WO2022265603A1 - Mesoporous dermal formulation with olive oil - Google Patents
Mesoporous dermal formulation with olive oil Download PDFInfo
- Publication number
- WO2022265603A1 WO2022265603A1 PCT/TR2022/050540 TR2022050540W WO2022265603A1 WO 2022265603 A1 WO2022265603 A1 WO 2022265603A1 TR 2022050540 W TR2022050540 W TR 2022050540W WO 2022265603 A1 WO2022265603 A1 WO 2022265603A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- skin
- preparation
- collagen
- polar active
- polyoxyethylene sorbitan
- Prior art date
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- 239000004006 olive oil Substances 0.000 title claims abstract description 18
- 235000008390 olive oil Nutrition 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title abstract description 15
- 230000002500 effect on skin Effects 0.000 title description 4
- 238000009472 formulation Methods 0.000 title description 2
- 239000013543 active substance Substances 0.000 claims abstract description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000126 substance Substances 0.000 claims abstract description 15
- 238000011065 in-situ storage Methods 0.000 claims abstract description 10
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 7
- 102000008186 Collagen Human genes 0.000 claims description 36
- 108010035532 Collagen Proteins 0.000 claims description 36
- 229920001436 collagen Polymers 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- 229960005188 collagen Drugs 0.000 claims description 31
- 229920002674 hyaluronan Polymers 0.000 claims description 23
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 22
- 229960003160 hyaluronic acid Drugs 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 19
- -1 silane compound Chemical class 0.000 claims description 8
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 6
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 4
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 4
- 239000004147 Sorbitan trioleate Substances 0.000 claims description 4
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
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- 235000019337 sorbitan trioleate Nutrition 0.000 claims description 4
- 229960000391 sorbitan trioleate Drugs 0.000 claims description 4
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 claims description 4
- 108010024636 Glutathione Proteins 0.000 claims description 3
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- 229940109850 royal jelly Drugs 0.000 claims description 3
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims description 2
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims description 2
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- 239000003240 coconut oil Substances 0.000 claims description 2
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- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims description 2
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims description 2
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 2
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
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- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 2
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- 241001424688 Enceliopsis Species 0.000 description 2
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 2
- 240000007817 Olea europaea Species 0.000 description 2
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- 230000000975 bioactive effect Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 2
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- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 2
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- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
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- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
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- 241000207836 Olea <angiosperm> Species 0.000 description 1
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- 235000010443 alginic acid Nutrition 0.000 description 1
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- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
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- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/25—Silicon; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/0279—Porous; Hollow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
- A61K8/585—Organosilicon compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/007—Preparations for dry skin
Definitions
- the present invention relates to dermal mixtures that provide long-term controlled subcutaneous release of polar and non-polar active substances, which slow down the aging of the skin against various internal and external factors, without any external factor or intervention by creating a barrier on the skin surface thanks to the entrapment of said active substances in mesoporous silica particles (MSP) synthesized in-situ.
- MSP mesoporous silica particles
- a long-term barrier is formed on the epidermis surface, thus preventing the skin from losing water, and moreover, ensuring the controlled release of components that are vital for the skin from said pores where they are entrapped, and the elimination of deficiencies such as water, oil, collagen, vitamins, etc. that the skin needs.
- suitable conditions are created for the skin to stay younger for a longer period of time and delay aging.
- Human skin is the uppermost layer which covers the human body and has multiple functions, and is a complex organ affected by various internal and external factors. Changes in all these factors affect the appearance of the skin. The clean, smooth, flexible and soft appearance of the skin is of great aesthetic importance.
- CN102309749A a combination of 8-15% collagen protein, 0.5-4% hyaluronic acid, 10-20% olive oil, 10-20% almond oil and others (various oils and petroleum jelly) is used for the purpose of developing a hand and foot cream.
- WO2017133038A1 8-10% lamb placenta extract, 45-60% pigskin collagen, 10-12% alginate, 5-8% olive oil-honey mixture are combined with water for developing an antiaging cream and moisturizer.
- olive oil is transesterified to accelerate the absorption of dermatological active substance through the skin.
- Caffeine, hyaluronic acid, collagen and antioxidants are used as dermatological active ingredients.
- the skin product is prepared by emulsifying the collage peptides, which are obtained by breaking up the fish skin, in olive oil.
- CN101721343A 1-10% deep sea skin collagen and 5-10% olive oil (or jojoba oil) are used as active ingredients for developing a face mask product.
- CN104548190A 10-25% collagen protein, 10-25% collagen tripeptide, 10-25% hyaluronic acid, 8-20% olive oil and other oils, plant extracts and vitamins are combined as a skin cream especially for breast enlargement.
- one or more of the components required for moisturizing and repairing the skin are tried to be applied directly or in combination to the skin surface.
- this application taking into consideration the factors such as the rate of absorption by the skin and the duration of permanence on the skin surface, it is a known fact that the effectiveness of the product decreases shortly after the application and the skin regains its old, dry and lifeless appearance in a short time. Therefore, the desired effect cannot be achieved sufficiently.
- products with high oil content such as petroleum jelly have been used to create a barrier on the skin, and it has been observed that said solutions are not sufficient in terms of user satisfaction and delaying skin aging, since they form a very thick, oily layer and do not have an additional function other than barrier formation.
- MSP mesoporous silica particles
- the mixture of the present invention By means of the mixture of the present invention, it is aimed to delay aging by repairing skin and preventing wrinkles and sagging, and heal various skin wounds in the field of dermocosmetics. For this purpose, it is aimed to develop a cream composition with olive oil for face, neck, hands, feet and body.
- the cream mixture of the present invention comprises the extraction of at least one polar active substance and at least one non-polar active substance from silane compounds and the entrapment, with the help of an emulsifier, of said substances in mesoporous silica particles (MSP), which are produced in-situ.
- MSP mesoporous silica particles
- Another aim of the present invention is the formation of a protective film layer on the skin by means of the MSPs and the long-term, controlled release on the skin by said layer without any external factors or stimuli.
- Another aim of the present invention is to eliminate skin dryness by preventing the skin from losing moisture thanks to the formed film acting as a barrier on the epidermis.
- the human skin is an intelligent barrier composed of heterogeneous layers, which protects the body against various physical, chemical and microbiological factors, which prevents the loss of water and other fluids from the body, which is also permeable to substances applied for treatment, care and healing, and which acts as a barrier between the body and the outside world.
- the skin is composed of three main layers. These layers are hypodermis, dermis and epidermis from bottom to top, and their thicknesses vary at different parts of the body.
- the dermis is the layer that makes the skin elastic and absorbs the substances applied to the skin.
- Collagen and elastin fibers are present in the dermis layer of the skin.
- Collagen and elastin are protein- structured fibers that make the skin elastic and tense. In case of any change in shape, collagen and elastin enable the skin to return to its original shape.
- the epidermis which is the thinnest layer of the skin, is multi-layered, consisting of living and dead cells that renew themselves continuously throughout life, where the renewal process slows down with aging.
- the uppermost layer of the epidermis forms the upper surface of the skin and acts as a barrier.
- This layer consists of natural moisturizing factor and high concentrations of lipid ceramides.
- ceramides are very important for a healthy skin. Ceramides form a barrier that prevents the skin from becoming dehydrated. The decrease in ceramides causes the water to evaporate rapidly and the skin to become dry. Studies show that the amount of ceramide decreases in dry skin and in the elderly and that the lipid composition of the uppermost layer of the epidermis deteriorates in dry skin that occurs in winter and especially a decrease in the ceramide amount is encountered.
- Water is a vital substance for the skin, and the flexible and healthy appearance of the skin is directly proportional to its water holding capacity, and it is known that when there is not enough water in the environment, the skin dries out, loses its elasticity and cracks easily.
- Water provides softness and flexibility for the uppermost layer of the epidermis. Said water content in the uppermost layers of the epidermis is rapidly hydrated and dehydrated due to environmental factors.
- One of the most important functions of the epidermis is to act as a barrier to prevent the water in the living cells underneath from being lost by evaporation. Similar to the diffusion of water from the outside to the skin, there is also the diffusion of water from the lower layers of the skin to the upper layers. Water evaporates from a healthy skin at rates that vary from person to person.
- the diffusion rate of water from the living epidermis to the dead epidermis is not sufficient for dry skin to become elastic and soft again. Supplementing moisture from the outside is not very effective due to evaporation as long as the water is not retained in the uppermost layer of the epidermis.
- the last layer of the epidermis is an important layer that prevents water loss from the skin, its protective feature decreases due to various external factors such as aging, wind, hot or cold weather, excessive skin cleaning with soap or contact with organic solvents.
- aging which is caused by natural or environmental factors, the skin dries out by losing its moisture.
- a skin which is cosmetically old, assumes a dry, inelastic, lifeless appearance with visible wrinkles. From a cosmetic point of view, the reduction of epidermal lipids in the skin prevents the evaporation of water.
- Skin aging is often dependent on age, sunlight, and other factors. The most significant age- related decrease occurs in the natural moisturizing factors of the skin, and this decrease increases age-related skin deterioration.
- the skin exposed to the sun prematurely ages due to UV rays.
- the surface of the skin has a wavy structure during the youth, and thanks to this structure, reflects sunrays and easily resists the external effects.
- the skin surface thickens, hardens and dries, and the ideal wavy structure of the skin is lost.
- the skin assumes a pale and tired appearance.
- the upper layers of the skin lose their integrity.
- moisturizers in skin diseases with such dry skin symptoms is of great importance in terms of treatment effectiveness.
- the regular and correct use of moisturizers may also decrease the amount of steroids that should be used.
- Moisturizers are important in regulating the epidermal barrier and epidermal water content, and in giving the skin a smooth and healthy appearance. Moisturizers increase the water retention capacity of the skin thanks to their covering and water absorbing effects.
- Olive oil obtained from olive fruit is one of the products with superior properties. All the beneficial minerals and vitamins found in olives are also present in olive oil. Natural olive oil can be used for cleaning body, hair and face, and as a cream for moisturizing similar areas. Naturally, olive oil products provide moisture balance of the skin, and are known to support treatments against psoriasis, fungal diseases, skin chafing and other skin diseases. In addition to all these features of dermocosmetics obtained from olive oil, by adding hyaluronic acid and collagen suitable for the structure of the product, deep moisture, tension and elasticity, softness and freshness are provided in the skin, and effective results can be obtained in reducing wrinkles and ensuring facial rejuvenation.
- Hyaluronic acid also known as hyaluronan, is a natural polysaccharide commonly found in the human body with the highest concentrations present in the eyes and joints. Hyaluronic acid is frequently used as one of various cosmetic product ingredients. When products containing hyaluronic acid (gels, creams, facial fillers, lotion, serum and implants, etc.) are examined comprehensively, it is concluded that they have remarkable anti-wrinkle properties. In the literature, it has been reported that hyaluronic acid has important contributions to the cosmetic and nutritional cosmetic efficacy for skin rejuvenation. Studies have shown that if hyaluronic acid has a low molecular weight, it becomes easier to pass through the skin.
- Collagen is abundant in the skin. With aging, collagen loss occurs in the inner layers of the skin, the skin loses its elasticity and becomes vulnerable to damage. Wrinkles begin to form on the skin that loses its elasticity. The skin gradually assumes an aged appearance. By supplementing collagen, the elasticity of the skin increases and the moisture balance of the skin improves.
- Collagen can be obtained from sources such as cattle or pigs, as well as from marine sources. Although there are various types of collagen, Type 1 collagen is the most abundant collagen type in the body and is found in the skin, organs and tendons. Collagen provides the elasticity of the skin and helps the healing of wounds, and products containing collagen are used to support medical treatment such as hair loss and nail breakage. The type and source of collagen, its molecular weight, and solubility are the main factors affecting the properties of collagen in usage areas. Collagen, which is preferred to be used in the mixture of the present invention, is collagen with a low molecular weight, especially obtained from marine sources in order to increase absorption.
- hyaluronic acid and collagen combinations with appropriate type and molecular weight have a synergistic effect in increasing skin tension and elasticity, reducing wrinkles and rejuvenating the skin.
- hyaluronic acid and collagen with a suitable molecular weight for skin penetration in cosmetic products and homogeneous distribution and stability thereof in the dermocosmetic product are very important in achieving the expected effective result.
- mesoporous silica is highly preferred.
- MSP Mesoporous silica particles
- MSP Mesoporous silica particles
- mesoporous silica particles are formed with the in-situ synthesis method by being homogeneously obtained in the reaction medium as a result of hydrolysis condensation of silicon alkoxides from the alkoxysilanes, that is, at the molecular level.
- silica particles are not synthesized by the in-situ synthesis method, but ready-made silica particles are used. Therefore, only an active substance with a uniform polarity can be encapsulated.
- the present invention relates to a dermocosmetic preparation formed by entrapping polar and non-polar active substances in mesoporous silica particles synthesized in situ by hydrolysis condensation of the silane compound, comprising at least one polar active substance, at least one non-polar active substance, at least one emulsifier, and at least one silane compound, with the aim of forming a film on human skin, which can release for a long time without external factors or intervention, to prevent water loss.
- the polar active substance in the dermocosmetic preparation of the present invention can be one or more substances selected from the group consisting of collagen, hyaluronic acid, glutathione, and royal jelly, and is especially preferred to be collagen.
- hyaluronic acid a hyaluronic acid with low molecular weight is preferred.
- a hyaluronic acid with low molecular weight and collagen can also be preferred to be used together.
- the non-polar active substance mentioned in the preparation of the present invention can be a substance selected from the group consisting of olive oil, shea butter, cocoabutter, and coconut oil, and is especially preferred to be olive oil.
- the emulsifier mentioned in the preparation of the present invention can be a substance selected from the group consisting of Polyoxyethylene sorbitan trioleate, Polyoxyethylene sorbitan monooleate, Polyoxyethylene sorbitan monostearate, Polyoxyethylene sorbitan monopalmitate, Polyoxyethylene sorbitan monolaurate, and is especially preferred to be polyoxyethylene sorbitan trioleate.
- the silane compound mentioned in the preparation of the present invention can be a compound containing tetramethoxysilane, tetraethoxysilane, and is especially preferred to be tetramethoxy sil ane .
- hyaluronic acid is not used as the polar active substance mentioned in the preparation of the present invention
- at least one substance selected from the group consisting of collagen, glutathione and royal jelly can be used.
- the collagen used in the preparation of the present invention is collagen derived from marine sources.
- propolis, biotin, vitamins C and E can also be used in double or triple combinations.
- the dermacosmetic preparation of the present invention is especially in the form of cream and acts as a barrier by forming a film on the skin. By preventing water loss, it protects the skin against external effects and is characterized by a long-term controlled release especially from the skin to the subcutaneous tissue.
Abstract
By means of the mixture of the present invention, it is aimed to delay aging by repairing skin and preventing wrinkles and sagging, and heal various skin wounds in the field of dermocosmetics. For this purpose, it is aimed to develop a cream composition with olive oil for face, neck, hands, feet and body. The cream mixture of the present invention comprises the extraction of at least one polar active substance and at least one non-polar active substance from silane compounds and the entrapment, with the help of an emulsifier, of said substances in mesoporous silica particles (MSP), which are produced in-situ.
Description
MESOPOROUS DERMAL FORMULATION WITH OLIVE OIL
TECHNICAL FIELD
The present invention relates to dermal mixtures that provide long-term controlled subcutaneous release of polar and non-polar active substances, which slow down the aging of the skin against various internal and external factors, without any external factor or intervention by creating a barrier on the skin surface thanks to the entrapment of said active substances in mesoporous silica particles (MSP) synthesized in-situ. In the mixture of the present invention, by means of the MSPs, a long-term barrier is formed on the epidermis surface, thus preventing the skin from losing water, and moreover, ensuring the controlled release of components that are vital for the skin from said pores where they are entrapped, and the elimination of deficiencies such as water, oil, collagen, vitamins, etc. that the skin needs. Thus, by means of this effect, which is made permanent on the skin surface contrary to classical methods, suitable conditions are created for the skin to stay younger for a longer period of time and delay aging.
PRIOR ART
Human skin is the uppermost layer which covers the human body and has multiple functions, and is a complex organ affected by various internal and external factors. Changes in all these factors affect the appearance of the skin. The clean, smooth, flexible and soft appearance of the skin is of great aesthetic importance.
The needs of the skin for a healthy and youthful appearance should be considered in many respects. Although proper and balanced nutrition, adequate water intake, regular and quality sleep, and exercise are important factors for skin health, undesirable conditions such as skin dryness, aging, wrinkles and sagging occur inevitably due to time and environmental factors. Internal factors such as aging, hormonal changes, stress, and external factors such as industrial nutrition, protective additives, detergents, sunlight, especially ultraviolet rays, environmental pollution, climate changes, decrease the moisture and elasticity of the skin, causing the same to
appear dull, lifeless, dry and wrinkled over time. In order to achieve this balance, dermal applications with the help of cosmetic products have been known for years. To this end, moisturizers are the first choice in the treatment of dry skin and in ensuring the continuity of healthy skin.
Various mixtures have been developed to protect the barrier-forming property of the skin and to prevent wrinkles by maintaining the moisture balance. In CN102309749A, a combination of 8-15% collagen protein, 0.5-4% hyaluronic acid, 10-20% olive oil, 10-20% almond oil and others (various oils and petroleum jelly) is used for the purpose of developing a hand and foot cream. In WO2017133038A1, 8-10% lamb placenta extract, 45-60% pigskin collagen, 10-12% alginate, 5-8% olive oil-honey mixture are combined with water for developing an antiaging cream and moisturizer. In US8796217B2, olive oil is transesterified to accelerate the absorption of dermatological active substance through the skin. Caffeine, hyaluronic acid, collagen and antioxidants are used as dermatological active ingredients. In CN102198063B, the skin product is prepared by emulsifying the collage peptides, which are obtained by breaking up the fish skin, in olive oil. In CN101721343A, 1-10% deep sea skin collagen and 5-10% olive oil (or jojoba oil) are used as active ingredients for developing a face mask product. In CN104548190A, 10-25% collagen protein, 10-25% collagen tripeptide, 10-25% hyaluronic acid, 8-20% olive oil and other oils, plant extracts and vitamins are combined as a skin cream especially for breast enlargement.
In state of the art embodiments, one or more of the components required for moisturizing and repairing the skin are tried to be applied directly or in combination to the skin surface. In this application, taking into consideration the factors such as the rate of absorption by the skin and the duration of permanence on the skin surface, it is a known fact that the effectiveness of the product decreases shortly after the application and the skin regains its old, dry and lifeless appearance in a short time. Therefore, the desired effect cannot be achieved sufficiently. In order to prevent this outcome, products with high oil content such as petroleum jelly have been used to create a barrier on the skin, and it has been observed that said solutions are not sufficient in terms of user satisfaction and delaying skin aging, since they form a very thick, oily layer and do not have an additional function other than barrier formation. By means of the mixture of the present invention, the components needed by the skin are trapped in mesoporous silica particles (MSP) synthesized in-situ, thereby forming a barrier on the skin surface and ensuring controlled subcutaneous release. MSPs retain bioactive molecules such as olive oil, collagen and hyaluronic acid and ensure the release of said molecules over time. Thus, by means of this
effect, which is made permanent on the skin surface contrary to classical methods, suitable conditions are created for the skin to stay moist for a longer period of time and delay aging.
THE AIM OF THE INVENTION
By means of the mixture of the present invention, it is aimed to delay aging by repairing skin and preventing wrinkles and sagging, and heal various skin wounds in the field of dermocosmetics. For this purpose, it is aimed to develop a cream composition with olive oil for face, neck, hands, feet and body. The cream mixture of the present invention comprises the extraction of at least one polar active substance and at least one non-polar active substance from silane compounds and the entrapment, with the help of an emulsifier, of said substances in mesoporous silica particles (MSP), which are produced in-situ. Another aim of the present invention is the formation of a protective film layer on the skin by means of the MSPs and the long-term, controlled release on the skin by said layer without any external factors or stimuli. Another aim of the present invention is to eliminate skin dryness by preventing the skin from losing moisture thanks to the formed film acting as a barrier on the epidermis.
DETAILED EXPLANATION OF THE INVENTION
The human skin is an intelligent barrier composed of heterogeneous layers, which protects the body against various physical, chemical and microbiological factors, which prevents the loss of water and other fluids from the body, which is also permeable to substances applied for treatment, care and healing, and which acts as a barrier between the body and the outside world.
Anatomically, the skin is composed of three main layers. These layers are hypodermis, dermis and epidermis from bottom to top, and their thicknesses vary at different parts of the body. The dermis is the layer that makes the skin elastic and absorbs the substances applied to the skin. Collagen and elastin fibers are present in the dermis layer of the skin. Collagen and elastin are protein- structured fibers that make the skin elastic and tense. In case of any change in shape, collagen and elastin enable the skin to return to its original shape. The epidermis, which is the thinnest layer of the skin, is multi-layered, consisting of living and dead cells that renew themselves continuously throughout life, where the renewal process slows down with aging. The uppermost layer of the epidermis forms the upper surface of the skin and acts as a barrier. This layer consists of natural moisturizing factor and high concentrations of lipid ceramides.
Helping the skin retain moisture, ceramides are very important for a healthy skin. Ceramides form a barrier that prevents the skin from becoming dehydrated. The decrease in ceramides causes the water to evaporate rapidly and the skin to become dry. Studies show that the amount of ceramide decreases in dry skin and in the elderly and that the lipid composition of the uppermost layer of the epidermis deteriorates in dry skin that occurs in winter and especially a decrease in the ceramide amount is encountered.
Water is a vital substance for the skin, and the flexible and healthy appearance of the skin is directly proportional to its water holding capacity, and it is known that when there is not enough water in the environment, the skin dries out, loses its elasticity and cracks easily. Water provides softness and flexibility for the uppermost layer of the epidermis. Said water content in the uppermost layers of the epidermis is rapidly hydrated and dehydrated due to environmental factors. One of the most important functions of the epidermis is to act as a barrier to prevent the water in the living cells underneath from being lost by evaporation. Similar to the diffusion of water from the outside to the skin, there is also the diffusion of water from the lower layers of the skin to the upper layers. Water evaporates from a healthy skin at rates that vary from person to person. The diffusion rate of water from the living epidermis to the dead epidermis is not sufficient for dry skin to become elastic and soft again. Supplementing moisture from the outside is not very effective due to evaporation as long as the water is not retained in the uppermost layer of the epidermis.
While healthy skin is elastic and soft, dry skin is hard and rough. Water constitutes about a quarter of the last layer of the epidermis, which is the uppermost layer of the skin. The decrease in the water content in this layer causes dryness, cracking and itching in the skin. The decrease in the water content of this layer is continuous. In the simplest manner, the water lost by evaporation from the skin is supplied from the sub-epidermal and dermal layers. However, as a result of frequent bathing, damage due to sunlight or skin aging, water loss increases and the skin appears dry, rough and dandruffy. In dry skin, dead cells visibly shed from the top layer of the epidermis, causing a scaly appearance on the skin. Although the last layer of the epidermis is an important layer that prevents water loss from the skin, its protective feature decreases due to various external factors such as aging, wind, hot or cold weather, excessive skin cleaning with soap or contact with organic solvents.
During skin aging, which is caused by natural or environmental factors, the skin dries out by losing its moisture. Along with other effects, a skin, which is cosmetically old, assumes a dry, inelastic, lifeless appearance with visible wrinkles. From a cosmetic point of view, the reduction of epidermal lipids in the skin prevents the evaporation of water.
Skin aging is often dependent on age, sunlight, and other factors. The most significant age- related decrease occurs in the natural moisturizing factors of the skin, and this decrease increases age-related skin deterioration. In aging due to sunlight, the skin exposed to the sun prematurely ages due to UV rays. The surface of the skin has a wavy structure during the youth, and thanks to this structure, reflects sunrays and easily resists the external effects. However, due to sunrays and in time, the skin surface thickens, hardens and dries, and the ideal wavy structure of the skin is lost. The skin assumes a pale and tired appearance. The upper layers of the skin lose their integrity.
Other factors such as organic solvents, free radicals, cigarette smoke, detergents, soap, environmental factors, temperature increase or decrease cause the skin to dry by losing its moisture. Due to change in environmental conditions or diseases, the water content drops below 10%, and the skin surface again assumes a dry appearance with reduced elasticity. Moreover, in cold weather with low humidity, the top layer of the epidermis dries quickly. Due to the change of seasons and intercontinental travels, the skin tries to adapt itself to these changes. Drying may also occur when the skin cools down too much due to air conditioners.
It is believed that the epidermal barrier damaged due to water loss on the skin plays a leading role in various skin diseases. Appropriate use of moisturizers in skin diseases with such dry skin symptoms is of great importance in terms of treatment effectiveness. The regular and correct use of moisturizers may also decrease the amount of steroids that should be used.
In a healthy epidermis layer, the amount of hygroscopic substances, water and lipids, which play a key role in water retention and provide flexibility, should be balanced. Moisturizers are important in regulating the epidermal barrier and epidermal water content, and in giving the skin a smooth and healthy appearance. Moisturizers increase the water retention capacity of the skin thanks to their covering and water absorbing effects.
Olive oil obtained from olive fruit is one of the products with superior properties. All the beneficial minerals and vitamins found in olives are also present in olive oil. Natural olive oil can be used for cleaning body, hair and face, and as a cream for moisturizing similar areas.
Naturally, olive oil products provide moisture balance of the skin, and are known to support treatments against psoriasis, fungal diseases, skin chafing and other skin diseases. In addition to all these features of dermocosmetics obtained from olive oil, by adding hyaluronic acid and collagen suitable for the structure of the product, deep moisture, tension and elasticity, softness and freshness are provided in the skin, and effective results can be obtained in reducing wrinkles and ensuring facial rejuvenation. Hyaluronic acid, also known as hyaluronan, is a natural polysaccharide commonly found in the human body with the highest concentrations present in the eyes and joints. Hyaluronic acid is frequently used as one of various cosmetic product ingredients. When products containing hyaluronic acid (gels, creams, facial fillers, lotion, serum and implants, etc.) are examined comprehensively, it is concluded that they have remarkable anti-wrinkle properties. In the literature, it has been reported that hyaluronic acid has important contributions to the cosmetic and nutritional cosmetic efficacy for skin rejuvenation. Studies have shown that if hyaluronic acid has a low molecular weight, it becomes easier to pass through the skin.
Collagen is abundant in the skin. With aging, collagen loss occurs in the inner layers of the skin, the skin loses its elasticity and becomes vulnerable to damage. Wrinkles begin to form on the skin that loses its elasticity. The skin gradually assumes an aged appearance. By supplementing collagen, the elasticity of the skin increases and the moisture balance of the skin improves.
Collagen can be obtained from sources such as cattle or pigs, as well as from marine sources. Although there are various types of collagen, Type 1 collagen is the most abundant collagen type in the body and is found in the skin, organs and tendons. Collagen provides the elasticity of the skin and helps the healing of wounds, and products containing collagen are used to support medical treatment such as hair loss and nail breakage. The type and source of collagen, its molecular weight, and solubility are the main factors affecting the properties of collagen in usage areas. Collagen, which is preferred to be used in the mixture of the present invention, is collagen with a low molecular weight, especially obtained from marine sources in order to increase absorption.
It is supported by studies that hyaluronic acid and collagen combinations with appropriate type and molecular weight have a synergistic effect in increasing skin tension and elasticity, reducing wrinkles and rejuvenating the skin. Using hyaluronic acid and collagen with a suitable molecular weight for skin penetration in cosmetic products and homogeneous distribution and
stability thereof in the dermocosmetic product are very important in achieving the expected effective result. Moreover, it is stated that very effective results can be obtained with the controlled release of hyaluronic acid and collagen structures. To this end, mesoporous silica is highly preferred.
Mesoporous silica particles (MSP) are solid particles composed of porous structures with empty channels. Said empty channels enable MSPs to retain or encapsulate large quantities of bioactive molecules. The high surface area, pore volume, unique physicochemical properties and biochemical stability of MSPs, as well as other favorable properties such as easy surface modification, uniform and adjustable pore size, make them valuable inorganic drug carriers and theranostic agents for biological applications. In addition to the use of ready-made mesoporous silica, it is also possible to synthesize them in-situ as a result of hydrolysis condensation reactions from various silane compounds such as alkoxysilane. During the studies conducted, it is tried to impregnate mesoporous silica particles such as MCM-41 with polar active substances such as propolis or aloe vera for encapsulation.
Furthermore, during the studies wherein most drug molecules are encapsulated, an external factor (stimulus) or intervention is required for controlled release to occur. These stimuli can be heat, light, and ambient pH. Therefore, the release may not be continuous. Moreover, it is seen that in this type of encapsulation technique, more than one active substance, especially active substances with different polarities, is not encapsulated at the same time. In the present invention, instead of using MCM-41 as mesoporous silica, mesoporous silica particles are formed with the in-situ synthesis method by being homogeneously obtained in the reaction medium as a result of hydrolysis condensation of silicon alkoxides from the alkoxysilanes, that is, at the molecular level. The most important difference of this method is to create environments where both polar and non-polar active substances can coexist in mesoporous silica formed as a result of hydrolysis condensation of alkoxysilanes with the in-situ synthesis method by using emulsifiers during synthesis. In the prior art, silica particles are not synthesized by the in-situ synthesis method, but ready-made silica particles are used. Therefore, only an active substance with a uniform polarity can be encapsulated.
The present invention relates to a dermocosmetic preparation formed by entrapping polar and non-polar active substances in mesoporous silica particles synthesized in situ by hydrolysis condensation of the silane compound, comprising at least one polar active substance, at least
one non-polar active substance, at least one emulsifier, and at least one silane compound, with the aim of forming a film on human skin, which can release for a long time without external factors or intervention, to prevent water loss.
The polar active substance in the dermocosmetic preparation of the present invention can be one or more substances selected from the group consisting of collagen, hyaluronic acid, glutathione, and royal jelly, and is especially preferred to be collagen. For said hyaluronic acid, a hyaluronic acid with low molecular weight is preferred. For example, a hyaluronic acid with low molecular weight and collagen can also be preferred to be used together.
The non-polar active substance mentioned in the preparation of the present invention can be a substance selected from the group consisting of olive oil, shea butter, cocoabutter, and coconut oil, and is especially preferred to be olive oil. The emulsifier mentioned in the preparation of the present invention can be a substance selected from the group consisting of Polyoxyethylene sorbitan trioleate, Polyoxyethylene sorbitan monooleate, Polyoxyethylene sorbitan monostearate, Polyoxyethylene sorbitan monopalmitate, Polyoxyethylene sorbitan monolaurate, and is especially preferred to be polyoxyethylene sorbitan trioleate.
The silane compound mentioned in the preparation of the present invention can be a compound containing tetramethoxysilane, tetraethoxysilane, and is especially preferred to be tetramethoxy sil ane .
In case hyaluronic acid is not used as the polar active substance mentioned in the preparation of the present invention, at least one substance selected from the group consisting of collagen, glutathione and royal jelly can be used.
It is preferred that the collagen used in the preparation of the present invention is collagen derived from marine sources.
In the preparation of the present invention, propolis, biotin, vitamins C and E can also be used in double or triple combinations.
The dermacosmetic preparation of the present invention is especially in the form of cream and acts as a barrier by forming a film on the skin. By preventing water loss, it protects the skin against external effects and is characterized by a long-term controlled release especially from the skin to the subcutaneous tissue.
Claims
1. A dermocosmetic preparation formed by entrapping polar and non-polar active substances in mesoporous silica particles synthesized in situ by hydrolysis condensation of the silane compound, comprising at least one polar active substance, at least one non-polar active substance, at least one emulsifier, and at least one silane compound, with the aim of forming a film on human skin, which can release for a long time without external factors or intervention, to prevent water loss.
2. A preparation as in Claim 1, wherein said polar active substance is a substance selected from the group consisting of collagen, hyaluronic acid, glutathione, and royal jelly, and is especially collagen.
3. A preparation as in Claim 2, wherein said non-polar active substance is a substance selected from the group consisting of olive oil, shea butter, cocoa butter, and coconut oil, and is especially olive oil.
4. A preparation as in Claim 3, wherein said emulsifier is a substance selected from the group consisting of Polyoxyethylene sorbitan trioleate, Polyoxyethylene sorbitan monooleate, Polyoxyethylene sorbitan monostearate, Polyoxyethylene sorbitan monopalmitate, Polyoxyethylene sorbitan monolaurate, and is especially Polyoxyethylene sorbitan trioleate.
5. A preparation as in Claim 4, wherein said silane compound is a compound containing tetramethoxysilane, tetraethoxysilane, and is especially tetramethoxysilane.
6. A preparation as in Claim 5, wherein said polar active substance is not hyaluronic acid, comprising the hyaluronic acid in addition to the substances in Claim 2.
7. A preparation as in any one of the above claims, wherein the collagen from said polar active substances is collagen derived from marine sources.
8. A preparation as in any one of the above claims, wherein the hyaluronic acid from said polar active substances has a low molecular weight.
9. A preparation as in any one of the above claims, further comprising biotin and vitamins C and E as additives at the same time.
10. A preparation as in any one of the above claims, comprising propolis as protective agent.
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