WO2022186513A1 - Composition cosmétique pour les soins de la peau par régulation de la production de porphyrine et régulation de l'hyaluronidase dans le microbiome cutané - Google Patents

Composition cosmétique pour les soins de la peau par régulation de la production de porphyrine et régulation de l'hyaluronidase dans le microbiome cutané Download PDF

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Publication number
WO2022186513A1
WO2022186513A1 PCT/KR2022/002286 KR2022002286W WO2022186513A1 WO 2022186513 A1 WO2022186513 A1 WO 2022186513A1 KR 2022002286 W KR2022002286 W KR 2022002286W WO 2022186513 A1 WO2022186513 A1 WO 2022186513A1
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Prior art keywords
skin
cosmetic composition
acne
porphyrin
strain
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PCT/KR2022/002286
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English (en)
Korean (ko)
Inventor
형경은
안병준
강내규
Original Assignee
주식회사 엘지생활건강
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Priority to JP2023553374A priority Critical patent/JP2024508524A/ja
Priority to CN202280016884.2A priority patent/CN116940333A/zh
Publication of WO2022186513A1 publication Critical patent/WO2022186513A1/fr

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    • 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
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • 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
    • A61K8/60—Sugars; 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • 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
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • the present invention relates to a cosmetic composition that can beneficially control (rebalance) the growth and metabolites of skin flora.
  • the present invention also relates to a cosmetic composition capable of inhibiting the production of harmful substances on the skin, such as inhibiting the production of porphyrin in a porphyrin-producing strain, and inhibiting the hyaluronic acid degradation ability of a strain secreting a hyaluronic acid-degrading enzyme.
  • the skin contains millions of bacteria, fungi and viruses that make up the skin microbiome.
  • the microbiome refers to the total number of microorganisms present in a specific environment.
  • the genes of microorganisms that exist in the human body exist hundreds of times more than human genes, and they affect various functions in the human body.
  • microorganisms present in the skin also play an essential role in various metabolisms such as pathogen invasion, immune system regulation, and natural product decomposition, similar to the microorganisms in the intestine, and can affect human health.
  • the skin the largest organ of the human body, is colonized by beneficial microorganisms and acts as a physical barrier to prevent the entry of pathogens. When the barrier is weakened or the balance between symbionts and pathogens is disrupted, skin diseases or systemic diseases can develop. Studying the composition of the human skin site microbiota is useful for elucidating the pathogenesis of common skin diseases or association with skin conditions.
  • Cutibacterium acnes serves to inhibit the invasion or growth of pathogenic bacteria by decomposing sebum into glycerol and fatty acids to keep the skin slightly acidic. It is one of the major bacterial species that reside on the skin and plays an important role in maintaining the skin barrier. Therefore, it is undesirable to apply antibiotics with antibacterial or bactericidal action to the skin that can affect the entire C. acnes bacteria.
  • C. acne Cutibacterium acne
  • C. acne strain which is mainly possessed by healthy people rather than the acne patient group
  • C. acne strain which is mainly present in acne patients without being present in healthy skin
  • C. acne has different characteristics of secreting harmful molecules such as protease, lipase, hemolysin and porphyrin depending on the strain, and through these, harmful reactions of the skin such as decomposing host tissues or inducing inflammatory reactions can cause
  • porphyrin levels are observed to be higher in acne skin compared to healthy skin, and higher in acne lesions compared to non-lesion areas of acne patients.
  • the strain of C. acnes related to acne produces a higher concentration of porphyrin.
  • porphyrin can be produced in the case of S. aureus, which is a problem in atopic dermatitis or wound infection.
  • Porphyrin not only induces oxidative stress in the skin and promotes the expression of inflammatory cytokines in keratinocytes, but also induces a carbonylation reaction, a type of protein oxidation, which can darken the skin tone and make the skin look unhealthy. Therefore, it is used as a measurement index in various types of skin measuring devices and needs to be controlled as one of the major harmful factors of skin microorganisms.
  • the problem to be solved by the present invention is to inhibit the skin flora (for example, a specific C. acne strain) that has a relatively bad effect on the skin, such as causing acne, and has no significant effect on the skin (
  • it is to provide a cosmetic composition capable of rebalancing the skin flora by having relatively little influence on the growth of a specific C. acnes strain).
  • Another object to be solved by the present invention is to provide a skin improvement composition that controls oxidative stress and inflammation of the skin by inhibiting the production of porphyrin secreted by microorganisms present in the skin.
  • Another object of the present invention is to provide a skin improvement composition capable of preventing hyaluronic acid decomposition by inhibiting hyaluronic acid degrading enzyme secreted by microorganisms.
  • the present disclosure provides a skin microbiome comprising at least one selected from the group consisting of thiamine or a cosmetically acceptable salt thereof and saccharide isomerate as an active ingredient.
  • a cosmetic composition for conditioning is provided.
  • Another aspect of the present disclosure includes thiamine or a cosmetically acceptable salt thereof and any one or more selected from the group consisting of saccharide isomerate as an active ingredient, for controlling Cutibacterium acne in the skin microbiome A cosmetic composition is provided.
  • the cosmetic composition according to the present invention may be used for skin improvement through control of porphyrin production and/or control of hyaluronic acid degrading enzymes in skin flora.
  • a skin improvement composition that controls oxidative stress and inflammation of the skin by inhibiting the production of porphyrin secreted by microorganisms present in the skin to control harmful skin factors.
  • Another aspect of the present disclosure provides a skin improvement composition capable of preventing hyaluronic acid decomposition by inhibiting hyaluronic acid degrading enzyme secreted by microorganisms.
  • the cosmetic composition(s) according to the present disclosure includes thiamine or a cosmetically acceptable salt thereof as an active ingredient.
  • the present inventors tested various substances such as amino acids, amino acid derivatives, extracts, saccharides, vitamins, and fragrance ingredients, and completed the present invention by confirming that only the compounds of the present invention exhibit the desired effect in the present invention.
  • RT4 and RT5 based on the ribotype are known as acne-inducing types
  • RT6 is known to be abundant in healthy skin.
  • Ribotype RT4 e.g., HL053PA1 strain
  • RT6 e.g., HL110PA3 strain
  • cause acne has exist doesn't exist incubation rate Slow (6 days) Medium (4 days) porphyrin production High (500nM) Low (about 30 nM) HA resolution lowness very high
  • the HL053PA1 strain and the like produce excessive amounts of porphyrin, which can cause inflammation and oxidative stress, which can cause the secretion of inflammatory cytokines in the skin to cause inflammation such as acne. Inhibits the growth of the induced type (eg, RT4 or RT5, type IA based on recA type) and has relatively no effect on the growth of the acne-inducing type (eg, RT6), so the dominant species microbiome ecology can be maintained.
  • the induced type eg, RT4 or RT5, type IA based on recA type
  • the acne-inducing type eg, RT6
  • the cosmetic composition of the present disclosure inhibits the porphyrin production of the skin flora, particularly the porphyrin production of the acne-causing type C. acnes strain or the porphyrin production of the strain such as S. aureus, thereby inhibiting the occurrence of acne, or the skin dermis is dense. It is very helpful in increasing the skin tone, improving the symptoms of dry skin, or improving skin tone.
  • strains belonging to RT6 (or recA type standard type II) produce relatively few harmful factors such as porphyrin, but can produce an excess of hyaluronic acid degrading enzyme. It is also known that various bacteria such as S. aureus can produce hyaluronic acid degrading enzymes.
  • the cosmetic composition of the present disclosure is a cosmetic composition for improving skin elasticity through inhibition of hyaluronic acid decomposition of skin flora, in particular, inhibition of hyaluronic acid decomposition by non-acne type C. acne strain or S. aureus. may have beneficial effects.
  • This inhibition of hyaluronic acid decomposition also improves the density of the dermis, thereby showing good effects in moisturizing and preventing aging.
  • Cosmetically acceptable salts in the present invention include salts of the active compounds prepared with relatively non-toxic acids. Acid addition salts may be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, neat or with a suitable inert solvent.
  • cosmetically acceptable acid addition salts are acetic acid, propionic acid, isobutyric acid, oxalic acid, maleic, malonic, benzoic, succinic, suberic, fumaric ( fumaric), mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric acid, tartaric acid, methanesulfonic, and the like.
  • salts derived from non-toxic organic acids hydrogen chloride, hydrogen bromide, nitric acid, carbonic acid, monohydrogencarbonic, phosphoric, monohydrogenphosphate, dihydrogenphosphoric acid, sulfuric acid, monohydrogensulfuric acid, hydrogen iodide or phosphorous acid ( phosphorous acid) and its analogs.
  • salts of amino acids such as arginate and analogues thereof and analogues of organic acids such as glucuronic or galactunoric acids and analogues thereof.
  • Other examples of salts can be found in literature known in the art.
  • the total content of the active ingredients is preferably 0.00001 to 10% by weight based on the total weight of the cosmetic composition.
  • the active ingredient of the present invention may exist in unsolvated as well as solvated forms, including hydrates, ethanolates, and the like.
  • the active ingredient of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.
  • the cosmetic composition according to the present invention includes solutions, external ointments, creams, foams, nourishing lotions, softening lotions, packs, soft water, emulsions, makeup bases, essences, soaps, liquid detergents, bathing agents, sunscreen creams, sun oils, suspensions, Emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays may be prepared in a formulation selected from the group consisting of, but not limited to it is not
  • the cosmetic composition of the present invention may further include one or more cosmetically acceptable carriers to be formulated in general skin cosmetics, and conventional ingredients include, for example, oil, water, surfactant, humectant, lower alcohol, A thickener, a chelating agent, a colorant, a preservative, a fragrance, etc. may be appropriately mixed, but the present invention is not limited thereto.
  • the cosmetically acceptable carrier included in the cosmetic composition of the present invention varies depending on the formulation.
  • the formulation of the present invention is an ointment, paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures thereof may be used.
  • lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and in particular, in the case of a spray, additional chloro propellants such as fluorohydrocarbons, propane/butane or dimethyl ether.
  • a solvent, solubilizer, or emulsifier is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, propylene glycol, 1,3 -Butylglycol oil, in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol fatty esters, fatty acid esters of polyethylene glycol or sorbitan.
  • the formulation of the present invention is a suspension
  • a liquid diluent such as water, ethanol or propylene glycol
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters; Crystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanth may be used.
  • the formulation of the present invention is a soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolysates, isethionate, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars, etc. may be used as carrier components.
  • alkali metal salts of fatty acids fatty acid hemiester salts, fatty acid protein hydrolysates, isethionate, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars, etc.
  • composition for cosmetics, food, or personal care according to the present invention contains the ingredients according to the present invention within the content limit allowed by the relevant laws and regulations of each country.
  • the composition provided in the present disclosure has an effect of inhibiting the growth of major flora of the skin, for example, the growth of C. acne type frequently present in acne patients among C. acnes and the production of harmful factors (porphyrin). indicates.
  • it can exhibit the effect of inhibiting the activity of hyaluronidase produced by this strain without affecting the growth of C. acne type, which is mainly present in non-inflammatory skin.
  • it may exhibit an effect of inhibiting porphyrin production and/or hyaluronidase activity generated by bacteria present in the skin, such as S. aureus, in addition to the C. ance strain.
  • Figure 2 is a result of evaluating the effect of the thiamine salt on a non-pathogenic strain of Cutibacterium acnes.
  • Figure 3 is a result of evaluating the effect of the thiamine salt on the production of porphyrin of the pathogenic and non-pathogenic strains of Cutibacterium acnes.
  • a is a result of evaluating the effect on the strain growth of HL053PA1, a C. acnes strain associated with acne
  • b is a result of evaluating the effect on the growth of a strain of HL110PA3, a healthy skin-related C. acnes strain
  • c is the result of evaluating the effect on porphyrin production of HL053PA1, a C. acnes strain associated with acne skin
  • d is the result of evaluating the effect on the degradation rate of hyaluronic acid of HL110PA3, a healthy skin-related C. acne strain.
  • the HL053PA1 strain which is a Cutibacterium acne type, which is mainly present in acne patients, was cultured and activated in BHI broth, and then re-inoculated at the same turbidity. At this time, thiamine HCl was treated at a concentration of 1 w/v% and absorbance was measured at 595 nm after incubation for 7 days to confirm the effect on strain growth. The results are shown in FIG. 1 .
  • the HL110PA3 strain which is a C. ance type mainly present only in normal skin, was cultured and activated in BHI liquid medium, and then re-inoculated at the same turbidity. At this time, thiamine HCl was treated at a concentration of 1%, and absorbance was measured at 595 nm after 7 days of incubation to confirm the effect on strain growth. The results are shown in FIG. 2 .
  • C. acnes HL053PA1 and HL110PA3 strains were respectively cultured and activated in BHI broth, and then re-inoculated at the same turbidity.
  • thiamine HCl was treated at a concentration of 1%, and the strain culture was recovered after 7 days of incubation.
  • 400 ⁇ l of the bacterial culture was extracted by adding ethyl acetate and acetic acid (4: 1, vol/vol). The extract was centrifuged to recover the upper layer containing porphyrin through layer separation.
  • the recovered supernatant was dissolved in 1.5 M HCl, and the layers were separated by centrifugation to recover the lower layer.
  • the recovered soluble phase was measured for fluorescence at 405 nm/620 nm. The results are shown in FIG. 3 .
  • the acne-associated C. acnes strain produced a greater amount of porphyrin than the C. acnes strain present in normal skin.
  • Thiamine HCl treatment significantly reduced the amount of porphyrin present in the culture of acne-associated strain HL053PA1.
  • S. aureus strains were re-inoculated at 1/100 concentration activated by culturing in BHI broth.
  • the strain culture was recovered after treatment with thiamine HCl at a concentration of 1 w/v% and culturing for 24 hours.
  • 400 ⁇ l of the bacterial culture was extracted by adding ethyl acetate and acetic acid (4: 1, vol/vol). The extract was centrifuged to recover the upper layer containing porphyrin through layer separation.
  • the recovered supernatant was dissolved in 1.5 M HCl, and the layers were separated by centrifugation to recover the lower layer.
  • the recovered soluble phase was measured for fluorescence at 405 nm/620 nm. The results are shown in FIG. 4 .
  • the HL110PA3 strain was activated by culturing in BHI broth and then re-inoculated to the same turbidity. At this time, thiamine HCl was treated at a concentration of 1%, and the culture medium was recovered after 7 days of incubation.
  • the hyaluronic acid and the culture medium were mixed and reacted at 37° C. for 20 minutes. After the reaction was completed, 1% BSA sodium acetate buffer was added to aggregate the remaining hyaluronic acid and BSA, and the degree of decomposition of hyaluronic acid was confirmed by taking absorbance at 540 nm. The results are shown in FIG. 5 .
  • HL110PA3 a non-pathogenic strain of C. acnes, is generally classified as a healthy skin type C. acne because it is isolated from healthy skin without inflammatory lesions. can do. While about 85% of hyaluronic acid was decomposed for 20 minutes when treated with untreated culture medium, about 60% of hyaluronic acid was decomposed in the culture medium of the experimental group treated with Thiamine HCl, indicating that it can inhibit the degradation of hyaluronic acid by 30% compared to the control group. Confirmed.
  • S. aureus strains were re-inoculated at 1/100 concentration activated by culturing in BHI broth. After treatment with thiamine HCl at a concentration of 1% and cultured for 24 hours, the culture medium was recovered. To measure the activity of the hyaluronic acid degrading enzyme secreted by S. aureus, the hyaluronic acid and the culture medium were mixed and reacted at 37° C. for 90 minutes. In order to measure the hyaluronic acid remaining without degradation, the remaining hyaluronic acid was quantified using a hyaluronan ELISA kit.

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Abstract

La présente divulgation concerne une composition cosmétique qui est conçue pour inhiber la croissance d'un microbiome cutané nocif pour la santé dermatologique et pour réduire la production de la porphyrine à facteur nuisible, et ce, sans aucune influence sur les microbiomes cutanés non nocifs pour la santé dermatologique, ce qui permet de sainement rééquilibrer le microbiome cutané. La présente divulgation concerne également une composition cosmétique permettant d'éliminer la production de porphyrine dans des souches qui produisent de la porphyrine. La présente divulgation concerne une composition de soin de la peau qui permet d'hydrater la peau et de prévenir le vieillissement de la peau par inhibition de l'activité de l'hyaluronidase sécrétée par un microbiome cutané pour éliminer la dégradation de l'acide hyaluronique.
PCT/KR2022/002286 2021-03-03 2022-02-16 Composition cosmétique pour les soins de la peau par régulation de la production de porphyrine et régulation de l'hyaluronidase dans le microbiome cutané WO2022186513A1 (fr)

Priority Applications (2)

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JP2023553374A JP2024508524A (ja) 2021-03-03 2022-02-16 皮膚常在菌のポルフィリン生成の調節およびヒアルロン酸分解酵素の調節を通じた皮膚改善用化粧料組成物
CN202280016884.2A CN116940333A (zh) 2021-03-03 2022-02-16 通过调节皮肤常居菌的卟啉产生和调节透明质酸分解酶来改善皮肤的化妆料组合物

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KR10-2021-0028329 2021-03-03
KR1020210028329A KR102548896B1 (ko) 2021-03-03 2021-03-03 피부 상재균의 포피린 생성 조절 및 히알루론산 분해 효소 조절을 통한 피부 개선 화장료 조성물

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WO2005009400A1 (fr) * 2003-07-23 2005-02-03 N.V. Perricone, M.D., Limited Traitements topiques a la benfotiamine
KR20090003144A (ko) * 2006-07-26 2009-01-09 주식회사 코씨드바이오팜 알리티아민을 함유하는 화장료 조성물
KR20180024026A (ko) * 2015-07-23 2018-03-07 마리 케이 인코포레이티드 국소 피부 제형들
WO2020052916A1 (fr) * 2018-09-11 2020-03-19 Unilever N.V. Composition topique comprenant un isomérat de saccharide pour un équilibrage du microbiome
KR20200094178A (ko) * 2017-11-29 2020-08-06 액세스 비지니스 그룹 인터내셔날 엘엘씨 피부 마이크로바이옴의 변형을 위한 방법 및 국소 조성물
CN111773161A (zh) * 2020-06-16 2020-10-16 广州优理氏生物科技有限公司 一种益生元组合物及其制备方法和应用
US20210000728A1 (en) * 2019-07-03 2021-01-07 Jamrm, Llc Formulations for Enhancing Skin Firmness, Density and Thickness

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WO2005009400A1 (fr) * 2003-07-23 2005-02-03 N.V. Perricone, M.D., Limited Traitements topiques a la benfotiamine
KR20090003144A (ko) * 2006-07-26 2009-01-09 주식회사 코씨드바이오팜 알리티아민을 함유하는 화장료 조성물
KR20180024026A (ko) * 2015-07-23 2018-03-07 마리 케이 인코포레이티드 국소 피부 제형들
KR20200094178A (ko) * 2017-11-29 2020-08-06 액세스 비지니스 그룹 인터내셔날 엘엘씨 피부 마이크로바이옴의 변형을 위한 방법 및 국소 조성물
WO2020052916A1 (fr) * 2018-09-11 2020-03-19 Unilever N.V. Composition topique comprenant un isomérat de saccharide pour un équilibrage du microbiome
US20210000728A1 (en) * 2019-07-03 2021-01-07 Jamrm, Llc Formulations for Enhancing Skin Firmness, Density and Thickness
CN111773161A (zh) * 2020-06-16 2020-10-16 广州优理氏生物科技有限公司 一种益生元组合物及其制备方法和应用

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Title
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KR102548896B1 (ko) 2023-06-27
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JP2024508524A (ja) 2024-02-27

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