KR100796817B1 - Growth factor for hair and skin treatment - Google Patents

Abstract

This invention uses EGF, bFGF, IGF-1, KGF, TGF-beta3, Thioredoxin, VEGF, aFGF, FGF-10, copper peptide, acetyl hexapeptide, palmitoyl pentapeptide, CPP, and elm glycoprotein. A composition and method for effectively retarding aging.

Growth Factor, EGF, Elm Glycoprotein, Skin Aging, Hair Growth

Description

Growth factor for the treatment of hair and skin {GROWTH FACTOR FOR HAIR AND SKIN TREATMENT}

1 is a graph showing the proliferation rate of EGF-treated cells.

2 is a graph showing the proliferation rate of AC-treated cells.

3A-3C are photographs showing the comparison of EGF-treated, AC-treated and untreated controls.

This invention claims priority to US Provisional Patent Application No. 60 / 664,722, filed March 23, 2005, which is incorporated herein by reference.

As the human body ages, the production of cytokines decreases. This reduction in cytokines causes wrinkles, hair loss, fat accumulation, dermatitis and other aging-related diseases. In addition, cytokines are closely related to several diseases in the body. Efforts are underway to use cytokines as part of the treatment of these diseases.

Aged skin may have changes in skin color, including reduced thickness of the epidermis and dermis, roughness of the skin surface, enlargement of pores, formation of wrinkles, yellow, bronze, brown spots, capillary dilemma or "Broken vein" and other features.

Recovery of aging or damaged skin tissue is very closely related to cytokine activity. Such cytokines are used in patients by oral or parenteral methods, that is, by injection. However, this method has the disadvantage of providing a large amount of cytokines until the patient exhibits sufficient activity. These methods also require high cost over time.

It may also be possible to replenish substances that promote the production of cytokines. Direct supplementation of cytokines will probably be made by parenteral administration such as oral administration, injection or subcutaneous feeding. However, supplementation of cytokine production-promoting substances, like the supplementation of cytokines, is expensive and requires a lot of time.

Long-term supply of large amounts of cytokines disrupts the patient's entire metabolic process. In addition, the supply of cytokines from the outside is ineffective because it only affects locality due to degradation and low absorption. That's why we've come to expect safer ways to treat aged and lightened skin and to promote hair growth.

In order to solve the above problems, an object of the present invention is to provide a safe method for promoting the growth of hair and the treatment of aged or damaged skin using a variety of growth factors and compositions for the same.

In a first set of exemplary embodiments the invention provides EGF, bFGF, IGF-1, KGF, TGF-β3, TRX, VEGF, TRX, aFGF, FGF-10, copper tripeptide, acetyl hexapeptide, palmitoyl pentapeptide, CPP And a therapeutic method that can effectively delay aging composed of one or more of the elm glycoproteins.

In a second set of exemplary embodiments, the invention provides EGF, bFGF, IGF-1, KGF, TGF-β3, TRX, VEGF, TRX, aFGF, FGF-10, copper tripeptide, acetyl hexapeptide, palmitoyl pentapeptide, CPP And an effective anti-aging composition composed of one or more of the elm glycoproteins.

In a third set of exemplary embodiments, the invention relates to a method of treatment that can effectively delay aging consisting of one or more of bFGF, KGF, IGF-1, SCF, VEGF, aFGF, Noggin, thymosinβ4 and copper tripeptides .

In a fourth set of exemplary embodiments, the present invention relates to a composition capable of effectively treating hair loss consisting of one or more of bFGF, IGF-1 and VEGF.

In a fifth set of exemplary embodiments the present invention relates to a method for effectively treating acne consisting of one or more of EGF, bFGF, TRX, elm glycoprotein, IL-4, IL-10 and SCF.

In a sixth set of exemplary embodiments, the present invention relates to a composition that can effectively treat acne, consisting of one or more of EGF, bFGF, TRX, elm glycoprotein, IL-4, IL-10 and SCF.

In a seventh set of exemplary embodiments this invention relates to a method for effectively treating acne consisting of one or more of EGF, IGF-1, bFGF, elm glycoproteins and copper tripeptides.

In an eighth set of exemplary embodiments, the present invention relates to a composition for effectively treating acne consisting of one or more of EGF, IGF-1, bFGF, elm glycoproteins and copper tripeptides.

In a ninth set of exemplary embodiments this invention relates to a method for treating atopic dermatitis consisting of one or more of EGF, bFGF, TRX, elm glycoprotein, IL-4, IL-10 and SCF.

In a tenth set of exemplary embodiments, the present invention relates to a composition for treating atopic dermatitis consisting of one or more of EGF, bFGF, TRX, elm glycoprotein, IL-4, IL-10 and SCF.

In an eleventh set of exemplary embodiments, the present invention relates to a method for effectively treating psoriasis consisting of one or more of EGF, bFGF, TRX, elm glycoprotein, IL-4, IL-10 and SCF.

In a twelfth set of exemplary embodiments the invention relates to a composition for effectively treating psoriasis consisting of one or more of EGF, bFGF, TRX, Elm glycoprotein, IL-4, IL-10 and SCF.

In a thirteenth set of exemplary embodiments, the present invention is directed to a method for promoting fat metabolism using a composition composed of one or more of IGF-1 and L-carnitine to effectively increase the lipolysis of a patient.

In a fourteenth set of exemplary embodiments, the present invention is directed to a composition that promotes fat metabolism using a composition that effectively increases the lipolysis of a patient composed of one or more of IGF-1 and L-carnitine.

In a fifteenth set of exemplary embodiments this invention relates to a method for effectively treating vitiligo consisting of one or more of bFGF and SCF.

In a sixteenth set of exemplary embodiments this invention relates to a composition for effectively treating vitiligo consisting of one or more of bFGF and SCF.

In a seventeenth set of exemplary embodiments, the present invention relates to a method for effectively reducing UV exposure comprising one or more of EGF, bFGF, IGF-1, TRX, elm glycoprotein and CPP (Caregen Plant Placenta). It is about.

In an eighteenth set of exemplary embodiments, the invention is directed to compositions that effectively reduce UV exposure comprising one or more of EGF, bFGF, IGF-1, TRX, elm glycoproteins and CPP (Caregen Plant Placenta). It is about.

In a nineteenth set of exemplary embodiments this invention relates to a method for effectively treating atopic dermatitis consisting of one or more of EGF, bFGF, TRX and IL-10.

In a twentieth set of exemplary embodiments this invention relates to compositions that effectively treat atopic dermatitis consisting of one or more of EGF, bFGF, TRX and IL-10.

Hereinafter, the present invention will be described in more detail.

Cytokines used to protect skin or hair include epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth Basic fibroblast growth factor (bFGF), thioredoxin-1 (TRX), keratinocyte growth factor (KGF), stem cell factor (SCF), traits Transforming growth factor-beta 3 (TGF-beta 3), interleukin-10 (IL-10), platelet-derived growth factor (PDGF), Vascular endothelial cell growth factor (VEGF), acidic fibroblast growth factor (aFGF), fibroblast growth factor-10 (FGF-10), Interleukin-4 (IL-4), Noggin, T Shin-refers to beta 4 (thymosin-beta 4), and hepatocyte growth factor (hepatocyte growth factor, hereinafter HGF) and so on. These cytokines bind to tyrosine or threonine kinase receptors to activate cells. Peptides used to protect skin or hair include copper tripeptide, acetyl hexa peptide, and palmitoyl pentapeptide.

EGF consists of 53 amino acids and is found in different concentrations in breast milk, saliva, urine, plasma, and other body fluids. EGF stimulates mitosis, cell differentiation, or regeneration in wounded or aged epithelial cells. EGF promotes cell growth and differentiation, plays an important role in embryonic development, and plays an important role in wound healing. EGF promotes the division of fibroblasts that synthesize collagen and elastin, which helps the skin recover. In addition to increasing skin elasticity, promoting wound healing, and anti-aging, the treatment of EGF has various effects.

IGF-1 is structurally similar to insulin consisting of a chain of 7.6 kDa consisting of 70 amino acids and is a polypeptide produced mainly in liver and fibroblasts. This promotes cell growth and development, especially in neurons. IGF-1 is a marker in skin aging, and its aging tends to decrease as the skin ages. The introduction of IGF-1 into the skin increases the synthesis of hyaluronic acid and collagen and restores the skin to a young state. IGF-1 is produced as a result of stimulation of growth hormone, which is secreted, and the increase in the amount of IGF-1 improves insulin action. Treatment of IGF-1 to various tissues, including the skin, has various effects in addition to activities such as increased skin elasticity, wound healing, promotion of anti-aging, hair growth, body fat reduction, and muscle gain.

bFGF is a single chain protein with a molecular weight of 17.3 kDa consisting of 155 amino acids, which is effective for the repair of aged tissues and the healing of wounds and bruises. This promotes wound healing and tissue regeneration. bFGF works with EGF or other growth factors to improve skin elasticity and increase the synthesis of elastin and collagen, which are components of healthy skin. bFGF promotes fibroblast division at the basement membrane in the dermis and increases the synthesis of hyaluronic acid in keratinocytes by interacting with EGF and IGF-1. The combination of bFGF and IGF-1 increases the synthesis of elastin and collagen at the root of the hair cells, thereby controlling the hair cycle to maintain healthy hair and prevent hair loss. bFGF also has the effect of delaying the bleaching of hair. Treatment with bFGF has various effects in addition to increasing skin elasticity, promoting hair growth, promoting wound healing, and promoting anti-aging conditions.

TRX is a 105 amino acid protein with an antioxidant effect that neutralizes free radicals that are critical for skin aging. TRX binds to intracellular transcription factors and prevents aging caused by several DNA factors. The use of TRX has the effect of sun protection, increasing skin elasticity, promoting wound healing, and promoting an anti-aging environment.

KGF is a protein composed of 163 amino acids, which promotes the division of the envelope cells and enables rapid regeneration from various wounds. KGF is a member of the fibroblast growth factor family and affects many cell types. KGF plays an important role in healing cell damage caused by a number of causes, including intercellular adhesion, cell division, and aging. KGF plays an important role in crosslinking between cell generations in the early stages of hair growth. KGF can be used in many places besides increasing skin elasticity, promoting hair growth, and promoting wound healing.

SCF is a 164 amino acid protein found in the keratinocytes of the skin and melanocytes during development. SCF and its receptor c-kit play an important role in the development of melanocytes during development and the depigmentation of hair due to genetic causes. The use of SCF can be used to increase skin elasticity, to treat de-pigmented tissues through the maintenance and production of melanocytes.

TGF is a cytokine that plays an important role in the growth and differentiation of skin cells to keep younger and healthier in the deep skin. For example, through transformation and recovery, old, wounded cells are transformed into healthier, more productive cells. TGF prevents the healing of already wounded cells and the resulting scarring in tissues. It binds to the receptors of EGF, increases the synthesis of basement membrane proteins, and stimulates endothelial cell growth. The use of TGF has several effects besides increasing skin elasticity, promoting hair growth, promoting wound healing, and creating an anti-aging environment.

IL-10 is a protein of molecular weight 18.6 kDa consisting of 160 amino acids. IL-10 modulates the immune response in the form of autocrine and paracrine. It is a biological inducer of immune tolerance through the inhibition of T cells. The use of IL-10 can be used to treat skin inflammation, promote wound healing, atopic dermatitis and relieve psoriasis.

PDGF is a protein of 14.3 kDa consisting of 125 amino acids. PDGF promotes wound healing by stimulating the production of other growth factors associated with the promotion of blood vessel production at the wound site. PDGF also promotes the differentiation of fibroblasts that synthesize collagen to help skin regeneration. The use of PDGF has the benefits of creating an anti-aging environment, promoting hair growth, and increasing skin elasticity.

VEGF is a growth factor that plays an important role in the growth of endothelial cells, especially in angiogenesis. VEGF plays an important role in angiogenesis before hair follicle formation in the hair cycle. By using VEGF, effects such as promoting hair growth and restoring skin elasticity can be seen.

aFGF is an important factor in the differentiation and division of endothelial cells important for angiogenesis. It is a potent extracellular mitotic factor and wound healing promoter for many cells derived from mesodermal and ectoderm cells of the embryo, including keratinocytes, fibroblasts, and vascular endothelial cells of skin-derived epidermal cells. By treating aFGF, the effects of promoting anti-aging conditions, increasing hair growth, and ensuring skin elasticity can be seen.

FGF-10 also promotes wound healing by inducing division and differentiation of human keratinocytes. The function of FGF-10 is similar to that of FGF-7 (KGF). By using FGF-10, the effects of promoting anti-aging conditions, increasing hair growth, and increasing skin elasticity can be seen.

IL-4 promotes the differentiation and division of activated B cells. IL-4 acts like EPO or G-CSF to effect colony differentiation of hematopoietic stem cells and granulocytes, and induces the division of keratinocytes in normal people. The use of IL-4 can be effective in the treatment of psoriasis.

Copper tripeptides increase the activity of metalloproteases in the skin. It also improves the elasticity of the skin and reduces the wrinkles by increasing the biosynthesis of collagen and elastin. Copper tripeptides improve the function of the skin through the production of proteoglycans and glycosaminoglycans, which are components of the extracellular layer, thereby reducing the degree of aging. Copper tripeptides slow aging through the activity of suproixdase dismutase, which is important for skin cell metabolism. Copper tripeptides increase the size of hair follicles, promote hair growth, and inhibit hair loss. By using copper tripeptide, the effects of promoting anti-aging conditions, increasing skin elasticity, preventing hair loss, increasing hair thickness, and promoting wound healing can be seen.

Noggin is important for hair follicle induction. It acts as an inhibitor of BMP2 / 4, which inhibits the onset of the anagen phase, leading to the transition from telogen to anagen. Noggin can be used to promote hair growth.

Thymosin β4 is the first substance isolated from the thymus. This affects the growth, differentiation and division of hair follicle stem cells. Thymosin β4

Promotes hair growth by activating the hair cells of hair follicles. Thymosin β4

By using this, effects such as promotion of hair growth can be seen.

Growth hormone reduces body fat and increases muscle strength and immunity. It is known to reduce stress levels, which are growth hormones. By using growth hormone, it can be seen to promote hair growth, increase skin elasticity, and reduce fat cells.

Acetyl hexapeptide is a botox-like nontoxic peptide. Acetyl hexapeptide has the advantage of no side effects such as allergic reactions caused by Botox. Acetyl Hexapeptide is not toxic to humans and has anti-wrinkle and anti-aging effects. Acetyl hexapeptide is a small molecule that can easily penetrate into muscle tissue and work effectively. Through this process, it can exhibit a short time or skin elasticity. This can prevent wrinkles by affecting the secretion of catecholamines that cause wrinkle formation. Acetyl hexapeptide regulates the formation and safety of the SNARE complex. SNARE complexes formed by acetyl hexapeptides directly affect muscles and affect wrinkle formation. By using acetyl hexapeptide, the effects of promoting anti-aging conditions and increasing skin elasticity can be seen.

Palmitoyl pentapeptides activate skin cells to synthesize collagen and glycosaminoglycans without side effects. Palmitoyl pentapeptides repair skin damage caused by ultraviolet radiation and reduce the depth and number of wrinkles. It generally shows almost twice the activity without the side effects of retinol. It is more stable under normal conditions than retinol. By using palmitoyl pentapeptide, effects such as promotion of anti-aging conditions and increased skin elasticity can be seen.

Elm glycoproteins were isolated from Ulmus Davidiana Nakai. Elm is a deciduous tree that exists throughout Korea. Glycoproteins isolated from the elm tree showed potent antioxidant effects on free oxygen radicals in various oxygen-radical formation experiments.

The cytokines and growth factors mentioned above are applicable to anti-aging, anti-wrinkle, hair loss prevention products, geodegradation products, anti acne products, mesotherapy products, sunscreens, anti-atopic products, and anti-psoriasis products.

Anti-aging, anti-wrinkle products for EGF, bFGF, IGF-1, KGF, TGF-beta3, TRX, VEGF, aFGF, FGHF-10, copper tripeptide, acetyl hexapeptide, palmitoyl pentapeptide, elm Glycoproteins, and plant extracts. EGF and IGF-1 promote epidermal cell growth, and bFGF stimulates collagen synthesis in dermal cells. The function of cytokines and growth factors promotes the regeneration of the cortex, the division of fibroblasts and the reduction of reactive oxygen species (ROS).

As important regulators of wound healing have become known, the beneficial effects of adventitious growth factors on wound healing have been revealed, as well as the demonstration that many growth factors and cytokines have the same in vitro activity.

EGF and IGF-1 in the outer skin promotes cell division. This activity stimulates other cytokines that affect the survival and division of skin cells. bFGF not only increases collagen synthesis but also upregulates the activity of EGF. bFGF also increases the amount of collagen short-circuit to form a tight collagen lattice structure, increasing skin elasticity. IGF-1 acts similar to growth hormone in the outer tissue. IGF-1 affects the formation of blood vessels, bones, muscles and nerves. The introduction of IGF-1 allows the formation of new blood vessels in physically injured tissue with reduced blood vessels. As a result of the formation of new blood vessels, the supply of nutrients and the removal of cell secretions occur efficiently, facilitating cell division.

Products for hair growth and hair loss prevention include bFGF, KGF, IGF-1, SCF, VEGF, copper tripeptides, aFGF, Noggin, thymosin β4, and plant extracts.

Plant extracts include ginkgo biloba extract, licorice extract, mantididootheca extract, mulberry root extract, sewage extract, cypress extract, VF-1, and WKC.

Hair follicles are small but dynamic tissues that synthesize biological fibers called hair. All hair follicles have a cyclic growth cycle consisting of the anagen phase, the catagen phase, and the telogen phase. Although the precise mechanisms are unknown, the regulation of the molecular level of epithelial cells under the influence of mesenchymal tissue is likely to play an important role in terminal division of the follicle base. Recently, some members of growth factors have been reported to be involved in hair differentiation and hair cycle regulation. These polypeptides or proteins are produced in cells by cell growth regulators. They bind to receptors on the cell surface and carry their signals. Hair follicle growth is inhibited by EGF, EGF-2 and TGF-beta, and elevated by near-stimulus growth factors such as KGF, IGF-1, and HGF.

This invention relating to skin and hair protection is directed to normalizing the hair cycle and increasing hair growth. It includes hair loss prevention, collagen and elastin synthesis, nutrition of hair follicles, stimulation of hair growth due to increased hair follicle size, and prevention of hair loss.

Body care products such as lipolysis use EGF, bFGF, IGF-1, KGF, TGF, TRX, VEGF, copper tripeptide, acetyl hexapeptide and palmitoyl pentapeptide.

IGF-1 is a growth hormone that breaks down fats and increases muscles. Growth hormone stimulates the production of IGF-1 and indirectly promotes body growth. IGF-1 is synthesized in the liver and many other tissues in response to growth hormone binding. After release into the blood, IGF-1 targets receptors present in skeletal muscle, bone, and cartilage. This promotes protein synthesis and cell differentiation.

Growth factors and cytokines induce effective lipolysis through the bloodstream, and this action causes a decrease in body fat through slimming massage. These changes increase basal metabolism and inhibit the function of phosphodiesterases. Our bodies have B-receptors that help break down fat faster. This promotes lipolysis by increasing cAMP.

Hormones melt fat and react directly with fatty elements through the adrenoreceptor. These hormones include growth hormone, thyroid hormones, glucagon, and many other hormones. Adrenoreceptors are of type α and β. β-adrenoreceptors act in the body during lipolysis.

Fat burning complexes reduce body fat by burning fat in large amounts and increase energy use and basal metabolism. It also prevents the loss of norepinephrine due to increased body temperature and increased cAMP following body fat breakdown.

The fat burning complex in this invention is expected to regulate the formation of acetyl-CoA-carboxylase, which causes the formation of body fat. It regulates squalene epoxidase, which forms cholesterol, which reduces cholesterol formation. Excess food intake forms glycogen and increases body fat. Glycogen is used to increase blood flow, which helps the body burn fat effectively. Ginkgo leaf extract causes body fat burning through blood circulation. Faster and more effective results can interfere with fat reconstitution and increase muscle mass to increase fat burning and elasticity.

Products for skin conditions and diseases such as acne, atopy, and psoriasis use EGF, bFGF, TRX, elm glycoproteins, IL-4, IL-10, SCF, copper tripeptides, and anti-acne complexes. In particular, the anti-acne complex contains EGF, bFGF, TRX, copper tripeptides, and elm glycoproteins. For psoriasis, IL-10 and elm glycoproteins are used. For atopy use IL-10, TRX, EGF, bFGF. BFGF and SCF are used for anti- vitiligo.

The anti-acne product in this invention consists of three steps. The first stage is the antimicrobial stage due to IgY and nisin. The second step is an anti-inflammatory step that includes elm glycoproteins. This step includes a CG-anti-acne complex that is effective against several bacteria for the prevention of bacterial diseases. The third stage is the treatment and remodeling phase consisting of EGF, bFGF, and copper tripeptides. This third step promotes the synthesis of collagen and elastin, both components of the skin and of the barrier. This anti acne complex includes anti Propionibacterium acnes, anti Staphylococcus epidermidis, anti enterotoxigenic E. coli antibodies.

Raw materials for the anti-aging meso product of the present invention are cytokines: EGF, IGF-1, bFGF, copper peptide, vitamins: B complex, C, H, A, D, E, K, minerals: Ca, Mg, K , Na, amino acids: alanine, arginine, glutamine, lysine, nucleic acids: adenosine cyclic phosphate, cytosine, guanosine, tymine; 7. coenzymes: CoA, Cocarboxylase, NAD, FAD, and reducing agent: include but are not limited to gluthation.

Raw materials for a hair loss prevention embodiment of the present invention are cytokines: IGF-1, bFGF, VEGF; peptide: copper peptide; vitamins: B complex, C, H, A, D, E, K; minerals: Ca, Mg, K, Na; amino acids: alanine, arginine, glutamine, Lysine; nucleic acids: adenosine cyclic phosphate, cytosine, guanosine, thymine; coenzymes include, but are not limited to, CoA, Cocarboxylase, NAD, FAD and reducing agent: gluthation.

Raw materials for the sunscreen product embodiments of the present invention include EGF, bFGF, IGF-1, TRX, CPP, elm glycoprotein, herbal extracts, octyl methoxycinnamate, titanium dioxide, zinc oxide, octyl saliclate It is not.

Raw materials for the anti-atopic product embodiments of the present invention include, but are not limited to, IL-10, TRX, EGF, bFGF. To achieve a Th1 / Th2 cytokine balance that inhibits IL-5 production by dormant T cells and TH0 and TH2 clones.

There is an inhibitory effect on the expression of molecules that are stimulating to APC. Epithelial cell growth is caused by the promotion of cell division. Collagen and elastin synthesis is promoted by increasing fibroblasts, which balance the TH1 and create an immune condition that prevents the development of atopy.

Raw materials for the anti-psoriasis product embodiment of the present invention include IL-10, and elm glycoprotein, but is not limited to these raw materials. This balances the Th1 and Th2 types and prevents the production of Interferon gamma in Th1 cells, which decreases MHC expression and pro-inflamentory cytokine production in monocytes and macrophages.

In the examples these products will be formulated in lotions, creams or powders. Lotions may be formulated in water-soluble or emulsified form and include stabilizers, emulsifiers, diffusion accelerators, flocculants, thickeners, colorants and the like.

The powder will be formulated with the help of appropriate raw materials such as talc, lactose and starch. Ointments, creams and gels contain paraffin, starch, tragacanth rubber, cellulose derivatives, polyethylene, glycols, silicones, talc and zinc oxide. The composition will include emollients, lubricants, emulsifiers, thickeners, wetting agents, preservatives, antifungal agents, fragrances.

In an embodiment the cytokines and growth factors may be put into creams or lotions as microspheres. An example of adding microspheres to creams or lotions is disclosed in list patent numbers here.

In an embodiment, the cytokine and growth factor may be put into a cream or lotion as nanospherical particles. Examples of adding nanospherical particles to creams or lotions are disclosed in U.S. Patent No .: 5,554,374 and U.S. Patent No .: 6,203,802.

Topical pharmaceutical formulations may include preservatives or bacterial growth inhibitors such as methyl hydroxybenzoate, propyl hydroxybenzoate and benzalkonium chloride.

Compositions in this invention are, for example, water or alcohols; Humectants, including glycerin; buffer components, including citric acid and sodium citrate; viscosity increasing agents including carbomer gelling agents, gum derivatives; And preservatives containing methylparaben, propylparaben, and phenoxyethanol; emulsifiers including polysorbitate 80, glyceryl distearate, POE 10 stearyl ether, ceateareth 20, stearyl alcohol, ceteareth 20 and cetearyl alcohol; conditioning agents such as octyl hydroxystearate; emollients such as cholesterol NF, petrolatum, mineral oils and esters, isopropyl myristate, isopropyl palmitate, 1-decene polymer (hydrogenated), and mineral oils such as C.sub.12 -C.sub.15 alcohol benzoates; thicknesses such as polyacrylamide, C.sub.13-C.sub.14 isoparafin, and laureth-7; antioxidants such as ascorbic acid, (BHT), tocopheryl acetate; Sunscreens; UV absorbers; Spices; It is composed of dyes, but not limited to these raw materials.

These compositions can be configured as creams, gels, or solutions, and also as lotions. Multi-lamellar vesicles, liposomes, nanospheres, microsponges, or other combinations can be constructed using known methods.

This invention is possible with the composition of a cosmetic or a medicament which can be applied to the upper layer of the skin by local treatment.

It is well known in cosmetic and pharmaceutical formulations for the supply of dermal oils, including the active ingredient. These oily ingredients are often used as emulsions in the form of water-in-oil or oil-in-water. These oily ingredients act on the surface of the skin, but also act on the outer layer to help cosmetic or drug activity pass through the stratum corneum and absorb it well.

In addition, there are nano-particles. It refers to colloidal grains composed of polymeric materials with sizes ranging from 10 to 1,000 nm containing active ingredients (J. KREUTER, J. MICROENCAPSULATION 1988, Vol. 5, pages 115-127). Nanoparticles can be divided into nanospheres (nano-sphere) and nanocapsule (nano-capsule). Nanosphere refers to a porous solid polymer containing an active ingredient, nanocapsule refers to a form in which the active fingerprint is wrapped with a polymer membrane. For the remainder of the description and in the claims, the scope of the term "nanoparticles" will be limited to the nanocapsules defined strictly above. Biodegradable materials used in the manufacture of nanoparticles will make the nanoparticles available for therapeutic purposes. Such biodegradable materials may be cyanoacrylates, and in particular polyalkyl cyanoacrylates; EP-B-0,007,895 and EP-B-0,064,967 describe methods for making nanoparticles from cyanoacrylates.

The use of nanoparticles that can be degraded into harmless substances by microorganisms that encapsulate the biologically active substance is thus beneficial for many active ingredients and health such as cell division inhibitors or anti-tumor substances, antibiotics, hormones, insulin, heparin or biological agents. It is possible for elements of proteins, antigens or viruses, bacteria or cells to help maintain. This has already been applied for the delivery of active substances to oral administration, subcutaneous, intradermal, intramuscular, intravascular and eye (see EP-B-0,007,895, EP-B-0,064,967, FR-B-2,604,903, DE-A). -3,722,837, DE-A-3,341,001 and FR-B-2,304,326).

In FR-A-2,515,960, an oily or active ingredient protected by nanoparticles of cyanoacrylate has been reported for oral administration, subcutaneous, intradermal, intramuscular, and intravascular distribution. In addition to this, the use of nanoparticles has been described in terms of keeping perfumes alive for a long time, allowing the perfume odor to last longer after application than in the case where perfume is applied to the skin without encapsulation; Since it's encapsulated, the smell of perfume is long lasting. In addition, in this situation, the nanoparticles will allow the perfume to penetrate independently of the skin layer rather than directly on the skin. This topical treatment cannot provide any information about the possibility that nanoparticles will biodegrade under the outer layer through the stratum corneum; On the other hand, it tells us that nanoparticles remain on the skin while the perfume is released.

This topical treatment shows that the composition of the biodegradable nanoparticles containing the active ingredient is particularly effective in cosmetics or pharmaceuticals.

Improvements to enhance the effectiveness of oily cosmetics or drugs contained in nanoparticles cannot be identified; It is not clear whether the nanoparticles pass through the stratum corneum or biodegrade under the envelope rather than the unencapsulated oil phase in the form of a water-in-oil or oil-in-water emulsion. It is known to introduce into various tissues, in particular the biodegradation of nanoparticles upon injection. However, it is well known that different tissues have different compositions and contain different enzymes; ; In particular, when nanoparticles are introduced through injection into the connective tissue, dermis, and deep layers of the skin, it is well known that they have very different biochemical configurations under the outer cortex. (British Journal of Dermatology (1976) 94, 443).

Therefore, nanoparticles do not have the expected effect by allowing large amounts to penetrate the stratum corneum, but on the other hand secreting the active ingredient very quickly from the outer layer.

According to this invention, the active ingredient produced and processed nanoparticles surprisingly found that the composition reacts immediately. Delayed effects have been reported in topical treatments using the perfume composition mentioned in FR-A-2,515,960, and only delayed effects have been reported instead of other expected effects. This invention therefore proposes a composition for unexpected properties. In addition, these properties are more suitable for topical treatment compared to in vitro studies on transdermal absorption.

The subject of the present invention is to treat a cosmetic or pharmaceutical composition on top of the outer skin layer in a method local to the skin in a suitable vesicle with biodegradable polymeric nanoparticles comprising at least one active ingredient in an active or inactive oily ingredient from cosmetic or pharmaceutical activity. It is about.

Nanoparticles are referred to as 10 to 1,000nm in size, and are referred to as the size of 50 to 500nm by segmentation.

The weight of the nanoparticles uses a weight of at least 0.1 to 20%, preferably 0.5 to 5%, of the total amount of the composition per one active ingredient.

The polymer composition of the biodegradable nanoparticles is C.sub.2 -C.sub.12, and especially C.sub.2 -C.sub.6 and alkyl cyanoacrylate. Alkyl radicals consist of ethyl, n-butyl, hexyl, isobutyl and isohexyl radicals. Biodegradable polymers are polymers of poly-L-lactides, poly-DL-lactides, polyglycolides, polycaprolactones, 3-hydroxybutyric acid, and co-polymers such as copoly (DL-lactides / glycolides) and copoly (glycolides / caprocolatones). .

The use of nanoparticles obtained from poly-L-lactides, poly-DL-lactides and copolys (DL-lactides / glycolides) is more advantageous due to the enzymatic or chemical biodegradation products of these nanoparticles in cosmetic use; lactic acid is used as a humectant and plasticizer; And glycolic acid has depigmentation and biostimulation properties.

The active ingredients formed from oil phase are α-tocopherol, α-tocopherol acetate, triglycerides rich in linoleic and / or linolenic acid (s), pentaerythritol tetra (2-ethylhexanoate), clofibrate, tocopherol linoleate, fish oil, hazelnut oil, bisabolol, farnesol It is optionally used in the group of farnesyl acetate, ethyl linoleate and ethylhexyl para-methoxycinnamate.

Inert carrier oils are optionally used from the group consisting of triglycerides which are particularly simple or modified by oxyethylenation, volatile silicone oils and mixtures.

The method of incorporating the active ingredient of cosmetic or therapeutic activity into an active or inactive oil has been obtained according to the composition of the invention. These active ingredients are plasticizers, humectants, free radical inhibitors, anti-inflammatory agents, vitamins, depigmentants, anti-acne agents, anti-seborrheic dermatitis, keratinizers, slimming agents, skin colorants, and sunscreens, especially linoleic acid, retinol, retinoic acid, antioxidants such as ascorbic acid alkyl esters, polyunsaturated fatty acids, nicotinic esters, tocopherol nicotinate, unsaponifiables of rice, ceramides such as soybean or glycolic acid, hydroxy acids, selenium derivatives, β-carotene, γ-orizanol and stearyl glycerate.

The active ingredient is probably a lipophilic active ingredient in an oily solution. But it may take the form of dispersion, suspension or emulsification.

The weight ratio of biodegradable polymer to active oil phase in the nanoparticles will probably be between 0.05 and 0.5, and especially around 0.2.

The composition according to the invention is homogeneous consisting of physiological solutions, lotions, aqueous solutions, aqueous-alcohol or oily gels, or ionic or non-ionic lipids with or without water-in-oil or oil-in-water emulsions or oily phases. Aqueous dispersions of lipid lipid vesicles.

Their use in constituting physiological solutions is particularly advantageous: in fact, this type of product requires enormous emulsifiers when it is desired to introduce an active ingredient in an unencapsulated oily phase, and the emulsifiers irritate the skin. It is well known to produce and incompatible with all active ingredients.

The nanoparticles can contain fats, petrolatum, preservatives, thickening agents, colorants, and perfumes that can be used in cosmetics or pharmaceuticals.

Polymers of (C.sub.2 -C.sub.12) alkyl cyanoacrylic acid are used to obtain nanoparticles. The polymerization of the microemulsion of oil in an aqueous-alcohol medium is carried out as described in FR-A-2,515,960 by injecting onto an aqueous solution containing a mixture of surfactants, oils to be encapsulated. At least one (C.sub.2 -C.sub.12) alkyl cyanoacrylic acid and at least one solvent comprise one surfactant capable of evaporating the solvent or selectively concentrating the aqueous phase diffusion of the obtained nanoparticles. can do. The solvent used is ethanol, propanol, isopropanol or mixtures of these alcohols, or optional acetone: it optionally comprises one surfactant.

European Patent No. It is possible to use the process to produce the nanoparticles depicted in 0,274,961. In this case nanoparticles are obtained by precipitation of a polymer around the diffusion of oil droplets by injecting onto a surfactant, an aqueous solution comprising a mixture of oils for encapsulation, and a solvent comprising at least one surfactant.

Other processes will also be used. The surfactant optionally used in the preparation consists of at least one nonionic surfactant, especially selected from condensates of glycol, ethylene oxide and propylene oxide. Or at least one ionic surfactant taken from a phospholipid group, such as lecithin or a mixture of at least one surfactant of these two categories. These surfactants promote the formation of microemulsions of oil and prevent the adhesion of nanoparticles in the reaction mixture. On the other hand, the mass ratio of the material constituting the nanoparticles mixed with the surfactant used on the one hand and the active material on the other hand is between 0.01 and 0.5. 0.2 is the preferred ratio.

Surfactants used during the manufacture of nanoparticles can form endoplasmic reticulum consisting of lipid lamellae, which encapsulates enclosed spaces. The surfactants mentioned behave in fundamentally different ways depending on whether they are used in aqueous or solvent phase. If the surfactant is in aqueous solution, it forms at least part of the endoplasmic reticulum. If the surfactant is in the solvent, it tends to form one or more lipid lamellae consisting of a molecular double layer around the polymer membrane of each nanoparticle.

In the case of the oil to be encapsulated, it is a self-emulsifying oil selected from oxidized triglycerides. It is not necessary to use surfactants.

Aqueous diffusion of nanoparticles will be used. It can also be freeze dried in the presence of additives that inhibit agglomeration such as silica, sugars, salts, proteins, peptides and amino acids. Desiccant has the advantage that a number of cosmetic ingredients can be prepared. If the nanoparticles are covered with at least one lipid lamellae composed of at least one surfactant capable of forming endoplasmic reticulum, according to the invention the ingredients may have good cosmetic properties. These covered nanoparticles can constitute only one part of the nanoparticles in the composition.

The examples given below will help to understand the invention.

Test Example 1

HACAT cells, which are human keratinocytes, are seeded in 96 well plates and starvated for one day after incubation in DMEM medium containing 10% FBS for one day. After starvation, various concentrations of EGF are added to the free medium without plasma and treated with cells. Referring to FIG. 1, it can be confirmed that EGF-treated cells divide more than untreated cells as measured by MTT assay. ED ₅₀ is nearly 300 pg / ml.

Test Example 2

HACAT cells, which are human keratinocytes, are seeded in 96 well plates and starvated for one day after incubation in DMEM medium containing 10% FBS for one day. After starvation, various concentrations of anti-aging cytokine mixtures (eg mixtures of EGF, bFGF, IGF-1, and TRX) were added to free medium without plasma, and then cultured for 3 days. Referring to FIG. 2, it can be confirmed that the cells divided by the anti-aging cytokine mixture treated cells were more divided than the untreated cells as measured by MTT assay. The ED ₅₀ of the anti-aging cytokine mixture was nearly 90 pg / ml, showing better activity than when using EGF alone.

This enhanced activity is indicated in FIG. 3. FIG. 3A shows untreated cells, FIG. 3B depicts cells treated with 0.5ng / ml EGF and 0.5ng / ml anti-aging cytokine mixture.

Test Example 3

Anti-aging cytokine mixtures consisting of EGF, bFGF, IGF-1, and TRX were prepared as nanocapsules using phosphatidylcholine, cholesterol, and sodium oleate and used for anti-aging creams and skin treatments.

Test Example 4

A cream containing an anti-aging cytokine mixture was applied to the face for 20 weeks, for 20 women over 30, with 0.2 g each twice daily for 6 weeks. The silicone solution was then used to scoop up a copy of the wrinkles. Changes in skin wrinkles were calculated by measuring copies using a Skin Visiometer (SV400 manufactured by Courage-Khazaka Electronics GmbH, Germany). Then, the CCD camera was used to analyze the three-dimensional image of the copy. Skin wrinkle improvement was calculated using the following formula to calculate the average depth of wrinkles.

Table 2 is based on the comparison of 10 control and 10 treatment examples. In the treatment group, wrinkle depth decreased by 0.06 mm to 0.09 mm. No decrease in wrinkle depth was observed in the control group.

Test Example 5

Sixty women in their thirties were organized into three groups (# 1, # 2, control group), respectively, and the improvement in skin wrinkles was measured. An anti-aging cytokine mixture cream was applied to the face 0.2 g each twice a day. Each group was divided into 20 groups and treated on both sides of the face twice a day for 3 months, and the change in wrinkles of the same site where the wrinkles were first measured twice a day for 3 months was measured.

Skin measurements were taken in a space with 40% humidity of 24 degrees Celsius. Then a silicone solution was used to scoop up a copy of the wrinkles. Copies were observed using a Skin Visiometer (SV400 manufactured by Courage-Khazaka Electronics GmbH, Germany) to observe the depth and change of wrinkles. Images of the copy were taken and analyzed using a charge coupled device (CCD) camera equipped with a video sensor, and the average values of wrinkle improvement are summarized in Table 3 below.

In this case, the control group had a decrease in depth of 0.03 to 0.078 mm (average 0.05 mm) and the treatment group 1 decreased 0.121 to 0.153 mm (average 0.139 mm) within the effective statistical range (P <0.01). Within the effective statistical range (P <0.01), the treatment group 2 confirmed the degree of wrinkle improvement of 0.13 3 to 0.163 mm (average: 0.145 mm).

Test Example 6

Glycoprotein extracted from the elm tree was confirmed by SDS-polyacrylamide gel electrophoresis after separation. Elm glycoproteins showed strong activity in removing oxygen free radicals. In order to investigate the apoptosis inhibitory effect of the elm tree glycoprotein, we investigated the activity of protein kinase C alpha, the DNA binding activity of nuclear factor-kappa B, the production of nitric oxide, western blot analysis and electrophoretic mobility shift. Apoptosis was examined in NIH / 3T3 cells stimulated by 12-Otetradecanoylphorbol 13-acetate (TPA) using assays) and NO analysis. Experimental results showed that 100 microg / ml elm glycoprotein inhibited apoptosis in NIH / 3T3 cells promoted by protein kinase C alpha translocation, NF-kappa B DNA binding activity, NO production and TPA (61.68 ng / ml). Have Elm glycoproteins could not modulate the DNA binding activity of AP-1. However, elm glycoproteins, natural antioxidants, are potential regulators of apoptosis signaling processes in NIH / 3T3 cells.

Other embodiments

The invention also provides methods and compositions for treating hair loss with bFGF, IGF-1, and VEGF. It also provides methods and compositions for treating acne with EGF, IGF-1, IgY, and Nicin. In addition, methods and compositions for treating psoriasis with IL-10 are provided.

This invention includes, for example, anti-atopic treatment methods using IL-10 and TRX. In the above concept, the present invention provides a method and composition of UV protection using EGF and TRX.

In order to apply this invention theoretically and practically, figures and examples are described in detail. The specific compositions and processes of this invention are merely illustrative of particular examples to date. However, there will be a later verification in the description and examples of the claims. While some of the examples and explanations provide some conclusions as to how this invention will work, the inventors will not be constrained only to the results and actions to date, but will present possible explanations.

It is contemplated that certain items of the present invention are inclusive or restrictive of the following. And many alternatives, modifications, and variations of the invention may be expressed in conventional techniques in view of the foregoing examples and detailed description. Therefore, it is intended that the present invention cover all such alternatives, modifications, and variations within the scope of the following claims.

REFERENCES CITED

Throughout this application various publications have been referenced. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains.

References:

Pretolani M. Interleukin-10: an anti-inflammatory cytokine with therapeutic potential. Clin. Exp. Allergy 29: 1164-1171 (1999).

Sahni A., et al. (2003) J. Thromb. Haemost. 1: 1304-1310.

Bond JJ., Et al. (1998) Acta Derm. Venerol. 78: 337-342.

Igarashi M., et al. (1998) J. Biol. Chem. 273: 13230-13235.

Soler P. M., et al. (1999) Wound Repair Regen. 7: 172-178.

Woelfle J., et al. (2005) Pediatr. Nephrol. 20: 295-302.

Lee S.J., et al. (2004) Toxicol Lett. Jan 15; 146 (2): 159-74

As described above, according to the composition and method according to the present invention, it is possible to delay skin aging and to obtain excellent effects on hair loss, acne, atopic dermatitis, psoriasis, fat metabolism, vitiligo, and sun protection. do.

Claims (46)

delete delete delete delete delete delete delete delete delete delete delete delete delete delete A composition for delaying skin aging comprising epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1) and thioredoxin (TRX). delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete

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