MXPA05012215A

MXPA05012215A - Controlled release of active agents utilizing repeat sequence protein polymers

Info

Publication number: MXPA05012215A
Application number: MXPA/A/2005/012215A
Authority: MX
Inventors: Kumar Manoj; Mazeaud Isabelle; Patrick Christiano Steven
Original assignee: Patrick Christiano Steven; Kumar Manoj; Mazeaud Isabelle
Priority date: 2003-05-14
Filing date: 2005-11-11
Publication date: 2006-10-17

Abstract

Systems are provided for the controlled release delivery of active agents through the use of repeat sequence protein polymers. The systems may exist as matrices, gels, hydrogels, films, emulsions or microparticles and are particularly useful for incorporating active agents into personal care product compositions.

Description

CONTROLLED RELEASE OF ACTIVE AGENTS USING REPETITIVE SEQUENCE PROTEIN POLYMERS DESCRIPTION OF THE INVENTION The present invention relates to a system for providing the controlled release distribution of an active agent, and more particularly, to a system using repeating sequence protein polymers, to provide controlled release of active agents. In one aspect, the invention relates to personal care compositions that use repeating sequence protein polymers to provide controlled release of the active agents. Many active agents such as proteins, enzymes and vitamins have been used in personal care products to impart desired characteristics to the product. Sometimes it is desirable for the active agents to be distributed to hair, skin, nails and teeth in a controlled manner. Additionally, it is sometimes desirable that active agents such as enzymes remain in an active form in personal care products. However, many components of personal care products can inactivate active agents. The proteins can be chemically modified or quaternized in order to make them more soluble for inclusion in REF: 167969 personal care products. However, even chemically modified proteins can have all the desired characteristics. Thus, there is a need in the art for proteins having the desired characteristics, and for proteins that can be included in personal care formulations without chemical modification. There is also a need in the art to provide the easy formulation of proteins in personal care products and in the distribution to the skin or hair. In addition, there is a need in the art for methods and formulations to provide controlled release of active agents in personal care products. Accordingly, the present invention relates to systems that provide controlled release of the active agents through the use of repeating sequence protein polymers. Repetitive sequence protein polymers can be used to form complexes, complexes can also be processed to provide systems, for example, matrices, emulsions, gels, films, and microparticles. In specific embodiments, the engineered, recombinant forms of the repeating sequence protein polymers are employed. Repetitive sequence protein polymers generally comprise repetitive sequences of natural origin such as those found in silk or elastin. Protein polymers; Repetitive sequence can provide controlled release properties, with specific modalities, which provide triggered controlled release of an active agent. Other embodiments are directed to personal care product compositions comprising systems that provide controlled release, with additional modalities directed to the processes for making personal care product compositions. The processes comprise combining a system to provide the controlled release distribution of an active agent with a physiologically acceptable carrier or excipient to obtain a personal care composition. Alternatively, repeating sequence protein polymers, including recombinant forms, may be used in conjunction with at least one active agent to form microparticles by interfacial polymerization, and a complex is generally not formed. According to yet another aspect of this invention, methods are provided that increase the distribution of repetitive sequence protein polymers in personal care compositions. These methods comprise the formation of highly stable silicone complexes - protein polymer repetitive sequence, and the addition of complexes to personal care compositions. A further embodiment is directed to the repetitive sequence protein-silicone complexes, wherein at least one repetitive sequence protein polymer comprises a silk-like / elastin-like protein engineered. The more specific embodiments of the present invention provide silicone emulsions comprising complexes that provide particular benefits when employed in personal care composition products. The embodiments of the present invention use repeating, recombinant protein sequence polymers containing repeat units to provide, for example, controlled release of the active agents for personal care products. For purposes of defining and describing the present invention, "repetitive sequence protein polymer" (RSPP) refers to a polymer comprising repeated units of amino acid sequence, whose repeating units are derived from a natural or synthetic protein. For example, repetitive sequence units can be derived from natural, structural support materials such as silk, elastin and collagen. Alternatively, repetitive sequence units can be derived from synthetic structures. For purposes of defining and describing the present invention, "personal care composition" refers to a product for application to the skin, hair, nails, oral cavity and related membranes for purposes of improvement, cleaning, beautification, therapeutic treatment, and care for these surfaces and membranes. For purposes of defining and describing the present invention, an "effective amount" refers to the amount of the repeating sequence protein polymer that is added to a personal care composition, to provide the composition with a desired characteristic or characteristics. For purposes of defining and describing technology, the term "dispersed phase" is a well-known term for a person skilled in the art of emulsion technology, which means that the phase exists as small particles or droplets that are suspended in and surrounded by a continuous phase. The dispersed phase is also known as the continuous internal phase. For purposes of defining and describing the present invention, "active agent" will be understood as referring to a suitable product component including, but not limited to, silicones, fragrances, colorants, dyes, UV actives, sunscreens, lanolin, vitamins, bleaches, thickening agents, proteins, peptides, enzymes, antimicrobials and preservatives. For purposes of defining and describing the present invention, the term "protein" as used herein, shall be understood to comprise more than fifty (50) amino acids, while the term "peptide" as used herein, shall be understood to mean comprising 50 or less amino acids. In general, repeating sequence protein polymers can be used in a variety of ways to provide controlled release of the active agents. For example, the repeating sequence protein polymer can be used to form complexes with active agents, to act as a speed controlling polymer, and to serve as a component for microencapsulating active agents. The repeating units of the repeating sequence protein polymers of the present invention can be derived from natural structural support materials, such as silk, elastin and collagen. Alternatively, repetitive units can be derived from synthetic structures. Typically, repeating sequence protein polymers are synthesized and added to product formulations for conditioning hair or other hair products, skin products, products for personal care, or products for nail care, and the like. Protein polymers of recombinant repetitive sequence are comprised of repetitive units of natural or non-natural origin. There are more than six hundred repetitive protein sequences that are known to exist in biological systems at the time of submission of this application. The use of repetitive sequence protein polymers can provide hair care formulations with improved conditioning, treatment and repair properties. For example, well-known proteins containing repetitive protein sequences include abductin, elastin, bisus, flagelliform silks, trawl silk, the subunit of high molecular weight gluten (HMW), titin, fibromectin, leminin, and collagen. In addition, synthetic repetitive units can be used. Individual repeating units generally comprise from 3 to 30 amino acids, and will usually have the same amino acids that appear at least twice in the same unit. Typically, the individual units will comprise from about 3 to 8 amino acids. Therefore, each individual unit will typically be formed from about 3 to 8 amino acids. Different unit combinations may be joined together to form a block copolymer or an alternate block copolymer. Typically, the copolymers will have the following formula: Ty [(An) x (B) b (A / ".) X '(B') b '(A" n-.}. XvliT'y ... where T is an amino acid sequence of about 100 amino acids, usually from 1 to 60 amino acids, which can be any sequence, generally less than % of the total number of amino acids in the repeating protein copolymer; and is 0 or 1; T 'e and' are the same or different from T e and respectively, where the analogous symbols have the same definition as their counterparts; A is an individual unit of a repetitive amino acid sequence; n is an integer of at least 2 and not more than 250; x is 0 or an integer of at least 1, and will vary with the number of different amino acids in A to provide at least 30 amino acids in each repeating sequence A; A ', n' and x 'are the same as, or different from A, n and x respectively, being at least one different, where the analogous symbols have the same definition as their counterparts; A ", n" and x "are the same as, or different from A, n and x respectively, being at least one different, where the analogous symbols have the same definition as their counterparts, B is any amino acid sequence from 4 to 50 amino acids which is usually a functional sequence that results in a biological or chemical function or activity, b is 0 to 3, B 'and b' are the same as or different from B and b respectively, where the analogous symbols have the same definition as its counterparts, and i is 1 to 100, usually 1 to 50, more usually 1 to 30. In addition, the protein polymer can have the amino acid sequences that link the repeating units A, A 'and A "or the amino acid sequences that are link between the individual units A, A 'or A. These link sequences are typically from 1 to 10 amino acids and serve to link the repetitive units.These repetitive polymers can be synthesized by general methods. recognized chemical synthesis (eg, L. Anderson et al., Large-scale synthesis of peeptides, Biopolymers 55 (3), 227-50 (2000)), genetic manipulation (eg, J. Cappello, Genetically Engineered Protein Polymers , Handbook of Biodegradable Polymers, Domb, AJ; Post, J.; iseman, D (Eds.), Harvard Academic Publishers, Amsterdam; pages 387-414), and enzymatic synthesis (eg, C.H. ong &K.T. ang, New Developments in Enzymatic Peptide Synthesis, Experientia 47 (11-12), 1123-9 (1991)). For example, the repeating sequence protein polymers of the present invention can be synthesized using the methods described in U.S. Patent Nos. 5,243,038 and 6,355,776, the descriptions of which are incorporated by reference herein. In yet another example, repeating sequence protein polymers can be synthesized using the non-ribosomal peptide synthase (eg, HV Dohren et al., Multifunctional Peptide Synthase, Chem. Rev. 97, 2675-2705 (1997). of repetitive sequence can be produced on a commercial scale The units of the repetitive, individual amino acid sequence of particular interest include units found in silk-like proteins, elastin, collagen, abductin, biso, gluten, titin, extensin and fibronectin The silk-like proteins have a repetitive unit of SGAGAG (G = glycine; A = alanine; S = serine) (SEQ ID No. 1). found in the silk fibroin protein of natural origin, which can be represented as GAGAG (SGAGAG) sSGAAGY (Y = tyrosine) (SEQ ID No. 2). Elastin-like proteins have a repeating unit of GVGVP ( V = valine; P = proline) SEQ ID No. 3). This repetitive unit can be found in elastin of natural origin. Collagen-like proteins have repeating units of G-x-y (x = any amino acid, often alanine or proline, and = any amino acid, often proline or hydroxy proline). The abductin-like proteins have a repeating base unit of GGFGGMGGGx (F phenylalanine, M = methionine, x = any amino acid) (SEQ ID No. 4). The byssus-like proteins have a repeating unit of (GPGGG) (SEQ ID No. 5). Gluten-like proteins of the high molecular weight subunit have repeating units of PGQGQQ (SEQ ID No. 6); GYYPTSPQQ (SEQ ID No. 7), and GQQ (Q = glutamine, Y = tyrosine, T = threonine) (SEQ ID No. 8). The titin-like proteins have repeating units of PPAKVPEVPKKPVPEEKVPVPVPKKPEA (K = Usina, E = glutamic acid) (SEQ ID No. 9), and are found in the heart, psoas and muscle soleus. Extensive-like proteins have repeating units of SPPPPSPKYVYR (SEQ ID No. 10). Fibronectin-like proteins have repeating units of RGDS (R = arginine; D = aspartic acid) (SEQ ID No. 11). Additional repetitive units of interest are found in gliadin, glue polypeptide, ice nucleation protein, keratin, mucin, RNA polymerase II, and resilin. Gliadin has a repetitive unit of PQQPY (SEQ ID No. 12). The glue polypeptide has a repeating PTTTK unit (SEQ ID No. 13). The ice nucleation protein has a repeating unit of AGYGSTGT (SEQ ID No. 14). Keratin has a repeating unit of YGGSSGGG (SEQ ID No. 15) or FGGGS (SEQ ID No. 16). Mucin has a repeating unit of TTTPDV (SEQ ID No. 17). RNA polymerase II has a repeating unit of YSPTSPS (SEQ ID No. 18). In addition, resilin, the rubber-like protein, has repetitive units. It may be understood by those of ordinary skill in the art that the repeating sequence protein polymers of the present invention may be engineered to include appropriate repeating units in order to provide desired characteristics. For example, repeating sequence protein polymers can be produced to have wetting properties, to have a high glass transition temperature for hardness or strength, and / or to have a high cloudiness for heat sensitive applications. Similarly, proteins can be produced to have a high isoelectric point, to increase the affinity of the protein to hair, skin, and nails. Repetitive sequence protein polymers can be engineered to provide or enhance or design controlled release properties. For example, the molecular weight and composition of the protein can be chosen in order to increase or decrease the solubility in water, alter the diffusion coefficient, mechanical strength, biodegradation, or control the sensitivity to polymer stimuli. repeating sequence proteins, as desired to augment or design the controlled release properties of the repeating sequence protein polymer. Polymers use natural or synthetic repeating units, they can have their properties altered by the appropriate choice of different units, the number of units in each multimer, the spacing between the units, and the number of repetitions of the multimer. The multimer refers to the portion of the polymer represented by [(An) x (B) b (A'n.)? - (B ') b- (A "n«) x »] i, in the above formula. The spacing between the units refers to the other sequences represented by B or B 'in the above formula The preferred copolymers are combinations of silk units and elastin units to provide silk-elastin copolymers having distinctive properties of the polymers that they have only the same monomeric unit It can be understood by those skilled in the art that the repetitive sequence protein polymers of the present invention can be produced to have a combination of desirable characteristics, for example, a copolymer having repeating amounts Silk and repetitive units of elastin can be produced to impart durability due to repetitive silk units and impart flexibility due to the repetitive elastin units. In addition, the silk-elastin polymer can exhibit other desirable properties such as good clear film formation and hydrogel, which can not show the individual monomer units. The silk-elastin copolymer can be soluble in water. The silk-elastin copolymer can undergo irreversible gel-to-gel transition. For example, by increasing the temperature to between about 37 ° C to about 65 ° C or leaving the material at room temperature over time, the silk-elastin copolymer can undergo either an irreversible or reversible sol to gel transition, whereby water-insoluble films and hydrogels are formed. Films and water-insoluble hydrogels are desired for the controlled release of active ingredients and in personal care products, particularly for products applied to the skin, because they reduce the loss of water from the skin and increase the substantivity (they remain on the skin). The silk-elastin copolymer can also exhibit a high cloudiness, which is desirable in heat-sensitive applications. The silk-elastin copolymer can have a high isoelectric point, which can make the substantive copolymer to the skin and hair. The silk-elastin polymer can also show self-assembly into fibers and films, which may be desirable in some applications. It may further be understood by those of ordinary skill in the art that the repeating sequence protein polymers of the present invention may be monodisperse and polydisperse. For purposes of defining and describing the present invention, "monodisperse" polymers are polymers having a well defined simple molecular weight. For purposes of defining and describing the present invention, "polydisperse" polymers are polymers that have been subjected to proteolysis and have a molecular weight distribution. Once a suitable repeating protein has been synthesized and purified, it can be used to form systems that can provide controlled release of the active agents in any suitable formulation of the personal care product. For purposes of defining and describing the present invention, "active agent" will be understood as referring to an appropriate personal care product component, including, but not limited to, enzymes; vitamins; anti-oxidants, such as tocopherols; wetting agents such as lactic acid, alpha-hydroxy acids, natural wetting factor (NMF); hyaluronic acid fragrances; colorants; pigments; dyes; UV filters sun filters; lanolin; whiteners; algae thickening agents; plant extracts and preservatives. For purposes of defining and describing the present invention, "controlled release" means the release of at least one active agent from a system, which incorporates a repeating sequence protein polymer. By modifying the polymer properties and / or system design, including type, geometry and size, it is possible to obtain the release rate obtained in a specific period. The controlled release systems provide a rapid, slow or constant release depending on the degree of control of the optimal level and the optimal time of availability of the active ingredient. Controllable release mechanisms include, for example, diffusion through a speed control means, erosion of the biodegradable barrier material, or a combination of diffusion and erosion. Controlled release also includes triggered release, which occurs in the presence of external conditions, such as heat, pressure, electric fields, pH, salt concentrations, ionic strength, and solvents. In accordance with one embodiment of the present invention, a repetitive sequence protein polymer and at least one active agent are used to form a complex, and the complex is further processed to provide a system capable of providing controlled release of an active agent. For purposes of defining and describing the present invention, "complex" means the repetitive sequence protein polymer and the active agent associations wherein the repetitive sequence protein polymer interacts directly and passively with portions on the molecules of the active agent. Repetitive sequence protein polymers can be amphiphilic having hydrophilic and hydrophobic moieties. The hydrophilic portion can interact with active molecules via hydrogen bonds, van der aals interactions and / or ionic interactions. In addition, the hydrophobic portions can also interact as active agent molecules. According to one embodiment of the present invention, repeating sequence protein polymers can be used to form a complex with anionic molecules, and the complex can be further processed to provide a system, such as a matrix, gel, film or microparticle that can provide triggered controlled release of the anionic molecules in personal care products. A suitable repetitive sequence protein polymer can be used to form a complex with one or more anionic molecules. In general, the repeating sequence protein polymer will be selected to be cationic, and the complex will be formed by an ionic interaction between the repeating sequence protein polymer and an active agent. Examples of suitable anionic molecules include, but are not limited to, anionic enzymes, such as glucose oxidase, lipases and hydrolases, vitamin C, and alpha-hydroxy acids such as glycolic acid, lactic acid, malic acid, citric acid, mixed fruits, triple fruit acid and the like. The cationic repeating sequence protein polymer and the anionic molecule complex can be formed in any suitable manner, for example, a repeating sequence protein polymer can be formed in a complex with the glucose oxidase by the addition of the glucose oxidase to a solution of the repeating sequence protein polymer, with or without additives, such as plasticizers (for example, glycerol, PEG 200, triethanolamine, and the like). Once a suitable complex has been formed, the complex is further processed to provide a system that is capable of providing controlled release of the active agents. For example, the temperature of the complex may be high and the repetitive sequence protein polymer may undergo an irreversible gel-to-gel transition to form a water-insoluble hydrogel or film to provide controlled release properties. In a further example, the complex can be left at ambient temperatures for an adequate period of time, and a water insoluble hydrogel can be formed as the repetitive sequence protein polymer undergoes an irreversible transition from sol to gel. An insoluble film in water can be formed by evaporating the water. Once an adequate system has been formed, the system can be used to provide controlled release of the anionic molecule. In general, the anionic molecule can be released from the compound by changing the physical parameters of the complex environment. For example, the anionic molecule can be released by changing the ionic strength of the environment. When the ionic strength of the environment is increased, the charge-charge interaction of the complex can be accepted, and the anionic molecule can be released. According to yet another embodiment of the present invention, repeating sequence protein polymers can form complexes that have non-ionic interactions, and the complexes can form a material or carrier that can provide controlled release of the active agents. For example, hydrophobic-hydrophobic, non-polar van der Waals and hydrogen bond type interactions can be used to form the complexes of the present invention. The active agent can be hydrophilic or hydrophobic. For example, the repetitive sequence protein polymer and the active agents can show a hydrophobic-hydrophobic interaction and / or hydrogen bonds and / or van der Waals type interactions, and a complex can be formed. Once a suitable complex has been formed, the complex is further processed to provide a system that is capable of providing controlled release of the active agents. For example, the temperature of the complex may be high and the repetitive sequence protein polymer may undergo an irreversible transition from sol to gel to form a water insoluble hydrogel or film to provide controlled release properties. In a further example, the complex can be left at ambient temperatures for an adequate period of time, and a water-insoluble hydrogel can be formed as the repetitive sequence protein polymer undergoes an irreversible transition from sol to gel due to the evaporation of water. A film insoluble in water can be formed by evaporation of water. The release of the active agent from the system can be due to the diffusion through the protein repeating sequence, the erosion of the protein polymer of repetitive biodegradable sequence, the breakdown of the gel, the hydrolysis of the protein polymer by the protease present in the skin , or by any other suitable release mechanism. The repeating sequence protein polymer can act as a speed control polymer. The rate of release of the active agents from the appropriate repetitive sequence protein polymers can be altered by modification of the composition and sequence of the repeating sequence protein polymer and by modification of the size and geometry of the sequence protein polymer. repetitive with which the active agent has formed the complex. Examples of suitable hydrophilic active agents include, but are not limited to, enzymes, vitamin C, hyaluronic acid, and alpha-hydroxy acids. Examples of hydrophobic active agents include, but are not limited to, vitamin E, vitamin D3, and coenzyme Q-10. The repeating sequence protein polymer and the active agent complex can be formed in any suitable manner. For example, aqueous enzyme solutions can be added to an aqueous solution of the repeating sequence protein polymer. The temperature of the mixture can then be raised to cause an irreversible transition from sol to gel and form the water-insoluble gel containing the enzyme. The enzymatic solution of the repetitive sequence protein polymer can also form an insoluble film by evaporation of the water. The vitamin E acetate can be emulsified in an aqueous solution of the repeating sequence protein polymer prior to gel or film formation, as described above. In an alternative embodiment, repeating sequence protein polymers can be formed into complexes with suitable active agents, and the complexes can be used to form systems comprising microparticles that provide controlled release of the active agents. The microparticles can be formed by an emulsification / gelling method using a protein polymer of suitable repetitive sequence, which undergoes the irreversible transition from sol to gel. When a water-soluble active agent is used, the water-soluble active agent and a suitable repetitive sequence protein polymer can be aggregated together in an aqueous solution, so that a complex is formed. The water-soluble phase can then be emulsified in a second phase which is not miscible with the aqueous phase. For example, the second phase may be an organic phase or a silicone phase. The emulsion can then be trimmed until the desired droplet size is reached, and the emulsion can be heated in order to increase the gelation rate of the repeating sequence protein polymer. The technique results in small microparticles composed of the repetitive sequence protein polymer and an active agent embedded throughout the microparticles of the gel. The non-miscible phase can then be removed, and the microparticles can be added to the appropriate formulations of personal care products. When an active water insoluble agent is used, a two step oil / water emulsification / gelling process (O / W / 0) can be used. In the first step, the water insoluble active agent is emulsified in the aqueous solution of the repeating sequence protein polymer to form a complex. The emulsion is then added to another phase, or continuous phase, which is not miscible with the aqueous phase, and emulsified to form a 0 / W / O emulsion. The repetitive sequence protein polymer is subjected to irreversible transition from sol to gel by raising the temperature of the emulsion and the microparticles of the repetitive sequence protein polymer containing the active agent insoluble in water are thus formed. The remaining continuous phase can be removed. The water-soluble or water-insoluble agent can be released from the microparticles formed by the emulsification / gelation method by trimming because the microparticles are sensitive to shearing. Examples of suitable water-soluble active agents include, but are not limited to, enzymes such as hydrolases, proteases, lipases, oxidases, peroxidases, amylases, carbohydrolases, and superoxide dismutases. Examples of suitable oil-soluble active agents include, but are not limited to, vitamins E and D3. According to yet another embodiment of the present invention, repeating sequence protein polymers are used to form microparticles from which the active agents for use in personal care products can be released. However, in this embodiment, a complex between the repetitive sequence protein polymers and the active agents is not generally formed. The microparticles can be formed by interfacial polymerization reaction involving a repeating sequence protein polymer. For example, the repeating sequence protein polymer can be soluble in water and incorporated into a water-soluble phase. An oil-soluble monomer can be incorporated into an oil-soluble phase. The water-soluble phase and the oil-soluble phase are added together to form an emulsion, and an interfacial polymerization reaction is carried out after the formation of the emulsion. The interfacial polymerization reaction can occur at the oil / water interface to form a capsule wall from the repeating sequence protein polymer and the monomer. The suitable active agent, soluble in water, can be added to the water-soluble phase before the formation of the emulsion. The water soluble phase having the repetitive sequence protein polymer and the active agent, can be added to the oil-soluble phase having the oil-soluble monomer, to form a water / oil (W / O) emulsion before the interfacial polymerization reaction.

Alternatively, an oil-soluble active agent, suitable, can be incorporated into the oil-soluble phase containing an oil-soluble monomer, suitable. The oil-soluble phase having the active agent can be added to the water-soluble phase having a repeating sequence protein polymer, to form a 0 / W emulsion for the interfacial polymerization reaction. The interfacial polymerization reaction can be carried out at room temperature or the reaction mixtures can be heated in order to accelerate the interfacial polymerization. Thus, repeating sequence protein polymers can serve as encapsulating agents for water-soluble and water-insoluble active agents. Any suitable oil-soluble monomer can be used to form the particulates of the present invention. For example, suitable oil-soluble monomers that can react with repeating sequence protein polymers include, but are not limited to, isocyanates, epoxides, alkyl chlorides and acid chlorides. For example, an isocyanate monomer can react with an amine portion of a repeating sequence protein polymer. The active agent can be released from the microparticles in any suitable manner. For example, the active agent can be released by diffusion of the active agent out of the microparticle, - undergoing cutting after the application of the microparticles to the skin or hair, which disturbs the capsule wall and releases the active agent , or hydrolyzes the protein polymer by the protease present in the skin. For example, an oil soluble active agent can diffuse through the capsule wall after application. The size of the microparticles obtained by the emulsion / gelation or the interfacial polymerization methods can be determined by the amount of cut employed when the emulsion is formed. The microparticles containing the active agents can be added to any suitable personal care product. The microparticles of the repeating sequence protein polymer can be soft and deformable, to provide a desirable feeling after application to the skin, hair, nails, etc. The repeating sequence protein polymer can be biodegradable and its degradation product can be generally non-toxic. The microparticles of the present invention can allow the encapsulation and distribution of thermosensitive active agents such as enzymes, since the encapsulation process using the repetitive sequence protein polymers generally involves mild temperatures. In addition, active agents can be protected from deactivation by the presence of water or other agents such as sodium stearate which can be present in personal care product formulations, when the active agents are incorporated into the microparticles. It will be understood that systems incorporating the complexes of the active agent and the repeating sequence protein polymer, and the systems having microparticles formed by the interfacial polymerization of the present invention, may have more than one active agent, and the active agents may be the same as, or different from each other. In addition, the repeating sequence protein polymers of the present invention can be complexed with silicones, and silicones will generally not be released from the complexes and microparticles of the present invention. Rather, the repetitive sequence silicone and protein polymer complexes can be used to provide distribution and release of other active agents. Silicone, when incorporated into personal care compositions, is well known in the art for conferring benefits such as lubrication capacity, conditioning and moisture retention, and provides a desirable, non-greasy feel on the skin. Typically, silicone fluids are used in the form of aqueous emulsions for ease of incorporation into skin or hair care formulations. When incorporated into personal care compositions as a complex of silicone / repeating sequence protein polymer, it is believed that the silicone acts in synergy with the repeating sequence protein polymer to enhance the personal care benefits provided by the protein polymer and any associated active agents. In addition, the silicone acts to stabilize the repeating sequence protein polymer, increasing the solubility of the protein, due to the resulting formation of the stable emulsion, which thereby increases the efficacy of the personal care compositions to which it has been subjected. added the complex. In one embodiment, repeating sequence protein polymers are not generally hydrophobic, but also miscible in water, which distinguishes them from hydrolyzed forms. Proteins for which silicone provides distribution benefits, include fibrous or structural proteins in general, and in particular, silk-like / elastin-like proteins (SELPs), collagen and keratin. A specific embodiment employs silicone to provide distribution benefits for the application of genetically engineered forms of those proteins, and specifically, forms of "SELPs engineered by genetic engineering." An even more specific modality employs SELP47K (SEQ ID No. 19). In one embodiment, silicone is combined with genetically engineered forms of repeating sequence protein polymers in the form of emulsions, which improves the ease of distribution of these proteins in personal care products and, in particular, in compositions of personal care products applied to the skin or hair Continuous emulsions in silicone and aqueous continuous are possible, although personal care formulations are typically based on water, and therefore silicone-polymer emulsions protein of repetitive sequence, where the continuous phase is aqueous, they are desired for ease of distribution in such formulations. Repetitive sequence protein polymers are interfacially active and adsorbed at the silicone-water interface to stabilize the emulsions, either by themselves or in combination with the surfactants. The use of silicone in combination with the repetitively engineered protein polymers manipulated by genetic engineering allows the formulation of silicone emulsions with an aqueous continuous phase comprising approximately 95% by weight of the oily phase. One modality of the silicone-based method for improving the distribution of repetitive sequence protein polymers utilizes the silicone polyether surfactants (SPE). SPEs are characterized as amphiphilic, having a hydrophobic portion comprising silicone, and hydrophilic polyether tails. Without being bound by any theory, it is believed that SPE interacts with the repeating sequence protein polymer to form a complex that helps dissolve the protein, resulting in an increase in the effective solubility of the protein. A more specific embodiment is directed to a method for using silicone, to improve the distribution of repetitive sequence protein polymers, wherein the repetitive sequence protein polymer is an SELP. In a more specific embodiment, the SELP is SELP47K (SEQ ID No. 19). In another embodiment of the method that uses silicone to improve the distribution of repetitive sequence protein polymers, the repeating sequence protein polymer is added to silicone emulsions in an aqueous continuous phase. It is believed that the hydrophobic portions of the repeating sequence protein polymers adsorb to the surface of the silicone fluid droplets, dispersed, while the hydrophilic portions interact with the aqueous phase. A specific modality uses SELPs as the repeating sequence protein polymer, and a more specific modality utilizes SELP47K, as the repeating sequence protein polymer. The silicone-protein polymer emulsions of stable repetitive sequence show a high level of hysteresis, which means that they are sensitive to the order of mixing. The preparation of the emulsions with a continuous aqueous phase requires that the oily phase be added to the aqueous phase. In addition, the emulsions are sensitive to the mixing method. Aqueous emulsions comprising a high percentage of the emulsion in the dispersed phase must be prepared by emulsifying the oily phase to water, with mechanical stirring. Preferred surfactants when employed, are silicone surfactants, in particular, silicone polyether polymeric surfactants. While the methods of preparing these emulsions will be obvious to one of ordinary skill in the art, variations in the process by which the emulsions are prepared can result in silicone emulsion systems with different physical distributions of the emulsions. phases and of the protein polymers, producing a less effective emulsion distribution of the repeating sequence protein polymers. These methods result in the formation of highly stable light blue or creamy emulsions, formed with simple mixing. After dilution, the repeating sequence protein polymer is maintained on the emulsion interface and the dispersed phase remains stable. In a targeted embodiment the personal care compositions, the increased solubility of the protein and the synergy of the repeating sequence protein silicone-polymer with respect to the benefits of the personal care formulation, combine to comprise a product with benefits of unexpectedly high general care. In a specific personal care product modality, the stable repetitive sequence protein silicone-polymer comprises the dispersed phase, is incorporated into a personal care formulation directed to the care of the skin, whereby the complex can be uniformly distributed to the skin by means of dispersion. Systems that provide controlled release of the active agents of the present invention can be added to rinsing conditioners. The systems can be used in shampoos, gels, foams and other hair care products. The systems may be suitable for use in skin care products such as moisturizers, toning and makeup. The systems may also be suitable for use in nail products, such as varnishes or varnish removers. The systems may be present in any suitable amount in the product formulations. For example, the systems may comprise from about 0.001% to about 10% by weight of the composition. More generally, the systems may comprise about 0.01% to about 5% by weight of the composition, more preferably about 0.01% to about 1% by weight of the composition. In accordance with one embodiment of the present invention, the systems can be formulated in a variety of emulsions. The emulsions can provide wetting, softening, film formation, improvement of the sensation, optical effects, reinforcement, reaffirmation and conditioning properties. The emulsions may contain: It will be understood that the emulsions may also contain other suitable components. Suitable emulsifiers can be anionic, cationic or nonionic in nature. For example, suitable emulsifiers include, but are not limited to, TEA stearate, ethoxylated fatty acids, or alcohols. Suitable thickeners can be any combination of ingredients used to modify the viscosity of the product or the rheology thereof. The thickeners can be natural, and the natural thickeners can include silicas, magnesium and aluminum silicate, xanthan gum and alginates. The thickeners may alternatively be polymeric, and the polymeric thickeners may include crosslinked polymers of acrylate, polyacrylic acid and modified celluloses. The thickeners may also include crystalline agents such as "fatty acids and alcohols, and suitable crystalline agents" include stearyl alcohol or stearic acid The emollients may be any combination of one or more ingredients used to modify the feel of the product and the aesthetics Suitable emollients include: simple and complex esters such as isopropyl myristate and octyldodecyl stearoyl stearate, triglycerides such as capric / caprylic triglyceride, waxes such as carnauba wax and shea butter, vegetable and animal oils such as risino oil. , coconut oil and rice bran oil, fatty alcohols such as stearyl, myristyl, cetyl and behenyl alcohol, fatty acids such as stearic acid, lauric acid and oleic acid.

The opacifiers can be any combination of one or more ingredients used to modify the appearance of the product. Suitable opacifiers include, but are not limited to, fatty alcohols such as stearyl alcohol, myristyl alcohol, cetyl alcohol and behenyl alcohol, and fatty acids such as stearic acid, lauric acid, and oleic acid). Suitable humectants can be any combination of one or more ingredients used to retain moisture in the formula and impart hydration to the user. Suitable humectants include, but are not limited to, glycerin, polypropylene glycol, and sorbitol. The functional ingredients may be any combination of one or more ingredients added to impart a specific effect when used, and may be added to the personal care formulation in addition systems capable of providing controlled release of the active agents. These may include: UV absorbers, such as octyl methoxycinnamate, benzophenone 3, titanium dioxide, and octyl salicylate; film-forming agents such as VP / Eicosene copolymer, cosmetic-pharmaceutical agents, such as peptides and proteins, alpha-hydroxy acids and retinol and retinoic acid derivatives; antioxidants such as tocopherol and derivatives thereof, and ascorbic acid and derivatives thereof; vitamins such as B, D, K and their derivatives; antiperspirant active agents such as aluminum hydroxide and zirconium hydroxide, depilation agents such as thioglycolate salts; anti-acne agents such as salicylic acid and benzoyl peroxide; abrasives and exfoliants such as silicates, pumice and polyethylene; and extracts of plants, fruits, plant or marine sources. Suitable preservatives can be any combination of ingredients approved by the regulatory agencies and acceptable for use in cosmetic applications. For example, methyl- and propyl-paraben, imidazolidinyl-urea, and ascorbic acid can be used as preservatives. The finishing ingredients may be any combination of one or more ingredients added to adjust the characteristics of a formula. Finishing ingredients may include: fragrances; colors; chelating agents such as tetrasodium EDTA; and pH buffers such as citric acid and phosphoric acid and salts thereof. Those skilled in the art can modify the illustrative emulsion formulation for a variety of personal care applications. The formula in emulsion can be used to form creams, lotions, moisturizers, facial cleansers, hair removers, masks, sun care products, antiperspirants, acne products, make-up bases, hair conditioners, hair relaxers, treatments of the hair, masks, products for the nails, products for the lips, products for shaving, and toothpastes and the like. According to yet another embodiment of the present invention, the systems of the present invention can be formulated in a variety of surfactant systems. Surfactant systems can provide a number of properties for personal care products, including wetting, softening, film formation, improvement of skin feel, optical effects, strengthening, firming and conditioning. Typical surfactant systems may contain, but are not limited to, the following components:Water css Primary Surfactant (s) 0.1-15% Secondary Surfactant (s) 0.1-10% Rheology Modifier (s) 0.1-5% Alcohol (s) 0-25% Functional Ingredient (s) (en) 0-10% Conditioning value (s) 0-5% Conservative (s) css Finishing component (s) css Systems capable of providing 0.001-10% Control release It will be understood that additional suitable components can be included in the surfactant systems, the primary surfactants can be any combination of one or more ingredients used to reduce surface tension or create a foam. The surfactants may include: anionic surfactants such as alkyl sulfates, ether sulfates, alpha-olefin sulfonates and soap; amphoteric surfactants such as glycosides, glutamates, carboxylates, isethionates, carboxylates, glycinates and lauramphoacetates; ampholytic surfactants such as betaines and sultanates; or non-ionic surfactants such as fatty alcohol ethoxylates, fatty acid ethoxylates and amine oxides. The secondary surfactants can be any combination of one or more ingredients used to modify the foam characteristics and quality, to stabilize the foam, or reduce irritation. These may include, for example, cocoamidopropyl betaine, monoethanolamides, and diethanolamides. Suitable rheology modifiers can be any combination of one or more ingredients used to modify the appearance of the product, the viscosity or the rheology thereof. The rheology modifiers can be natural, rheology modifiers, including salts, silicas, magnesium aluminum silicate, xanthan gum, guar derivatives, and alginates. The rheology modifiers may be polymeric rheology modifiers including crosslinked acrylate polymers, crosslinked cellulosic materials and polyacrylic acid. These may also include opacifiers and crystalline agents such as fatty acids and alcohols including stearyl alcohol or stearic acid. Suitable alcohols can be any combination of one or more ingredients added to provide astringency, cooling, volatility or solubilization. For example, suitable alcohols include ethanol and isopropanol. The functional ingredients may be any combination of one or more ingredients added to impart a specific effect when used. These may include: UV absorbers such as octyl methoxycinnamate and benzophenone-3; styling and film forming agents such as polyvinyl pyrrolidone (PVP) and PVP / polyvinyl alcohol (PVA) copolymers; cosmeceutical (cosmetic-pharmaceutical) agents such as peptides, proteins, alf-hydroxy acids, retinal and retinoic acid derivatives; antioxidants such as tocopherol and derivatives thereof, and ascorbic acid and derivatives thereof; vitamins such as vitamins B, D, K and their derivatives; anti-acne agents such as salicylic acid and benzoyl peroxide; anti-dandruff agents such as zinc pyrithione and selenium sulfide; and conditioning agents such as cationic agents and extracts from plants, fruits, vegetables or marine sources.

The conditioning agents may be any combination of one or more added ingredients to impart wetting, skin feel, softening, anti-static or gloss effects. Suitable conditioning agents may include: cationic polymers such as polyquaternium-10 and polyquaternium-11; quaternized fatty acids such as cetyl trimethyl ammonium chloride; animal or vegetable proteins and their derivatives, such as hydrolyzed wheat protein and hydrolyzed collagen; silicone derivatives such as dimethicones, amodimethicones, phenyl trimethicones, and volatile silicones; emollient oils such as isopropyl myristate and capric / cationic triglyceride; and humectants such as glycerin and propylene glycol. Those who have experience in the technique, can modify this illustrative formula of the surfactant system for a variety of applications for personal care. For example, the formula of the surfactant can be modified to form shampoos, body cleansers, facial cleansers, hair conditioners, hair gels, hair treatments, facial toning, fragrance products, and mouthwashes, and the like. In accordance with one embodiment of the present invention, a silk-elastin polymer SELP47K (SEQ ID No. 19) can be used as the repeating sequence protein polymer of the present invention. The SELP47K is a single block protein polymer consisting exclusively of crystalline blocks similar to silk and flexible blocks similar to elastin. SELP47K is more linear than many proteins, because it has a two-dimensional beta-sheet structure instead of a three-dimensional structure of alpha helix. SELP47K show the ability to self-assemble by cross-linking the beta sheets into fibers. SELP47K is 70% proline, valine, and alanine, and has hydrophobic characteristics. Additionally, SELP47K has a high proportion of lysine. In order that the invention may be more easily understood, reference is made to the following examples, which are intended to be illustrative of the invention, but are not intended to be limiting in scope. EXAMPLES EXAMPLE 1 A block copolymer of repetitive sequence protein, silk, elastin, engineered by genetic engineering (SELP) was isolated and purified from E. coli bacteria. The E. coli containing a recombinant DNA of the SELP47K copolymer of the silk-elastin repeat sequence protein was obtained from Protein Polymer Technologies, Inc. (PPTI) of San Diego, California. The ?. coli can be prepared according to the methods described in U.S. Patent Nos. 5,243,038 and 6,355,776. The recovery of quantities in kilograms of SELP was also demonstrated. The silk-elastin SELP47K copolymer had a general head structure- [(GAGAGS) 2 (GVGVP) 3GKGVP (GVGP) 4 (GAGAGS) 2] 13-tail (SEQ ID No. 19). The copolymer contained 886 amino acids, with 780 amino acids in the repetitive sequence unit. The SELP47K had a molecular weight of approximately 70,000 Daltons, and the pl of the protein is 10.5 The monodisperse silk-elastin protein polymer SELP47K was produced for the application test as follows: fermentation of E. coli was performed to produce a cell paste containing monodisperse SELP47K. The cell paste was cast in ice-cold water and homogenized to make the cell extract. The cell extract was mixed with polyethyleneimine and a filter aid, and allowed to stir at 7 ° C for one hour. Polyethyleneimine caused the precipitation of cellular debris and a significant amount of E. coli proteins. The reaction mixture containing SELP47K was then filtered using the Rotary Drum Vacuum Filter (RDVF). The filtered SELP47K solution was then mixed with ammonium sulfate at a saturation of 25%, which led to the precipitation of SELP47K. The precipitated SELP47K and the mother liquor were mixed with a filter aid, and again filtered using RDVF. The RDVF cake containing SELP47K and the filter aid was mixed with cold water to dissolve the SELP47K. This step of precipitation and solubilization was repeated once more to improve the purity profile of the SELP47K. SELP47K purified, monodisperse was then exchanged with water until the conductivity of the SELP solution reached 50 μS / cm2. The monodisperse SELP solution was then concentrated to 10% w / v and then lyophilized to make the polymer of the monodisperse, powdered SELP47K protein. The material was stored at -70 ° C until it was necessary for the application test. B. Variants of SELP were either obtained from PPTI or manipulated by genetic engineering (Table 1). Table 1. SELP variants, properties The E. coli strains containing recombinant DNA from SELP47L, SELP37K and SELP27K copolymer of repeating silk-elastin sequence protein were also obtained from Protein Polymer Technologies, Inc., of San Diego, California. The variant proteins SELP67K, SELP58, SELP37K and SELP27K were produced in a batch culture fed with 14 liters using standard SELP47K production protocols., as described above. The proteins were purified and characterized as follows: 40 grams of cell pastes harvested from 14 liter cultures were used by means of a French press, followed by the addition of polyethylenimine (0.8% w / v). The centrifugation was used to separate the cell debris from the cell extract. The SELP polymers were precipitated from the extract using ammonium sulfate (30% saturation), harvested by centrifugation and reconstituted in water. The residual salts were removed by dialysis against water and the SELP polymers were lyophilized and characterized using sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The SELP47K-3 species was excised from the SDS-PAGE gels and further characterized, its identity confirmed by LC-MS / MS (Liquid Chromatographic Mass Spectroscopy). The molecular weight of the intact SELP47K-3 protein was also confirmed using MALDITOF / MS (Laser-Destroyed Ionization Flight Time Mass Spectrometry assisted by Matrix). The protocol used for the genetic engineering of the variants SELP47E, SELP47K-3, SELP47R-3 and SELP47E is a modification of a commercially available equipment designed to create simple changes of base pairs at multiple sites along a particular DNA sequence (QUIRCHANGE® Muíti (Site-directed Mutagenesis Team), Stratagene catalog # 200513). The standard protocol involves the construction of 5 '-phosphorylated single-direction primers, which will hybridize to template regions of the plasmid of interest and incorporate point mutations. The thermocycling is employed, which includes a ligation reaction designed to bind multiple primers during each round of synthesis. The SELP DNA sequences are unique, since the multiple repetitive subunits are identical. In order to change a simple amino acid residue, in all subunits, a simple change is effectively made multiple times. The previous protocol was additionally modified since the primers were designed in pairs, complementary, creating PCR amplification conditions in the thermocycling process. The amplified plasmid DNA was then used to transform E. coli cells and can also be selected and characterized for desired mutations.

Methods: Conversion of SELP plant residues Primers were designed to direct a single base change mutation, which results in the conversion of lysine residues to glutamic acids or arginines, while simultaneously creating a unique restriction enzyme site on this site, used for subsequent selection with plasmid. The 5'-phosphorylated primers were made complementary, in both directions (both strands) as follows. Conversion of glutamic acid: 5'-GGGAGTTGGTGTACCTGGAGAAGGTGTTCCGGGGGTAGG-3 '(SEQ ID No. 21) 3' -CCCTCAACCACATGGACCTCTTCCACAAGGCCCCATCC-5 '(SEQ ID No. 22) (A20 was converted to G20) Conversion of arginine: 5'-GGGAGTTGGGGTACCTGGACGAGGTGTTCCGGGGGTAGG-3 '(SEQ ID No. 23) 3' -CCCTCAACCCCATGGACCTCGAGGTGGAACCCCCCCATCC-5 '(SEQ ID No. 24) (G19 and T20 were converted to C and G) The QUIKCHANGE® multi reaction was carried out following the manufacturer's protocol, except that both complementary primers were excluded. 5μl of each reaction were used to transform the TOP10 cells following the protocol (Invitrogen) '. 100 μl of optimized carbon overgrowth with salt (SOC) were plated by reaction. Transformants were collected and developed in 5 ml of LB medium containing 50 ppm of kanamycin. Plasmid DNA was obtained from the cultures using the Qiagen plasmid minipreparation kit and analyzed by digestion with appropriate restriction enzymes followed by gel electrophoresis. The constructions that seemed correct were confirmed by DNA sequencing. Several rounds of the internal protocol were required to obtain the SELP47E variant. In all cases, this method resulted in the creation of a library consisting of variants that span a range of subunits. That distribution was in the range of 1 to 17 subunits. SELP47E-3 and SELP47R-3 were a result of this distribution. SELKP47E-3 resulted from the use of the above methods to convert the glutamic acids of SELP47E-3 back to Usinas. Successful construction plasmids were used to transform E. coli MM294 using Lauryl Bertni plates (LB) containing 50 ppm kanamycin. Simple colonies were collected and developed in 60 ml of TM2 (recipe) + 2% glucose, 50 ppm of kanamycin in 500 ml Erlenmeyer flasks, with gutter, at 30 ° C, 250 rpm, 16 hours. The cell culture was supplemented with glycerol (10% v / v), and aliquots of 1.5 ml were placed in cryopharas and stored at -80 ° C. The random bottles were tested for contamination by incubation of 10 μl of inoculation loopfuls on LA plates + 1.6% skim milk, at 37 ° C, for 16 hours. The integrity of the plasmids was also confirmed using plasmid purification, and analysis using restriction enzyme digestion / in gel electrophoresis, as well as DNA sequencing. Frozen cryophrasics were prepared using methods known in the art, and used as seed stocks for subsequent cultivation, for protein production. The variant proteins SELP47K-3, SELP47E-3 and SELP47R-3 were produced in batch-fed culture of 14 liters, using the standard SELP47K production protocols, previously used. The proteins were purified and characterized as follows: 40 grams of cell pastes harvested from 14 liter cultures were lysed by means of a French press, followed by the addition of 0.8% w / v polyethylene imide. The centrifugation was used to separate the cell assay from the cell extract. The SELP polymers were precipitated from the cell extract using ammonium sulfate (30% saturation), harvested by centrifugation and reconstituted in water. The residual salts were removed by dialysis against water and the SELP polymers were lyophilized and characterized using polyacrylamide and sodium dodecyl sulfate gel electrophoresis (SDS-PAGE). The SELP47K-3 species was excised from the SDS-PAGE gels and additionally characterized, your identity confirmed by LC-MS / MS. The molecular weight of the intact SELP47K-3 protein was also confirmed using MALDI-TOF / MS. -M3H + 1641, M4H + 1231 of the silk-elastin unit ~ 5 kDa. EXAMPLE 2 The purification and preparation of the polydispersed silk-elastin protein polymer for the application test was carried out in the following steps. A cell separation of the fermentation broth was performed using microfiltration. A cell disintegration to make a cell extract was carried out using a French press. The cell extract was separated from cell waste using polyethyleneimide and a filter aid. The cell extract was mixed with ammonium sulfate to a saturation of 25% to precipitate the silk-elastin protein polymer. The precipitated silk-elastin polymer was further purified by dissolving it in water and precipitating it with ammonium sulfate. In order to prepare a polydispersed silk-elastin protein polymer, the precipitated silk-elastin protein polymer was again dissolved in water and mixed with a trace amount of the commercial protease.

The commercial protease was then inactivated and destroyed by treatment with acid. The polydispersed silk-elastin protein polymer was then ultrafiltered until the solution of the silk-elastin protein polymer reached a conductivity of 50 μS / m2. The solution of the polydispersed silk-elastin protein polymer was concentrated to 10% by weight and then lyophilized. The polydispersed silk-elastin protein polymer powder, lyophilized, was stored at -70 ° C until use. The lyophilized polydispersed silk-elastin protein was then dissolved in deionized water to a desired concentration for the hair application test. EXAMPLE 3 The purification and formation of the monomer unit of SELP47K (molecular weight of 4920 kDa) was carried out using the monodisperse material of SELP47K produced as in example 1. The monidisperse SELP47K was dissolved in water and treated with the protease endopeptidase lysC (Sigma Chemical Company) specific to break the protein in the lysine residue, for 30 minutes, at room temperature. The lysC protease was then inactivated and destroyed by treatment with acid. The monomeric unit of SELP47K was then ultrafiltered until the conductivity of the protein polymer solution reached 50 μS / m2.

EXAMPLE 4 A film of SELP47K and anionic glucose oxidase (Gox) was formed in the following manner. A 12% solution of SELP47K was prepared by adding 1.8 g of SELP47K to 13.2 g of milliQ water (pH 6.5). The solution was stirred with a magnetic bar for 15 minutes. A Silverson mixer with a small head at 4000 rpm was used for 2 minutes until the complete solution of SELP47K (no lumps) was obtained. A stock solution of ~ 0.0647 g of Gox and 0.06 g of glycerol was added to 0.7 g of the 12% SELP47K solution, and the resulting mixture was stirred with a magnetic bar for 10 minutes at 300 rpm. The SELP47K / Gox mixture was grown on a ylar sheet which was placed at 37aC for 17 hours uncovered for the film to dry. The film was cooled to room temperature. EXAMPLE 5 A study of the rate of release of Gox from the SELP47K and Gox film was conducted as follows. Portions of the film prepared according to Example 3, were weighed accurately and mounted on a 2.5 cm spherical glass piece using cement glue, and allowed to dry for 30 minutes. The study of the release rate of Gox from the film was carried out using a Hanssen solution tester at 30 ° C. The glass-mounted samples were placed inside a dissolution vessel of 150 ml, narrow with the films facing upwards. 25 ml of buffer was added. A film sample had a milliQ water damper. Another one for the film sample had a 0.2 M sodium phosphate buffer of pH 7.65. A small paddle that was placed just below the cushion surface and rotated at a speed of 25 rpm, provided agitation of the sample. The samples of 0.5 ml were removed at 10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 16 hours and 24 hours, and were evaluated for the activity of the enzyme. The Gox assay was conducted using a wavelength of 410 nm at 25 ° C and a reaction time of 10 minutes. An aliquot of 50 μl of the sample was added to 1000 μl of the substrate solution (x 21) and evaluated for Gox activity. The concentration of Gox was calculated as follows: [Gox] (mg / ml) = (ratio OD / minute) * (0.6 μg / 1000 mg) * Dilution x 21 * Dilution * 25. When the 0.2 M sodium ionic phosphate buffer is added to the film, Gox is released in a controlled manner. EXAMPLE 6 A hydrogel incorporating a polymer of SELP47K and Gox was prepared in the following manner. A 12% SELP47K solution was made by adding 2.4 g of SELP47K to 17.6 g of milliQ water (pH 6.5). The solution was stirred with a magnetic bar for 15 minutes. We used a Silverson mixer with a small head at 4000 rpm for 2 minutes, until the complete dissolution of SELP was obtained (without lumps). 0.08 g of a Gox stock solution was added to ~ 14.97 g of the 12% SELP solution and the resulting mixture was stirred with a magnetic bar for 10 minutes at 6000 rpm. ~ 3.0 g of the mixture was filled into a small plastic container (Rotronic) which was then sealed and sealed with parafilm paper. The vessel was placed at 37 ° C for 17 hours. After 17 hours, the hydrogel was cooled to room temperature. EXAMPLE 7 A Gox release rate test from the hydrogel formed according to Example 6 was conducted in the following manner. 1 ml of milliQ water was added to wash the upper surface of the hydrogel in the plastic container. The vessel was shaken twice and the wash was removed. The release rate in the milliQ water was studied by adding 5 ml of milliQ water in the plastic container, on top of the hydrogel. The vessel was closed and then gently agitated on a shaker at ~ 50 rpm. At several time points, 60 μl samples of the dissolution medium were collected and evaluated for Gox activity as described in example 11. The release rate in the 0.5 M sodium phosphate buffer was studied by replacement of the milliQ water per 0.5 M sodium phosphate buffer, pH 7.5 after 28 hours. The release rate test as described above in Example 11 was conducted. Sodium phosphate 0.5 M ionic facilitated the release of Gox. Gox was stored for 17 hours at 37 ° C and for 28 hours at room temperature. The initial activity of Gox was observed. Gox showed 66.59 mg / ml of activity after 17 hours and 66.75 mg / ml of activity after 28 hours. No degradation of the enzyme was observed. EXAMPLE 8 The microparticles formed from Gox using SELP47L can be prepared in the following manner. A 12 wt% aqueous solution of SELP47K is prepared by 2.4 g of SELP47K to 16.6 g of MilliQ water (pH 6.5). The mixture is then mixed using a Silverson mixer at 4000 rpm for 2 minutes, until complete dissolution of SELP47K is obtained. Add 0.08 g of glucose oxidase solution (Gox) to 14.97 g of the 12% aqueous solution of SELP47K and stir with a magnetic bar for 10 minutes to obtain a homogeneous solution of Gox and SELP to form the water-soluble phase . 2.25 g of a surfactant formulation aid (Dow Corming 3225C) are then mixed with 30 g of silicone oil, 1000 CTs (Dow Corming) and added to a 50 ml vessel to form the oil-soluble phase. A marine impeller is submerged approximately half the depth of the liquid. The SELP47K microparticles containing Gox are produced by an emulsification / gelation method. The SELP / Gox solution prepared above (15 g) is dispersed in the silicone oil and emulsified at 400 rpm for 15 minutes. The temperature of the emulsion is then brought to 37 ° C to initiate gelation of the emulsified SELP droplets, and mixing is continued for 3 hours. The individual SELP47K microparticles containing the Gox suspension in oil are thus obtained and can be mixed into a personal care formulation. The individual SELP47K microparticles containing the Gox suspension in oil can also be added to a 200 ml container containing 100 ml of milliQ water. The SELP47K microparticles settle in the lower aqueous phase, leaving the upper oily phase clear. The silicone oil is sucked and discarded. The microparticles are then washed with 0.5% Tween 80 surfactant solution, several times until the microspheres are free of oil. The SELP microparticles containing Gox suspended in milliQ water is then mixed into a personal care (water based) formulation such as oil / water cream., lotions, shampoos, and the like. EXAMPLE 9 Microparticles formed around Gox using SELP47K can be prepared in the following manner. A 12 wt% aqueous solution of SELP47K is prepared by the addition of 2.4 g of SELP47K to 16.6 g of MilliQ water (pH 6.5). The mixture is mixed using a Silverson mixer at 4000 rpm for 2 minutes, until complete dissolution of SELP47K is obtained. 0.08 g of a glucose oxidase solution (Gox) can be added to 14.97 g of the 12% aqueous solution of SELP47K, and stirred with a magnetic bar for 10 minutes to obtain a homogeneous solution of Gox and SELP, to form the phase soluble in water. 30 ml of hump oil are mixed with 2.25 g of the Dow Corning 5200 formulation aid which is then added to a 50 ml vessel to form the oil soluble phase. A marine impeller is submerged approximately half the depth of the liquid. SELP47K microparticles containing Gox are produced by an emulsification / gelation method. The previously prepared SELP47K / Gox solution (15 g) is dispersed within the silicone oil and emulsified at 400 rpm for 15 minutes. The temperature of the emulsion is then brought to 37 ° C to initiate gelation of the emulsified SELP droplets, and mixing is continued for 3 hours. The individual SELP47K microparticles containing the Gox suspension in oil are thus obtained and are subsequently mixed into a personal care formulation. The individual SELP47K microparticles containing the Gox suspension in oil can also be added to a 200 ml container containing 100 ml of milliQ water. The SELP47K microparticles settle in the lower aqueous phase, leaving the upper oily phase clear. Jojoba oil is aspirated and discarded. The microparticles are then washed with a 0.5% Tween 80 surfactant solution, several times until the microparticles are oil-free. The SELP microparticles containing Gox suspended in milliQ water are then mixed into a personal care (water based) formulation such as O / W cream, lotions, shampoos, and the like. EXAMPLE 10 SELP47K microparticles containing vitamin E surrounded by SELP47K, can be prepared using the following method. An organic phase containing vitamin E is prepared by mixing 15 g of vitamin E, 15 g of the solvent Aromatic 100 and 2 g of the isocyanate monomer (polymethylene polyphenylisocyanate) to obtain a homogeneous phase. An aqueous phase containing SELP47K can also be prepared. A 20% by weight aqueous solution of the SELP first elaborated by the addition of 10 g of SELP to 40 g of milliQ water (pH 6.5). The mixture is then mixed using a Silverson mixer at 4000 rpm for 2 minutes, until the complete dissolution of the SELP47K is obtained. Next, a surfactant is added to facilitate the emulsification of the organic phase. Specifically, 37.5 g of a 4% aqueous solution of alcohol ethoxylate tergitol from Union Carbide is added and mixed with 10 g of the 20% by weight SELP solution. Protective colloid is also added to improve the stability of the emulsion. For example, 5 g of an aqueous solution of 10 wt% PVA (Mowiol 4-88 from Clariant Corporation) together with 15 g of milliQ water are added. The aqueous phase is mixed to obtain a homogeneous phase before the addition of the organic phase, and added to a 50 ml vessel. A marine propeller is immersed approximately half the depth of the liquid. The organic phase is then emulsified in the aqueous phase containing SELP47K. The previously prepared aqueous phase is stirred at 180 rpm while the organic phase is gradually introduced. The agitation of the mixture is then increased to 400 rpm for 15 minutes after the entire organic phase is introduced. The emulsion is then transferred to a water bath and then light agitation is provided at 250 rpm. The emulsion temperature is brought up to 37 ° C, to allow interfacial polymerization between SELP and the isocyanate monomers and stir at 37 ° C, for 3 hours. EXAMPLE 11 The distribution of SELP47K (SEQ ID No. 19) in a personal care formulation using silicone polyethers was carried out as follows: 1.08 of the silicone polyether DC193 were collected in water (at 5.5% w / w) and mixed with 6.75 g polydimethylsiloxane 200 centistoke fluid (CS). The mixture was allowed to stand for 30 minutes. SELP47K (1.08 g, 5.5% w / w, for example, mass ratio 1: 1 to DC 193) was added to this mixture. The mixture was cut until it was soft (10 minutes) at 900 rpm using an agitator. The resulting complex of SELP47K-silicone had a bluish appearance and was a stable emulsion. This emulsion, when analyzed by microscopy, revealed a continuous, essentially aqueous phase with the protein surrounding the disperse, discrete silicone phase. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

Having described the invention as above, the content of the following claims is claimed as property: 1. A system for providing controlled release distribution of an active agent, characterized in that it comprises: a repeating sequence protein polymer; at least one active agent, wherein the repetitive sequence protein polymer and at least one active agent form a complex. The system according to claim 1, characterized in that the repetitive sequence protein polymer comprises a repetitive amino acid sequence unit, derived from elastin, collagen, abductin, biso, flageliform silk, trailing cable silk, the subunit of the high molecular weight gluten, titin, fibronectin, leminin, gliadin, glue polypeptide, ice nucleation protein, keratin, mucin, RNA polymerase II, highlight or a mixture thereof.
3. The system according to claim 1, characterized in that the formula of the repeating sequence protein polymer comprises: Ty [(An) x (B) b (A'n.) X '(B'.} B, ( A'V) x-] T'y.

wherein: T and T 'each comprise the amino acid sequence of 1 to 100 amino acids, wherein the amino acid sequence of T' is the same as or different from the amino acid sequence of T; and e and 'are each an integer from 0 to 1, where the integer of y' is the same as or different from the integer of y; A, A 'and A "are each individual repeating sequence units comprising from 3 to 30 amino acids, wherein the amino acid sequence of A' and the amino acid sequence of A" are the same as or different from the amino acid sequence of A; n, n 'and n "are integers of at least 2 and not more than 250; x, x' and x" are each 0 or an integer of at least 1, where each integer varies to provide at least 30 amino acids in A, A 'and A ", individual repetitive sequence units, and wherein the integer of x' and the integer of x" are the same as, or different from, the integer of x; B and B 'each comprise an amino acid sequence of 4 to 50 amino acids, wherein the amino acid sequence of B' is the same as or different from the amino acid sequence of B;

b and b 'each are integers from 0 to 3, where the integer of b' is the same as o. different from the integer of b; i is an integer from 1 to 100.
4. The system in accordance with the claim

3, characterized in that T and T 'comprise an amino acid sequence of 1 to 60 amino acids.
5. The system according to claim 3, characterized in that T and T 'comprise an amino acid sequence with less than 20% of the total number of amino acids in the repeating sequence protein polymer.
6. The system according to claim 3, characterized in that B comprises a sequence of amino acids with a biological or chemical activity.
7. The system in accordance with the claim

3, characterized in that B 'comprises an amino acid sequence with a biological or chemical activity. The system according to claim 3, characterized in that i is an integer from 1 to 50. 9. The system according to the claim

3, characterized in that i is an integer from 1 to approximately 30. The system according to claim 3, characterized in that A, A 'and A "comprise at least one sequence selected from the group consisting of SEQ ID No. 1, SEQ ID No. 3, SEQ ID No. 4, SEQ ID No. 5, SEQ ID No. 6, SEQ ID

DO NOT. 7, SEQ ID No.
8, SEQ ID No.
9, SEQ ID No.
10, SEQ ID No.

11, SEQ ID No. 12, SEQ ID No. 13, SEQ ID No. 14, SEQ ID No.

15, SEQ ID No. 16, SEQ ID No. 17, SEQ ID No. 18, SEQ ID No. 20, and combinations thereof.
11. The system in accordance with the claim

3, characterized in that A, A 'and A "comprise at least one sequence selected from the group consisting of SEQ ID No. 1,

SEQ ID No. 3 and combinations thereof.
12. The system in accordance with the claim

1, characterized in that the repetitive sequence protein polymer comprises SEQ ID No. 19.
13. The system according to the claim

1, characterized in that the complex is formed by the ionic interaction between the repetitive sequence protein polymer and at least one active agent, and wherein at least one active agent comprises anionic molecules, and the repetitive sequence protein polymer comprises cationic molecules.
14. The system in accordance with the claim

1, characterized in that an active agent is selected from the group consisting of anionic and alpha-hydroxyacid enzymes.
15. The system in accordance with the claim

1, characterized in that an active agent comprises at least one anionic enzyme selected from the group consisting of glucose oxidase, lipase, hydrolase and combinations thereof.
16. The system according to claim 1, characterized in that at least one active agent comprises glucose oxidase.
17. The system according to claim 1, characterized in that the complex is formed by non-ionic interaction between the repeating sequence protein polymer and at least one active agent.
18. The system in accordance with the claim

17, characterized in that the non-ionic interaction between the repeating sequence protein polymer and at least one active agent is hydrophobic.
19. The system according to claim 1, characterized in that the system is formulated as a matrix, emulsion, gel, hydrogel, film or microparticles.
The system according to claim 19, characterized in that the controlled release distribution is a triggered release distribution.
21. The system in accordance with the claim

1, characterized in that the repetitive sequence protein polymer and at least one active agent form microparticles and wherein the active agent is insoluble in water or soluble in water.
22. The system according to claim 21, characterized in that the active agent is a water soluble active agent, and the microparticles are formed by the emulsion / gelation method comprising: (1) combining the active agent soluble in water and the repetitive sequence protein polymer to form a complex in aqueous solution; (2) emulsify the complex as a water-soluble phase in a non-miscible phase so that the water-soluble phase forms droplets of dispersed phase and the immiscible phase forms a continuous phase; (3) cutting the dispersed phase droplets to a desired size; and (4) the withdrawal of the continuous phase.
23. The system according to claim 21, characterized in that the active agent is a water insoluble active agent and the microparticles are formed by an emulsion / gelation method comprising: (1) emulsifying the water insoluble active agent in a aqueous solution of the repetitive sequence protein polymer, to form an emulsion comprising a complex; (2) emulsifying the emulsion of (1) as a water-soluble phase, in an immiscible phase, so that the water-soluble phase forms droplets of dispersed phase and the immiscible phase forms a continuous phase;
(3) cutting the dispersed phase droplets to a desired size, and (4) withdrawing the continuous phase. The system according to claim 21, characterized in that the microparticles comprise capsules formed by the interfacial polymerization between the repetitive sequence protein polymer and a suitable monomer, wherein the capsules comprise at least one active agent encapsulated by the protein polymer of repetitive sequence, formed by the interfacial polymerization.
25. The system according to claim 21, characterized in that the microparticles comprise more than one active agent, which may be the same or different.
26. The system according to claim 1, characterized in that it is formulated in an emulsion comprising, by weight of the composition of the emulsion:
27. The system according to claim 1, characterized in that it is formulated in a surfactant system comprising, by weight of the composition of the surfactant system:
28. The system in accordance with the claim

1, characterized in that it is incorporated into a composition for personal care.
29. The system according to claim 28, characterized in that the personal care composition comprises a hair care composition, a skin care composition, a nail care composition, a cosmetic composition, a composition for oral care, or a pharmaceutical composition of free acquisition.
30. The system according to claim 28, characterized in that the system comprises from 0.001% to 0% by weight of the composition for personal care.
31. The system according to claim 28, characterized in that the system comprises 0.01% to 5% by weight of the composition for personal care.
32. The system according to claim 28, characterized in that the system comprises 0.01% to 1% by weight of the composition for personal care.
33. The system according to claim 1, characterized in that at least one repetitive sequence protein polymer comprises a silk-elastin-like protein, engineered by genetic engineering.
34. The system according to claim 33, characterized in that the gene-engineered protein similar to silk-elastin comprises SELP47K (SEQ ID No. 19).
35. The system according to claim 33, characterized in that the complex is in the form of an emulsion.
36. The system in accordance with the claim

35, characterized in that the emulsion further comprises a continuous aqueous phase and a dispersed oily phase, and wherein the continuous aqueous phase comprises up to 95% by weight of the dispersed oily phase.
37. The system according to claim 35, characterized in that the emulsion is incorporated into a personal care composition.
38. The system according to claim 37, characterized in that the composition for personal care comprises a formulation for the care of the skin or hair.
39. A method for manufacturing a personal care composition, characterized in that it comprises the combination of a system for providing controlled release distribution of an active agent with a physiologically acceptable carrier or excipient, to obtain a composition for personal care, wherein the system comprises a repeating sequence protein polymer and at least one active agent, and wherein the repetitive sequence protein polymer and at least one active agent form a complex.
40. A method in accordance with the claim

39, characterized in that the system comprises complexes of silicone-protein polymer of repetitive sequence.
41. A method in accordance with the claim

40, characterized in that they are complex formed from the interaction of the silicone polyether surfactant and a repetitive sequence protein polymer in aqueous solution.
42. A method according to claim 40, characterized in that complexes are formed from the interfacial interaction of the repetitive sequence protein polymer and the silicone at a silicone-water interface of a silicone emulsion having a continuous aqueous phase.
43. A method according to claim 40, characterized in that the repetitive sequence protein polymer comprises a silk-elastin-like protein, a collagen or a keratin, or some combination thereof.
44. A method according to claim 40, characterized in that the repetitive sequence protein polymer comprises a silk-elastin-like protein.
45. A method according to claim 40, characterized in that the repetitive sequence protein polymer comprises the silk-elastin-like protein, SELP47K (SEQ ID No. 19).