrochloride, pentamidine hydrochloride, gentamicin sulfate, kanamycin sulfate, lineomycin hydrochloride, methacycline hydrochloride, methenamine hippurate, methenamine mandelate, minocycline hydrochloride, neomycin sulfate, netilmicin sulfate, paromomycin sulfate, streptomycin sulfate, tobramycin sulfate, miconazole hydrochloride, amanfadine hydrochloride, amanfadine sulfate, triclosan, octopirox, parachlorometa xylenol, nystatin, tolnaftate and clotrimazole and mixtures thereof.

Non-limiting examples of anti-oxidants that are usable in the context of the present invention include ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and their salts, 6- hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available under the trade name Trolox ), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., N,N- diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (e.g., glutathione), dihydroxy fumaric acid and its salts, lycine pidolate, arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine, proline, superoxide dismutase, silymarin, tea extracts, grape skin/seed extracts, melanin, and rosemary extracts.

Non-limiting examples of antineoplastic agents usable in context of the present invention include daunorubicin, doxorubicin, idarubicin, amrubicin, pirarubicin, epirubicin, mitoxantrone, etoposide, teniposide, vinblastine, vincristine, mitomycin C, 5-FU, paclitaxel, docetaxel, actinomycin D, colchicine, topotecan, irinotecan, gemcitabine cyclosporin, verapamil, valspodor, probenecid, MK571, GF120918, LY335979, biricodar, terfenadine, quinidine, pervilleine A and XR9576.

Non-limiting examples of antidepressants usable in context of the present invention include norepinephrine-reuptake inhibitors ("NRIs"), selective-serotonin- reuptake inhibitors (SSRIs), monoamine-oxidase inhibitors (MAOIs), serotonin-and- noradrenaline-reuptake inhibitors ("SNFIs), corticotropin-releasing factor (CRF) antagonists, a-adrenoreceptor antagonists, NKl-receptor antagonists, 5-HTi_A-receptor agonist, antagonists, and partial agonists and atypical antidepressants, as well as norepinephrine -reuptake inhibitors such as, but are not limited to amitriptyline, desmethylamitriptyline, clomipramine, doxepin, imipramine, imipramine-oxide, trimipramine; adinazolam, amiltriptylinoxide, amoxapine, desipramine, maprotiline, nortriptyline, protriptyline, amineptine, butriptyline, demexiptiline, dibenzepin, dimetacrine, dothiepin, fluacizine, iprindole, lofepramine, melitracen, metapramine, norclolipramine, noxiptilin, opipramol, perlapine, pizotyline, propizepine, quinupramine, reboxetine, tianeptine, and serotonin-reuptake inhibitors such as, but are not limited to, binedaline, m-chloropiperzine, citalopram, duloxetine, etoperidone, femoxetine, fluoxetine, fluvoxamine, indalpine, indeloxazine, milnacipran, nefazodone, oxaflazone, paroxetine, prolintane, ritanserin, sertraline, tandospirone, venlafaxine and zimeldine.

Exemplary anti-dandruff agents include, without limitation, zinc pyrithione, shale oil and derivatives thereof such as sulfonated shale oil, selenium sulfide, sulfur; salicylic acid, coal tar, povidone-iodine, imidazoles such as ketoconazole, dichlorophenyl imidazolodioxalan, clotrimazole, itraconazole, miconazole, climbazole, tioconazole, sulconazole, butoconazole, fluconazole, miconazolenitrite and any possible stereo isomers and derivatives thereof such as anthralin, piroctone olamine (Octopirox), selenium sulfide, and ciclopirox olamine, and mixtures thereof.

Non-limiting examples of dermatological active ingredients usable in context of the present invention include jojoba oil and aromatic oils such as methyl salicylate, wintergreen, peppermint oil, bay oil, eucalyptus oil and citrus oils, as well as ammonium phenolsulfonate, bismuth subgallate, zinc phenolsulfonate and zinc salicylate. Non-limiting examples of antifungal agents include miconazole, clotrimazole, butoconazole, fenticonasole, tioconazole, terconazole, sulconazole, fluconazole, haloprogin, ketonazole, ketoconazole, oxinazole, econazole, itraconazole, terbinafine, nystatin and griseofulvin.

Non-limiting examples of antihistamines usable in context of the present invention include chlorpheniramine, brompheniramine, dexchlorpheniramine, tripolidine, clemastine, diphenhydramine, promethazine, piperazines, piperidines, astemizole, loratadine and terfenadine.

It is to be noted that any other active agent, including agents described herein as additives, can be encapsulated in the microcapsules as described herein.

As described herein, the active agent can be included in the inner core of the microcapsules and/or in the outer layer.

Topical Formulations:

As discussed hereinabove, the silicone material-encapsulating microcapsules as described herein are particularly usable for inclusion in topical formulations, particularly cosmetic or cosmeceutical formulations and products.

In some embodiments, the composition provided herein is used in cosmetic, cosmeceutical or pharmaceutical formulations or products such as skin care formulations or products, make-up or dermatological or other topical pharmaceutical formulations or products, comprising the microcapsules as described herein (e.g., a color composition as described herein). The formulation can optionally and preferably further comprise a carrier, and optionally additional active agents and/or additives.

As used herein, a "formulation" refers to a vehicle in the form of emulsion, lotion, cream, gel, powder, etc., that comprises the microcapsules as described herein with physiologically acceptable carriers and excipients and optionally other chemical components such as cosmetic, cosmeceutical or pharmaceutical agents (e.g., drugs). As used herein, the term "physiologically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia (e.g., for topical use) in animals, and more particularly in humans.

Herein, the phrase "physiologically suitable carrier" refers to an approved carrier or a diluent that does not cause significant irritation to an organism at least upon topical application and does not abrogate the biological activity and properties of a possible active agent. This phrase encompasses dermatologically acceptable carriers, as these are known or recognized in the art.

Herein, the term "excipient" refers to an inert substance added to a pharmaceutical composition to further facilitate processes and administration of the active ingredients.

In some embodiment of the present invention, the cosmetic or cosmeceutical formulation is formulated in a form suitable for topical application on the applied area (e.g., a keratinous tissue, for example, facial skin).

By selecting the appropriate carrier and optionally other ingredients that can be included in the composition, as is detailed hereinbelow, the compositions of the present embodiments may be formulated into any form typically employed for topical application.

By "appropriate carrier" for topical application it is meant any medium compatible with a keratinous substrate, which has a color, a smell and a pleasant feel and which does not generate unacceptable discomfort (stinging, tautness or redness).

The phrase "keratinous material" or "keratinous substrate" or "keratinous tissue" means, in some embodiments of the present invention, hair or skin and especially areas like the face, cheeks, hands, body, legs, around the eyes, the eyelids and the lips.

"Skin" means the outermost protective covering of mammals that is composed of cells such as keratinocytes, fibroblasts and melanocytes. Skin includes an outer epidermal layer and an underlying dermal layer. Skin may also include hair and nails as well as other types of cells commonly associated with skin, such as, for example, myocytes, Merkel cells, Langerhans cells, macrophages, stem cells, sebocytes, nerve cells and adipocytes. "Skin-care" means regulating and/or improving a skin condition. Some non- limiting examples include improving skin appearance and/or feel by providing a smoother, more even appearance and/or feel; increasing the thickness of one or more layers of the skin; improving the elasticity or resiliency of the skin; improving the firmness of the skin; and reducing the oily, shiny, and/or dull appearance of skin, improving the hydration status or moisturization of the skin, improving the appearance of fine lines and/or wrinkles, improving skin exfoliation or desquamation, plumping the skin, improving skin barrier properties, improve skin tone, reducing the appearance of redness or skin blotches, and/or improving the brightness, radiancy, or translucency of skin.

"Skin-care active" means a compound or combination of compounds that, when applied to skin, provide an acute and/or chronic benefit to skin or a type of cell commonly found therein. Skin-care actives may regulate and/or improve skin or its associated cells (e.g., improve skin elasticity; improve skin hydration; improve skin condition; and improve cell metabolism).

"Skin-care formulation" means a formulation that includes a skin-care active and regulates and/or improves skin condition.

"Skin-care product" as used herein refers to a product that includes a skin-care composition or formulation. Some non-limiting examples of "skin-care products" include skin creams, moisturizers, lotions, and body washes.

"Topical application" means to apply or spread the formulation, composition or product of the present embodiments onto the surface of the keratinous tissue.

The formulations can be water-based, oil-based, emulsion-based (including water-in-oil, oil-in-water, water-in-oil-in-water and oil-in-water-in-oil emulsions) or silicon-based.

The formulations as described herein can be, for example, skin care products, make-up products (including eye shadows, make-up, lipstick, lacquer, etc.), men's grooming products, sunscreen products, hair care products, or any other product as described herein.

In some embodiments, a formulation as described is in a form of a cream, an ointment, a paste, a gel, a lotion, a milk, an oil, a suspension, a solution, an aerosol, a spray, a foam, a powder (e.g., a pressed powder or a loose powder) or a mousse. Ointments are semisolid preparations, typically based on petrolatum or petroleum derivatives. The specific ointment base to be used is one that provides for optimum delivery for the active agent chosen for a given formulation, and, preferably, provides for other desired characteristics as well (e.g., emolliency). As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and nonsensitizing. As explained in Remington: The Science and Practice of Pharmacy, 19th Ed., Easton, Pa.: Mack Publishing Co. (1995), pp. 1399-1404, ointment bases may be grouped in four classes: oleaginous bases; emulsifiable bases; emulsion bases; and water-soluble bases. Oleaginous ointment bases include, for example, vegetable oils, fats obtained from animals, and semisolid hydrocarbons obtained from petroleum.

Emulsifiable ointment bases, also known as absorbent ointment bases, contain little or no water and include, for example, hydroxystearin sulfate, anhydrous lanolin and hydrophilic petrolatum. Emulsion ointment bases are either water-in-oil (W/O) emulsions or oil-in-water (O/W) emulsions, and include, for example, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid. Preferred water-soluble ointment bases are prepared from polyethylene glycols of varying molecular weight.

Lotions are preparations that are to be applied to the skin surface without friction. Lotions are typically liquid or semiliquid preparations in which solid particles, including the sunscreens-containing microcapsules, are present in a water or alcohol base. Lotions are typically preferred for covering/protecting large body areas, due to the ease of applying a more fluid composition. Lotions are typically suspensions of solids, and oftentimes comprise a liquid oily emulsion of the oil-in-water type. It is generally necessary that the insoluble matter in a lotion be finely divided. Lotions typically contain suspending agents to produce better dispersions as well as compounds useful for localizing and holding the active agent in contact with the skin, such as methylcellulose, sodium carboxymethyl-cellulose, and the like.

Creams are viscous liquids or semisolid emulsions, either oil-in-water or water- in-oil. Cream bases are typically water-washable, and contain an oil phase, an emulsifier and an aqueous phase. The oil phase, also called the "internal" phase, is generally comprised of petrolatum and/or a fatty alcohol such as cetyl or stearyl alcohol. The aqueous phase typically, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant. The emulsifier in a cream formulation is generally a nonionic, anionic, cationic or amphoteric surfactant. Reference may be made to Remington: The Science and Practice of Pharmacy, supra, for further information.

Pastes are semisolid dosage forms in which the bioactive agent is suspended in a suitable base. Depending on the nature of the base, pastes are divided between fatty pastes or those made from a single-phase aqueous gels. The base in a fatty paste is generally petrolatum, hydrophilic petrolatum and the like. The pastes made from single- phase aqueous gels generally incorporate carboxymethylcellulose or the like as a base. Additional reference may be made to Remington: The Science and Practice of Pharmacy, for further information.

Gel formulations are semisolid, suspension-type systems. Single-phase gels contain organic macromolecules distributed substantially uniformly throughout the carrier liquid, which is typically aqueous, but also, preferably, contain an alcohol and, optionally, an oil. Preferred organic macromolecules, i.e., gelling agents, are crosslinked acrylic acid polymers such as the family of carbomer polymers, e.g., carboxypolyalkylenes that may be obtained commercially under the trademark Carbopol™. Other types of preferred polymers in this context are hydrophilic polymers such as polyethylene oxides, polyoxyethylene-polyoxypropylene copolymers and polyvinylalcohol; cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and methyl cellulose; gums such as tragacanth and xanthan gum; sodium alginate; and gelatin. In order to prepare a uniform gel, dispersing agents such as alcohol or glycerin can be added, or the gelling agent can be dispersed by trituration, mechanical mixing or stirring, or combinations thereof.

Sprays generally provide the active agent in an aqueous and/or alcoholic solution which can be misted onto the skin for delivery. Such sprays include those formulated to provide for concentration of the active agent solution at the site of administration following delivery, e.g., the spray solution can be primarily composed of alcohol or other like volatile liquid in which the active agent can be dissolved. Upon delivery to the skin, the carrier evaporates, leaving concentrated active agent at the site of administration.

Foam compositions are typically formulated in a single or multiple phase liquid form and housed in a suitable container, optionally together with a propellant which facilitates the expulsion of the composition from the container, thus transforming it into a foam upon application. Other foam forming techniques include, for example the "Bag-in-a-can" formulation technique. Compositions thus formulated typically contain a low-boiling hydrocarbon, e.g., isopropane. Application and agitation of such a composition at the body temperature cause the isopropane to vaporize and generate the foam, in a manner similar to a pressurized aerosol foaming system. Foams can be water- based or hydroalcoholic, but are typically formulated with high alcohol content which, upon application to the skin of a user, quickly evaporates, driving the active ingredient through the upper skin layers to the site of treatment.

The preparation of the formulation can be carried out by mixing and homogenizing all the ingredients except for the reflective agent-encapsulating microcapsules, and adding the microcapsules at the end, followed by low shear mixing of the mixture.

The microcapsules of the invention can be used in pharmaceutical compositions for topical application, which include, for example, pharmaceutically active agents for dermatological or transdermal applications.

In any of the formulations described herein, additional agents and/or additives can be included. These agents and/or additives and can be encapsulated or non- encapsulated.

In some embodiments, one or more of these agents and/or additives is encapsulated.

In some of these embodiments, the agents and/or additives are encapsulated using microcapsules as described in any one of U.S. Patent Nos. 6,932,984 and 7,838,037, and WO 2009/138978.

Some non-limiting representative examples of additives and/or agents include humectants, deodorants, antiperspirants, sunscreen agents (e.g, UV blocking agents, UV filters), sunless tanning agents, hair conditioning agents, pH adjusting agents, chelating agents, preservatives, emulsifiers, occlusive agents, emollients, thickeners, solubilizing agents, penetration enhancers, anti-irritants, colorants, propellants and surfactants.

Representative examples of humectants include, without limitation, guanidine, glycolic acid and glycolate salts (e.g. ammonium slat and quaternary alkyl ammonium salt), aloe vera in any of its variety of forms (e.g., aloe vera gel), allantoin, urazole, polyhydroxy alcohols such as sorbitol, glycerol, hexanetriol, propyleneglycol, butylene glycol, hexylene glycol and the like, polyethylene glycols, sugars and starches, sugar and starch derivatives (e.g., alkoxylated glucose), hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine and any combination thereof.

Suitable pH adjusting agents include, for example, one or more of adipic acids, glycines, citric acids, calcium hydroxides, magnesium aluminometasilicates, buffers or any combinations thereof.

Representative examples of deodorant agents include, without limitation, quaternary ammonium compounds such as cetyl-trimethylammonium bromide, cetyl pyridinium chloride, benzethonium chloride, diisobutyl phenoxy ethoxy ethyl dimethyl benzyl ammonium chloride, sodium N-lauryl sarcosine, sodium N-palmithyl sarcosine, lauroyl sarcosine, N-myristoyl glycine, potassium N-lauryl sarcosine, stearyl, trimethyl ammonium chloride, sodium aluminum chlorohydroxy lactate, tricetylmethyl ammonium chloride, 2,4,4'-trichloro-2'-hydroxy diphenyl ether, diaminoalkyl amides such as L-lysine hexadecyl amide, heavy metal salts of citrate, salicylate, and piroctose, especially zinc salts, and acids thereof, heavy metal salts of pyrithione, especially zinc pyrithione and zinc phenolsulfate.

Other deodorant agents include, without limitation, odor absorbing materials such as carbonate and bicarbonate salts, e.g. as the alkali metal carbonates and bicarbonates, ammonium and tetraalkylammonium carbonates and bicarbonates, especially the sodium and potassium salts, or any combination of the above.

Antiperspirant agents can be incorporated in the compositions of the present invention either in a solubilized or a particulate form and include, for example, aluminum or zirconium astringent salts or complexes.

Representative examples of sunless tanning agents include, without limitation, dihydroxyacetone, glyceraldehyde, indoles and their derivatives. The sunless tanning agents can be used in combination with the sunscreen agents.

The chelating agents are optionally added to formulations so as to enhance the preservative or preservative system. Preferred chelating agents are mild agents, such as, for example, ethylenediaminetetraacetic acid (EDTA), EDTA derivatives, or any combination thereof. Suitable preservatives include, without limitation, one or more alkanols, disodium EDTA (ethylenediamine tetraacetate), EDTA salts, EDTA fatty acid conjugates, isothiazolinone, parabens such as methylparaben and propylparaben, propyleneglycols, sorbates, urea derivatives such as diazolindinyl urea, or any combinations thereof.

Suitable emulsifiers include, for example, one or more sorbitans, alkoxylated fatty alcohols, alkylpolyglycosides, soaps, alkyl sulfates, monoalkyl and dialkyl phosphates, alkyl sulphonates, acyl isothionates, or any combinations thereof.

Suitable occlusive agents include, for example, petrolatum, mineral oil, beeswax, silicone oil, lanolin and oil-soluble lanolin derivatives, saturated and unsaturated fatty alcohols such as behenyl alcohol, hydrocarbons such as squalane, and various animal and vegetable oils such as almond oil, peanut oil, wheat germ oil, linseed oil, jojoba oil, oil of apricot pits, walnuts, palm nuts, pistachio nuts, sesame seeds, rapeseed, cade oil, corn oil, peach pit oil, poppyseed oil, pine oil, castor oil, soybean oil, avocado oil, safflower oil, coconut oil, hazelnut oil, olive oil, grape seed oil and sunflower seed oil.

Suitable emollients include, for example, dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG Ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof and mixtures thereof.

Suitable thickeners include, for example, non-ionic water-soluble polymers such as hydroxyethylcellulose (commercially available under the Trademark Natrosol® 250 or 350), cationic water-soluble polymers such as Polyquat 37 (commercially available under the Trademark Synthalen® CN), fatty alcohols, fatty acids and their alkali salts and mixtures thereof.

Representative examples of solubilizing agents that are usable in this context of the present invention include, without limitation, complex-forming solubilizers such as citric acid, ethylenediamine-tetraacetate, sodium meta-phosphate, succinic acid, urea, cyclodextrin, polyvinylpyrrolidone, diethylammonium-ortho-benzoate, and micelle- forming solubilizers such as TWEENS and spans, e.g., TWEEN 80. Other solubilizers that are usable for the compositions of the present invention are, for example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene n-alkyl ethers, n-alkyl amine n-oxides, poloxamers, organic solvents, phospholipids and cyclodextrines.

Suitable penetration enhancers include, but are not limited to, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), allantoin, urazole, N,N-dimethylacetamide (DMA), decylmethylsulfoxide (Cio MSO), polyethylene glycol monolaurate (PEGML), propyleneglycol (PG), propyleneglycol monolaurate (PGML), glycerol monolaurate (GML), lecithin, the 1 -substituted azacycloheptan-2-ones, particularly 1-n- dodecylcyclazacycloheptan-2-one (available under the trademark Azone^® from Whitby Research Incorporated, Richmond, Va.), alcohols, and the like. The permeation enhancer may also be a vegetable oil. Such oils include, for example, safflower oil, cottonseed oil and corn oil.

Suitable anti-irritants include, for example, steroidal and non steroidal antiinflammatory agents or other materials such as aloe vera, chamomile, alpha-bisabolol, cola nitida extract, green tea extract, tea tree oil, licoric extract, allantoin, caffeine or other xanthines, glycyrrhizic acid and its derivatives.

Exemplary additional active agents according to these embodiments of present invention include, without limitation, one or more, or any combination of an antibiotic agent, an antimicrobial agent, an anti-acne agent, an anti-aging agent, a wrinkle- reducing agent, a skin whitening agent, a sebum reducing agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a nonsteroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, an antineoplastic agent, an immunomodulator, an interferon, an antidepressant, an anti histamine, a vitamin, a hormone and an anti- dandruff agent.

In some of any of the embodiments described herein, a topical formulation comprises, in addition to the microcapsules encapsulating a silicone material as described herein, an additional agent, as described herein, which is encapsulated. In some of these embodiments, the topical formulation comprises an additional type of microcapsules, which encapsulate the additional agent.

Exemplary such microcapsules are microcapsules as described in U.S. Patent

Nos. 6,932,984 and 7,838,037 and WO 2012/156965. More specific examples include microcapsules marketed by Tagra, under the tradenames TagraCapl™, TagraCap3™ and CameleonCaps™, for colorant-encapsulating microcapsules; SunCaps™, for UV filter-encasulating microcapsules; Tagravit™ for vitamin-encapsulating microcapsules; and Tagrol™, for essential oil-encapsulating microcapsules.

In some of any of the embodiments described herein, the topical formulation is an aqueous-based formulation, including aqueous-containing emulsions.

In some of any of the embodiments described herein, the formulation comprises a surfactant in an amount lower than 2 %, or lower than 1 %, or lower than 0.5 %, or lower than 0.1 %, or lower than 0.05 %, or lower than 0.01 %, or even lower %, by weight, of the total weight of the formulation.

In some of any of the embodiments described herein, the formulation comprises a surfactant in an amount that is lower by 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90 %, 100 %, 150 %, 200 % and more, compared to the same formulation in which the same amount of the same silicone material is not encapsulated.

In some of any of the embodiments described herein, the formulation is devoid of a surfactant.

By "devoid of in the context of these embodiments, it is meant less than 0.01% or less than 0.001%, or less than 0.0001%, by weight, of the total weight of the formulation, or null.

In some of any of the embodiments described herein, the viscosity of a topical formulation as described herein is substantially the same as the viscosity of the same formulation without the silicone-containing microcapsules as described herein.

By "substantially the same" it is meant + 20 %, or + 15 %, or + 10 %, or + 5 %, or + 2 %, or + 1 %, including any other intermediate value between + 0.1-20 %.

In some of any of the embodiments described herein, the viscosity of a topical formulation as described herein is lower by 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90 %, 100 %, 150 %, 200 % and more, compared to the same formulation in which the same amount of the same silicone material is not encapsulated.

In some embodiments, the topical formulation comprises an active agent or another silicone material which is otherwise incompatible with the encapsulated silicone material.

According to an aspect of some embodiments of the present invention there are provided articles-of-manufacturing (or products) comprising a microcapsule, a composition, and/or a topical formulation, as described herein in any of the respective embodiments. Exemplary such articles include, but are not limited to, skin care products, men's grooming products, suncare products, products in a form of pressed powders, and color cosmetic products (e.g., eye shadows, lipsticks, etc.).

Thus, the topical formulations, products and article-of-manufacturing described herein allows incorporation of silicone materials at higher concentrations, without substantially affecting the viscosity thereof, while reducing or even circumventing the amount of a surfactant, and while allowing co-formulation of other agents which are otherwise incompatible with the silicone material.

It is expected that during the life of a patent maturing from this application many relevant silicone materials will be developed and the scope of the term "silicone material" is intended to include all such new technologies a priori.

As used herein the term "about" refers to ± 10 % or ± 5 %.

The terms "comprises", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to".

The term "consisting of means "including and limited to".

The term "consisting essentially of" means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof.

Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases "ranging/ranges between" a first indicate number and a second indicate number and "ranging/ranges from" a first indicate number "to" a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

As used herein the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

hydrogen, alkyl, alkoxy, hydroxy, alkenyl, vinyl, alkaryl, aryl, alkylene glycol, poly(alkylene glycol), heteroaryl, carboxy, thiocarboxy, a silane, a siloxane, and the like, or, alternatively, A and B are linked together to form a cyclic polysiloxane (cyclomethicone); and

Ri and R₂ are each independently a pendant group, which can be, for example, hydrogen, alkyl, alkoxy, hydroxy, alkenyl, vinyl, alkaryl, aryl, alkylene glycol, poly(alkylene glycol), heteroaryl, carboxy, thiocarboxy,

The term "alkyl" describes a saturated aliphatic hydrocarbon including straight chain and branched chain groups. Preferably, the alkyl group has 1 to 20 carbon atoms. Whenever a numerical range; e.g. , " 1-20", is stated herein, it implies that the group, in this case the alkyl group, may contain 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms. More preferably, the alkyl is a medium size alkyl having 1 to 10 carbon atoms. Most preferably, unless otherwise indicated, the alkyl is a lower alkyl having 1 to 4 carbon atoms (C(l-4) alkyl). The alkyl group may be substituted or unsubstituted. Substituted alkyl may have one or more substituents, whereby each substituent group can independently be, for example, hydroxyalkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, amine, halide, sulfonate, sulfoxide, phosphonate, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, azo, sulfonamide, C-carboxylate, O-carboxylate, N-thiocarbamate, O-thiocarbamate, urea, thiourea, N-carbamate, O-carbamate, C- amide, N-amide, guanyl, guanidine and hydrazine.

When an alkyl group connects two or more moieties via at least two carbons in its chain, it is also referred to herein as "alkylene" or "alkylene chain".

Alkene and Alkyne, as used herein, are an alkyl, as defined herein, which contains one or more double bond or triple bond, respectively.

The term "vinyl" describes an alkyl (e.g., methylene) terminated by an alkene group.

The term "alkaryl" described an alkyl (e.g., methylene) substituted by an aryl, group, as described herein. An example is benzyl.

The term "cycloalkyl" describes an all-carbon monocyclic ring or fused rings (i.e., rings which share an adjacent pair of carbon atoms) group where one or more of the rings does not have a completely conjugated pi-electron system. Examples include, without limitation, cyclohexane, adamantine, norbornyl, isobornyl, and the like. The cycloalkyl group may be substituted or unsubstituted. Substituted cycloalkyl may have one or more substituents, whereby each substituent group can independently be, for example, hydroxyalkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, amine, halide, sulfonate, sulfoxide, phosphonate, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, azo, sulfonamide, C- carboxylate, O-carboxylate, N-thiocarbamate, O-thiocarbamate, urea, thiourea, N-carbamate, O-carbamate, C-amide, N-amide, guanyl, guanidine and hydrazine.

The term "heteroalicyclic" describes a monocyclic or fused ring group having in the ring(s) one or more atoms such as nitrogen, oxygen and sulfur. The rings may also have one or more double bonds. However, the rings do not have a completely conjugated pi-electron system. Representative examples are piperidine, piperazine, tetrahydrofuran, tetrahydropyrane, morpholino, oxalidine, and the like. The heteroalicyclic may be substituted or unsubstituted. Substituted heteroalicyclic may have one or more substituents, whereby each substituent group can independently be, for example, hydroxyalkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, amine, halide, sulfonate, sulfoxide, phosphonate, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, azo, sulfonamide, C- carboxylate, O-carboxylate, N-thiocarbamate, O-thiocarbamate, urea, thiourea, O- carbamate, N-carbamate, C-amide, N-amide, guanyl, guanidine and hydrazine.

The term "aryl" describes an all-carbon monocyclic or fused-ring polycyclic

(i.e., rings which share adjacent pairs of carbon atoms) groups having a completely conjugated pi-electron system. The aryl group may be substituted or unsubstituted. Substituted aryl may have one or more substituents, whereby each substituent group can independently be, for example, hydroxyalkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, amine, halide, sulfonate, sulfoxide, phosphonate, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, azo, sulfonamide, C-carboxylate, O-carboxylate, N-thiocarbamate, O-thiocarbamate, urea, thiourea, N-carbamate, O-carbamate, C-amide, N-amide, guanyl, guanidine and hydrazine.

The term "heteroaryl" describes a monocyclic or fused ring (i.e., rings which share an adjacent pair of atoms) group having in the ring(s) one or more atoms, such as, for example, nitrogen, oxygen and sulfur and, in addition, having a completely conjugated pi-electron system. Examples, without limitation, of heteroaryl groups include pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrimidine, quinoline, isoquinoline and purine. The heteroaryl group may be substituted or unsubstituted. Substituted heteroaryl may have one or more substituents, whereby each substituent group can independently be, for example, hydroxyalkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, amine, halide, sulfonate, sulfoxide, phosphonate, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, azo, sulfonamide, C-carboxylate, O-carboxylate, N-thiocarbamate, O-thiocarbamate, urea, thiourea, O-carbamate, N-carbamate, C-amide, N-amide, guanyl, guanidine and hydrazine. Representative examples are pyridine, pyrrole, oxazole, indole, purine and the like.

As used herein, the term "amine" describes both a -NR'R" group and a -NR'- group, wherein R' and R" are each independently hydrogen, alkyl, cycloalkyl, aryl, as these terms are defined hereinbelow.

The amine group can therefore be a primary amine, where both R' and R" are hydrogen, a secondary amine, where R' is hydrogen and R" is alkyl, cycloalkyl or aryl, or a tertiary amine, where each of R' and R" is independently alkyl, cycloalkyl or aryl.

Alternatively, R' and R" can each independently be hydroxyalkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, amine, halide, sulfonate, sulfoxide, phosphonate, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, azo, sulfonamide, carbonyl, C-carboxylate, O-carboxylate, N-thiocarbamate, O-thiocarbamate, urea, thiourea, N-carbamate, O-carbamate, C- amide, N-amide, guanyl, guanidine and hydrazine.

The term "halide" and "halo" describes fluorine, chlorine, bromine or iodine.

The term "haloalkyl" describes an alkyl group as defined above, further substituted by one or more halide.

The term "sulfate" describes a -0-S(=0)₂-OR' group, or an -0-S(=0)₂-0- group, where R' is as defined hereinabove.

The term "thiosulfate" describes a -0-S(=S)(=0)-OR' group or a -O-

S(=S)(=0)-0-group, where R' is as defined hereinabove.

The term "sulfite" describes an -0-S(=0)-0-R' group or a -0-S(=0)-0-group, where R' is as defined hereinabove.

The term "thiosulfite" describes a -0-S(=S)-0-R' group or an -0-S(=S)-0- group, where R' is as defined hereinabove.

The term "sulfinate" describes a -S(=0)-OR' group or an -S(=0)-0- group, where R' is as defined hereinabove.

The term "sulfoxide" or "sulfinyl" describes a -S(=0)R' group or an -S(=0)- group, where R' is as defined hereinabove.

The term "sulfonate" describes a -S(=0)₂-R' group or an -S(=0)₂- group, where

R' is as defined herein. The term "S-sulfonamide" describes a -S(=0)2-NR'R" group or a -S(=0)₂- NR'-group, with R' and R' ' as defined herein.

The term "N-sulfonamide" describes an R'S(=0)₂-NR"- group or a -S(=0)₂-NR'-group, where R' and R" are as defined herein.

The term "sulfone" describes a -S-R'R" group or -SR'- group, where R' and

R" are as defined herein.

The term "phosphonate" describes a -P(=0)(OR')(OR") group or a -P(=0)(OR')(0)- group, with R' and R" as defined herein.

The term "thiophosphonate" describes a -P(=S)(OR')(OR") group or a -P(=S)(OR')(0)- group, with R' and R" as defined herein.

The term "phosphinyl" or "phosphine" describes a -PR'R" group or a -PR'- group, with R' and R" as defined hereinabove.

The term "phosphine oxide" describes a -P(=0)(R')(R") group or a -P(=0)(R')- group, with R' and R" as defined herein.

The term "phosphine sulfide" describes a -P(=S)(R')(R") group or a -P(=S)(R')- group, with R' and R" as defined herein.

The term "phosphate" describes an -0-PR'(=0)(OR") group or an -O- PR'(=0)(0)- group, with R' and R" as defined herein.

The term "phosphonate" describes a -PR'(=0)(OR") group or a PR'(=0)(0)- group, with R' and R" as defined herein.

The term "carbonyl" or "carbonate" as used herein, describes a -C(=0)-R' group or a -C(=0)- group, with R' as defined herein.

The term "thiocarbonyl " as used herein, describes a -C(=S)-R' group or a - C(=S)- group, with R' as defined herein.

The term "oxo" as used herein, describes a (=0) group, wherein an oxygen atom is linked by a double bond to the atom (e.g., carbon atom) at the indicated position.

The term "thiooxo" as used herein, describes a (=S) group, wherein a sulfur atom is linked by a double bond to the atom (e.g., carbon atom) at the indicated position.

The term "oxime" describes a =N-OH group or a =N-0- group.

The term "hydroxyl" describes a -OH group. The term "alkoxy" describes both an -O-alkyl and an -O-cycloalkyl group, as defined herein.

The term "aryloxy" describes both an -O-aryl and an -O-heteroaryl group, as defined herein.

The term "thiohydroxy" describes a -SH group.

The term "thioalkoxy" describes both a -S-alkyl group, and a -S-cycloalkyl group, as defined herein.

The term "thioaryloxy" describes both a -S-aryl and a -S-heteroaryl group, as defined herein.

The "hydroxyalkyl" is also referred to herein as "alcohol", and describes an alkyl, as defined herein, substituted by a hydroxy group.

The term "cyano" describes a -C≡N group.

The term "isocyanate" describes an -N=C=0 group.

The term "isothiocyanate" describes an -N=C=S group.

The term "nitro" describes an -N0₂ group.

The term "acyl halide" describes a -(C=0)R"" group wherein R"" is halide, as defined hereinabove.

The term "carboxylate" as used herein encompasses C-carboxylate and O- carboxylate.

The term "C-carboxylate" describes a -C(=0)-OR' group or a -C(=0)-0- group, where R' is as defined herein.

The term "O-carboxylate" describes a -OC(=0)R' group or a -OC(=0)- group, where R' is as defined herein. When R' is other than H, this term describes an ester.

A carboxylate can be linear or cyclic. When cyclic, R' and the carbon atom are linked together to form a ring, in C-carboxylate, and this group is also referred to as lactone. Alternatively, R' and O are linked together to form a ring in O-carboxylate. Cyclic carboxylates can function as a linking group, for example, when an atom in the formed ring is linked to another group.

The term "thiocarboxylate" as used herein encompasses C-thiocarboxylate and O-thiocarboxylate.

The term "C-thiocarboxylate" describes a -C(=S)-OR' group or a -C(=S)-0- group, where R' is as defined herein. The term "O-thiocarboxylate" describes a -OC(=S)R' group or a -OC(=S)- group, where R' is as defined herein.

A thiocarboxylate can be linear or cyclic. When cyclic, R' and the carbon atom are linked together to form a ring, in C-thiocarboxylate, and this group is also referred to as thiolactone. Alternatively, R' and O are linked together to form a ring in O- thiocarboxylate. Cyclic thiocarboxylates can function as a linking group, for example, when an atom in the formed ring is linked to another group.

The term "carbamate" as used herein encompasses N-carbamate and O- carbamate.

The term "N-carbamate" describes an R"OC(=0)-NR'- group or a -OC(=0)-

NR'- group, with R' and R" as defined herein.

The term "O-carbamate" describes an -OC(=0)-NR'R" group or an -OC(=0)- NR'- group, with R' and R" as defined herein.

A carbamate can be linear or cyclic. When cyclic, R' and the carbon atom are linked together to form a ring, in O-carbamate. Alternatively, R' and O are linked together to form a ring in N-carbamate. Cyclic carbamates can function as a linking group, for example, when an atom in the formed ring is linked to another group.

The term "carbamate" as used herein encompasses N-carbamate and O- carbamate.

The term "thiocarbamate" as used herein encompasses N-thiocarbamate and O- thiocarbamate.

The term "O-thiocarbamate" describes a -OC(=S)-NR'R" group or a -OC(=S)-NR'- group, with R' and R" as defined herein.

The term "N-thiocarbamate" describes an R"OC(=S)NR'- group or a -OC(=S)NR'- group, with R' and R" as defined herein.

Thiocarbamates can be linear or cyclic, as described herein for carbamates.

The term "dithiocarbamate" as used herein encompasses S-dithiocarbamate and N-dithiocarbamate.

The term "S-dithiocarbamate" describes a -SC(=S)-NR'R" group or a -SC(=S)NR'- group, with R' and R" as defined herein.

The term "N-dithiocarbamate" describes an R"SC(=S)NR'- group or a -SC(=S)NR'- group, with R' and R" as defined herein. The term "urea", which is also referred to herein as "ureido", describes a -NR'C(=0)-NR"R" ' group or a -NR'C(=0)-NR"- group, where R' and R" are as defined herein and R'" is as defined herein for R' and R".

The term "thiourea", which is also referred to herein as "thioureido", describes a -NR'-C(=S)-NR"R" ' group or a -NR'-C(=S)-NR"- group, with R', R" and R' " as defined herein.

The term "amide" as used herein encompasses C-amide and N-amide.

The term "C-amide" describes a -C(=0)-NR'R" group or a -C(=0)-NR'- group, where R' and R" are as defined herein.

The term "N-amide" describes a R'C(=0)-NR"- group or a R'C(=0)-N- group, where R' and R" are as defined herein.

An amide can be linear or cyclic. When cyclic, R' and the carbon atom are linked together to form a ring, in C-amide, and this group is also referred to as lactam. Cyclic amides can function as a linking group, for example, when an atom in the formed ring is linked to another group.

The term "guanyl" describes a R'R"NC(=N)- group or a -R'NC(=N)- group, where R' and R" are as defined herein.

The term "guanidine" describes a -R'NC(=N)-NR"R" ' group or a -R'NC(=N)- NR"- group, where R', R" and R'" are as defined herein.

The term "hydrazine" describes a -NR'-NR"R" ' group or a -NR'-NR"- group, with R', R", and R'" as defined herein.

As used herein, the term "hydrazide" describes a -C(=0)-NR'-NR"R"' group or a -C(=0)-NR'-NR"- group, where R', R" and R'" are as defined herein.

As used herein, the term "thiohydrazide" describes a -C(=S)-NR'-NR"R"' group or a -C(=S)-NR'-NR"- group, where R', R" and R'" are as defined herein.

As used herein, the term "alkylene glycol" describes a -0-[(CR'R")x-0]y-R' " end group or a -0-[(CR'R")_z-0]_y- linking group, with R', R" and R" ' being as defined herein, and with z being an integer of from 1 to 10, preferably, 2-6, more preferably 2 or 3, and y being an integer of 1 or more. Preferably R' and R" are both hydrogen. When z is 2 and y is 1, this group is ethylene glycol. When z is 3 and y is 1, this group is propylene glycol. When y is greater than 4, the alkylene glycol is referred to herein as poly(alkylene glycol). In some embodiments of the present invention, a poly(alkylene glycol) group or moiety can have from 10 to 200 repeating alkyelene glycol units, such that z is 10 to 200, preferably 10-100, more preferably 10-50.

The term "silane" describes a -Si-R'R"R"' group, with R', R" and R'" as described herein.

The term "siloxane" describes a -Si(OR')R"R" ' or -Si(OR')(OR")R" ', or - Si(OR')(ORR")(OR" '), with R', R" and R' " as described herein.

Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.

EXAMPLES

Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non-limiting fashion.

EXAMPLE 1

Preparation of microcapsules containing Dimethicone with lOOcst viscosity

/./ Preparation of organic phase/master batch (MB) stage

An organic phase (herein referred to interchangeably as "master batch" (MB)) was prepared by gradually adding 11 grams of the wall-forming polymer Cellulose Acetate Propionate (CAP), under stirring, into 249.6 grams of ethyl acetate until the mixture was homogeneous and transparent (about 10 minutes). In a separate vessel, 89 grams of Dimethicone with lOOcst viscosity was added into 107 grams of methyl acetate and mixed until the mixture was homogeneous and transparent (about 10 minutes), and the mixture was thereafter poured gradually to the polymer/ethyl acetate mixture during continuous mixing. The components of the MB are presented in Table 1. Master batch constituents

1.2 Preparation of the emulsion

An aqueous solution of 0.5 % polyvinyl alcohol (PVA) was prepared by mixing water (589.8 grams) with PVA 4 % solution (84.3 grams). Ethyl acetate (74.9 grams) was added to the water phase, and then the master batch of step 1.1 above was gradually added into the ethyl acetate/water emulsion under stirring at about 300 RPM for 5 minutes. The ratio between the master batch and the emulsion (w/w) was 1:3. The components of the emulsion are presented in Table 2.

Table 2. Emulsion constituents

1.3 Extraction of the organic solvent

The extraction fluid was composed of a mixture of 7025.7 grams water and 88.9 grams of PVA solution 4 % (final concentration of PVA in the extraction fluid 0.05 % PVA). The emulsion of step 1.2 above (1205.5 grams) was gradually added into the extraction fluid in a 10 L pail under stirring at 150 RPM using a manual pump, and was further stirred for additional 15 minutes. The resulting mixture was left for about 24 hours at 25 °C. The components of the extraction medium are presented in Table 3.

Table 3. Extraction medium constituents

1.4 Washing, Drying and Sifting of the microcapsules

The microcapsules obtained in step 1.3 above were separated by vacuum filtration. The upper phase, containing the microcapsules, was harvested, filtered, and washed with 500 ml water. The suspension was transferred to a drying vessel. In the drying stage, the microcapsules were freeze dried (lyophilized) for 48 hours.

The microcapsules were stored in an appropriate container in room temperature or at a refrigerator.

EXAMPLE 2

Preparation of microcapsules containing Dimethicone with 350cst viscosity

2.1 Preparation of organic phase/master batch (MB) stage

An organic phase (herein referred to interchangeably as "master batch" (MB)) was prepared by gradually adding the wall-forming polymers: 6.5 grams of Cellulose Acetate Propionate (CAP) and 6.5 grams of poly (methyl methacrylate) (PMMA) under stirring, into 249.6 grams of ethyl acetate, heating to 50 °C and stirring well until the mixture was homogeneous and transparent (about 20 minutes). The obtained polymer solution was cooled to 25 °C.

In separate vessel, 85.9 grams of Dimethicone with 350cst viscosity was added into 107 grams of methyl acetate and mixed until the mixture was homogeneous and transparent (about 10 minutes), and the mixture was thereafter gradually poured to the polymers/ethyl acetate mixture during continuous mixing. Then, Magnesium Stearate (MgSt) was added and the obtained mixture was homogenized for about 6 minutes. The components of the MB are presented in Table 4.

Table 4. Master batch constituents

2.2 Preparation of the emulsion

An aqueous solution of 0.5 % polyvinyl alcohol (PVA) was prepared by mixing water (589.8 grams) with PVA 4 % solution (84.3 grams). Ethyl acetate (74.9 grams) was added to the water phase, and then the master batch of step 2.1 above was gradually added into the ethyl acetate/water emulsion under stirring at about 300 RPM for 5 minutes. The ratio between the master batch and the emulsion (w/w) was 1:3. The components of the emulsion are presented in Table 5.

Table 5. Emulsion constituents

Material Loading (grams)

1 Water 589.8

PVA (Mowiol 4-88, KSE solution 4 %;

2 84.3

Kuraray America, Inc., USA)

3 Ethyl Acetate (Sciencelab.com, Inc., USA) 74.9

4 MB 456.6 2.3 Extraction of the organic solvent

The extraction fluid was composed of a mixture of 7025.7 grams water and 88.9 grams of PVA solution 4 % (final concentration of PVA in the extraction fluid 0.05 % PVA). The emulsion of step 2.2 above (1205.5 grams) was gradually added into the extraction fluid in a 10 L pail under stirring at 150 RPM using a manual pump, and was further stirred for additional 15 minutes. The resulting mixture was left for about 24 hours at 25 °C. The components of the extraction medium are presented in Table 6.

Table 6. Extraction medium constituents

1.4 Washing, Drying and Sifting of the microcapsules

The microcapsules obtained in step 2.3 above were separated by vacuum filtration. The upper phase, containing the microcapsules, was harvested, filtered, and washed with 500 ml water. The suspension was transferred to a drying vessel. In the drying stage, the microcapsules were freeze dried (lyophilized) for 48 hours.

EXAMPLE 3

Preparation of microcapsules containing Dimethicone with 1503cst viscosity 3.1 Preparation of organic phase/master batch (MB) stage

An organic phase (herein referred to interchangeably as "master batch" (MB)) was prepared by gradually adding 11 grams of the wall-forming polymer Cellulose Acetate Propionate (CAP) under stirring, into 249.6 grams of ethyl acetate until the mixture was homogeneous and transparent (about 10 minutes). Then, Propylene glycol monopalmitostearate was added and mixing continued until the mixture was homogeneous and transparent (about 10 minutes). In a separate vessel, 89 grams of Dimethicone with 1503cst viscosity was added into 107 grams of methyl acetate and mixed until the mixture was homogeneous and transparent (about 10 minutes), and the mixture was thereafter gradually poured to the polymer/ethyl acetate mixture during continuous mixing. The components of the MB are presented in Table 7.

Table 7. Master batch constituents

3.2 Preparation of the emulsion

An aqueous solution of 0.5 % polyvinyl alcohol (PVA) was prepared by mixing water (589.8 grams) with PVA 4 % solution (84.3 grams). Ethyl acetate (74.9 grams) was added to the water phase, and then the master batch of step 3.1 above was gradually added into the ethyl acetate/water emulsion under stirring at about 300 RPM for 5 minutes. The ratio between the master batch and the emulsion (w/w) was 1:3. The components of the emulsion are presented in Table 8.

Table 8. Emulsion constituents

3.3 Extraction of the organic solvent

The extraction fluid was composed of a mixture of 7025.7 grams water and 88.9 grams of PVA solution 4 % (final concentration of PVA in the extraction fluid 0.05 % PVA). The emulsion of step 3.2 above (1205.5 grams) was gradually added into the extraction fluid in a 10 L pail under stirring at 150 RPM using a manual pump, and was further stirred for additional 15 minutes. The resulting mixture was left for about 24 hours at 25 °C. The components of the extraction medium are presented in Table 9.

Table 9. Extraction medium constituents

3.4 Washing, Drying and Sifting of the microcapsules

The microcapsules obtained in step 3.3 above were separated by vacuum filtration. The upper phase, containing the microcapsules, was harvested, filtered, and washed with 500 ml water. The suspension was transferred to a drying vessel. In the drying stage, the microcapsules were freeze dried (lyophilized) for 48 hours.

The microcapsules were stored in an appropriate container in room temperature or at a refrigerator. EXAMPLE 4

Preparation of microcapsules containing Dimethicone with 1503cst viscosity and silicone elastomer

4.1 Preparation of organic phase/master batch (MB) stage

An organic phase (herein referred to interchangeably as "master batch" (MB)) was prepared by gradually adding 11 grams of the wall-forming polymer Cellulose Acetate Propionate (CAP), under stirring, into 249.6 grams of ethyl acetate until the mixture was homogeneous and transparent (about 10 minutes). In a separate vessel, 32.6 grams of Dimethicone with 1503cst viscosity was added into 107 grams of methyl acetate until the mixture was homogeneous and transparent (about 10 minutes), and the mixture was thereafter gradually poured into the polymer/ethyl acetate mixture, during continuous mixing. Then, 56.4 grams of a silicone elastomer (see, Table 10, entry 3) were added and the obtained mixture was homogenized for about 6 minutes. The components of the MB are presented in Table 10.

Table 10. Master batch constituents

4.2 Preparation of the emulsion

An aqueous solution of 0.5 % polyvinyl alcohol (PVA) was prepared by mixing water (589.8 grams) with PVA 4 % solution (84.3 grams). Ethyl acetate (74.9 grams) was added to the water phase, and then the master batch of step 4.1 above was gradually added into the ethyl acetate/water emulsion under stirring at about 300 RPM for 5 minutes. The ratio between the master batch and the emulsion (w/w) was 1:3. The components of the emulsion are presented in Table 11.

Table 11. Emulsion constituents

4.3 Extraction of the organic solvent

The extraction fluid was composed of a mixture of 7025.7 grams water and 88.9 grams of PVA solution 4 % (final concentration of PVA in the extraction fluid 0.05 % PVA). The emulsion of step 4.2 above (1205.5 grams) was gradually added into the extraction fluid in a 10 L pail under stirring at 150 RPM using a manual pump, and was further stirred for additional 15 minutes. The resulting mixture was left for about 24 hours at 25 °C. The components of the extraction medium are presented in Table 12.

Table 12. Extraction medium constituents

4.4 Washing, Drying and Sifting of the microcapsules

The microcapsules obtained in step 4.3 above were separated by vacuum filtration. The upper phase, containing the microcapsules, was harvested, filtered, and washed with 500 ml water. The suspension was transferred to a drying vessel. In the drying stage, the microcapsules were freeze dried (lyophilized) for 48 hours. The microcapsules were stored in an appropriate container in room temperature or at a refrigerator.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

Claims

WHAT IS CLAIMED IS:

1. A microcapsule comprising an inner core enveloped by an outer shell formed of a wall-forming polymeric material, said inner core comprising a silicone material.

2. The microcapsule of claim 1, wherein an amount of said inner core is at least 50 weight percents of the total weight of the microcapsule.

3. The microcapsule of claim 1 or 2, wherein an amount of said silicone material ranges from about 50 % to about 90 %, by weight, of the total weight of the microcapsule.

4. The microcapsule of any one of claims 1 to 3, wherein an amount of said silicone material ranges from about 70 % to about 90 %, or from about 80 % to about 90 %, by weight, of the total weight of the microcapsule.

5. The microcapsule of any one of claims 1 to 4, wherein said inner core consists of said silicone material.

6. The microcapsule of any one of claims 1 to 5, wherein said silicone material is selected from the group consisting of a silicone oil (e.g., a dimethicone, a phenyltrimethicone), and a silicone resin (e.g., a silicone elastomer) and any combination thereof.

7. The microcapsule of any one of claims 1 to 6, wherein said silicone material comprises a dimethicone.

8. The microcapsule of claim 7, wherein said dimethicone features a viscosity of from 50 to 5000 centipoises at room temperature.

9. The microcapsule of any one of claims 1 to 8, further comprising a fatty substance.

10. The microcapsule of claim 9, wherein said fatty substance is a fatty acid salt.

11. The microcapsule of claim 10, wherein said fatty acid is selected from the group consisting of stearic acid, arachidic acid, palmitoleic acid, oleic acid, linoleic acid, linolaidic acid, arachidonic acid, myristoleic acid and erucic acid.

12. The microcapsule of claim 9 or 11, wherein said fatty acid salt is selected from the group consisting of magnesium stearate, magnesium oleate, calcium stearate, calcium linoleate, and sodium stearate.

13. The microcapsule of claim 9, wherein said fatty substance is a glycolipid.

14. The microcapsule of claim 9 or 13, wherein said fatty substance is a propylene glycol stearate.

15. The microcapsule of any one of claims 10 to 14, wherein said fatty substance further comprises a fatty acid.

16. The microcapsule of any one of claims 9 to 13, wherein an amount of said fatty acid salt ranges from about 0.1 % to about 10 %, or from about 1 % to about 10 %, by weight, of the total weight of the microcapsule.

17. The microcapsule of any one of claims 1 to 16, wherein said wall- forming polymeric material comprises a polymer or copolymer selected from the group consisting of polyacrylate, a polymethacrylate, a cellulose ether, a cellulose ester, copolymers thereof and any combination thereof.

18. The microcapsule of claim 17, wherein said polymer or copolymer is selected from the group consisting of a polyacrylate, a polymethacrylate, an acrylate/ammonium methacrylate copolymer, an ammonium methacrylate copolymer type B, low molecular weight (about 15,000 Dalton) poly(methyl methacrylate)-co- (methacrylic acid), poly(ethyl acrylate)-co-(methyl methacrylate)-co-(trimethyl ammonium-ethyl methacrylate chloride), poly(butyl methacrylate)-co-(2-dimethy laminoethyl methacrylate )-co-(methyl methacrylate)), poly(styrene)-co-(maleic anhydride), copolymer of octylacrylamide, cellulose ether, cellulose ester, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), PLA (poly lactic acid), PGA (poly glycolic acid) and PLGA copolymer.

19. The microcapsule of claim 17, wherein said wall-forming material comprises a cellulose ester.

20. The microcapsule of claim 17, wherein said wall-forming material comprises cellulose acetate propionate.

21. The microcapsule of any one of claims 1 to 20, wherein an amount of said wall-forming polymeric material ranges from about 1 % to about 50 %, or from about 5 % to about 20 %, or from about 10 % to about 15 %, by weight, of the total weight of the microcapsule.

22. The microcapsule of any one of claims 1 to 21, further comprising a colorant and/or an opaque substance.

23. The microcapsule of claim 22, wherein said colorant is in said inner core.

24. The microcapsule of claim 22 or 23, wherein said colorant and/or said opaque substance are in said outer shell.

25. The microcapsule of any one of claims 1 to 24, further comprising an additional active agent.

26. The microcapsule of claim 25, wherein said additional active agent is in said inner core.

27. The microcapsule of any one of claims 1 to 26, further comprising a plasticizer.

28. The microcapsule of claim 27, wherein said plasticizer is selected from the group consisting of triethyl citrate, tricaprylin, trilaurin, tripalmitin, triacetin, acetyltriethyl citrate, paraffin oil, and any combination thereof.

29. The microcapsule of any one of claims 1 to 28, wherein said outer shell comprises:

said wall-forming polymeric material in an amount that ranges from about 5 % to about 20 %, by weight, of the total weight of the microcapsule; and

said fatty acid salt in an amount that ranges from about 0 to about 10 %, by weight, of the total weight of the microcapsule.

30. The microcapsule of claim 29, wherein:

said wall-forming polymeric material comprises a cellulose acetate;

said fatty acid salt is a salt of stearic acid; and

said inner core comprises dimethicone.

31. The microcapsule of any one of claims 1 to 30, being a single-layer microcapsule.

32. A composition comprising a plurality of microcapsules, at least a portion of said microcapsules comprising the microcapsules of any one of claims 1 to 31.

33. The composition of claim 32, wherein at least 50 %, or at least 80 %, or at least 90 % of the microcapsules are the microcapsules of any one of claims 1 to 31.

34. The composition according to claim 32 or 33, wherein substantially all of the microcapsules are microcapsules according to any one of claims 1 to 31.

35. The composition of any one of claims 32 to 34, wherein a mean size of said plurality of microcapsules ranges from about 1 μιη to about 1000 μιη, or from about 50 μιη to about 500 μιη, or from about 50 μιη to about 200 μιη, or from about 50 μιη to about 150 μιη, or is about 100 μιη.

36. The composition of any one of claims 32 to 35, being in a form of a powder or a paste.

37. A process of preparing the microcapsule according to any one of claims 1 to 31 or the composition according to any one of claims 32 to 36, the process comprising:

(a) contacting an organic phase comprising said silicone material, a wall- forming polymer or copolymer, optionally a fatty acid salt, and a partially water- miscible organic solvent with an aqueous continuous phase saturated with said organic solvent and comprising an emulsifier, to thereby obtain an emulsion; and

(b) contacting said emulsion with an extraction medium which comprises an amount of water which initiates extraction of said organic solvent from the emulsion, thereby obtaining the plurality of microcapsules.

38. The process of claim 37, further comprising isolating the microcapsules.

39. The process of claim 38, further comprising drying the microcapsules.

40. The process of any one of claims 37 to 39, wherein said organic solvent is selected from ethyl acetate, methyl acetate, ethanol, ethyl formate, and any combination thereof.

41. A microcapsule or a composition comprising a plurality of microcapsules, prepared by the process of any one of claims 37 to 40.

42. The microcapsule of any one of claims 1 to 31 and 41, being rupturable upon application of shear and/or mechanical force, thereby releasing said silicone material.

43. A formulation comprising the microcapsule of any one of claims 1 to 31 and 41 or the composition of any one of 35-39 and 41.

44. The formulation of claim 43, being for topical application.

45. The formulation of claim 43 or 44, further comprising a physiologically acceptable carrier.

46. The formulation according to claim 44 or 45, formulated as an oil-in- water emulsion, oil-in-water-in-oil emulsion, water-in-oil emulsion, a water-in-oil-in- water emulsion, an aqueous formulation, an anhydrous formulation, a silicon-based formulation and a powder formulation.

47. The formulation according to any one of claims 44 to 46, being an aqueous -containing formulation.

48. The formulation of any one of claims 44 to 47, being devoid of a surfactant.

49. The formulation according to any one of claims 44 to 46, being in the form of a gel, a powder, cream, foam, a stick, lotion, ointment, spray, oil, paste, milk, suspension, aerosol, or mousse.

50. An article-of-manufacturing comprising the microcapsule of any one of claims 1 to 31 and 41 or the composition of any one of claims 32 to 36 and 41.