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WO2016190661A1 - Composition cosmétique pour inhiber le prurit et soulager la dermatite atopique, contenant de l'isosécotanapartholide en tant que substance active - Google Patents

Composition cosmétique pour inhiber le prurit et soulager la dermatite atopique, contenant de l'isosécotanapartholide en tant que substance active Download PDF

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Publication number
WO2016190661A1
WO2016190661A1 PCT/KR2016/005534 KR2016005534W WO2016190661A1 WO 2016190661 A1 WO2016190661 A1 WO 2016190661A1 KR 2016005534 W KR2016005534 W KR 2016005534W WO 2016190661 A1 WO2016190661 A1 WO 2016190661A1
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Prior art keywords
cosmetic composition
atopic dermatitis
itching
inhibiting
skin
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Ceased
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PCT/KR2016/005534
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English (en)
Korean (ko)
Inventor
한창성
김진국
이강혁
김건용
박소연
장준환
윤지원
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Hyundai Bioland Co Ltd
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SK Bioland Co Ltd
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Priority to CN201680030345.9A priority Critical patent/CN107920974A/zh
Publication of WO2016190661A1 publication Critical patent/WO2016190661A1/fr
Anticipated expiration legal-status Critical
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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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • 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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • 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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • 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

Definitions

  • Cosmetic composition for suppressing itching and improving atopic dermatitis containing isosecotanapasolide as an active ingredient
  • the present invention relates to a cosmetic composition for inhibiting itching and improving atopic dermatitis, and more particularly, to a composition for improving itching and improving atopic dermatitis, containing isosecotanapartholide (Isosecotanaparthol ide) as an active ingredient.
  • isosecotanapartholide isosecotanapartholide
  • Itching is a sensation caused by many skin diseases and is mainly associated with diseases such as atopic dermatitis, contact dermatitis, urticaria, nodular fever, um, chronic simple thyroid, insect bites, and eczema.
  • This itch is caused by irritation of the skin nerve. When severely scratched or rubbed to remove the itch, hepatitis, cracks, ulcers, swelling, pigmentation, etc., and the skin becomes thicker if persisted. (Greaves et al, The Lancet., 348, pp. 938-40, 1996)
  • Cytokines play an important role in the intercellular interaction mechanisms, among which interleukin-3UIL-31 belongs to the interleukin-6 family, which is interleukin-31A and 0SMR (0ncostain M receptor). It consists of a heterologous Heterodimeric receptor complex. Interleukin-31 plays an important role in innate imunity and adaptive immunity in skin tissue in close proximity to the environment. Increased expression of interleukin-31 is associated with allergy or inflammatory bowel disease, as well as diseases including itching, such as atopic dermatitis. (C. Cornel issen et al.
  • Interleukin-33GL-33) is present in cells of the skin surface. Severe scratches, pollen, ticks, etc. are stimulated to come out of the cell and combine with white blood cells, causing allergies. In patients with atopic dermatitis, interleukin-33 is known to be abundant.
  • mice that manipulated genes to make interleukin-33 about 10 times greater than wild-type, itching accompanied by itching on the face, legs, and tail of rats, leading to thickening of the skin. Symptoms of atopic dermatitis were shown. GM mice had about three times more mast cells that secrete histamine, which is the basis for itching. (Imai et al. PNAS, 2013, vol. 110, no. 34, 13921-13926)
  • interleukin-31 and interleukin-33 are associated with skin inflammation and itching caused by dermatitis. Therefore, by investigating the effect of reducing the expression of interleukin-31 and interleukin-33 in human kerat inocytes, it is possible to search for foods, pharmaceuticals and cosmetic ingredients that are effective in relieving itching and treating dermatitis. It may be used to develop an itch treatment.
  • atopic dermatitis is a chronic and recurring inflammatory skin disease that can be easily diagnosed through the skin's swelling, eczema, itching, and inflammatory reactions. Is not yet clear. In the last two to three decades, atopic dermatitis has increased significantly compared to rural and developing countries, especially in westernized countries, supported by hygiene hypothesis (hygiene hypothesis). This hypothesis suggests that the growth of the immune system requires stimulation from the external environment, including bacteria, or other problems such as allergies due to problems with the immune system. Yazdanbakhsh, M., PG Kremsner, and R. van Ree, Allergy, Parasites, and the hypothesis Science, 296 (5567): 490-494, 2002].
  • Atopy is a complex immune response that affects certain sensitive genes, the environment, the extent of damage to the skin's outer walls, and immune factors.
  • the main symptoms of atopy include swelling and eczema in the face of young children and eczema in the flexion of the joints in adults. Above all, the symptoms of itching are severe and cause serious problems in the social activities of patients. Dermatitis adds serious mental distress to a patient, as well as physical suffering from the disease.
  • TSLP thymic stromal lymphopoietin
  • TSLP also known as the 'master switch' of allergic inflammation, affects important cells that cause skin inflammation such as mast cells, basophils, and eosinophils, affects both innate and acquired immune responses, and induces Th2 immune reactions to induce atopic dermatitis.
  • Ziegler SF, Art is D. Sensing the out si de world: TSLP regulates barrier immunity. Nat Immunol 2010; 11: 289 ⁇ 293.
  • TSLP is increased in the skin and blood of atopic dermatitis patients.
  • allergens increase PAR-2 expression of keratinocytes, TSLP secretion in the epidermis increases, which causes Th2 inflammatory reactions to prevail, leading to clinical manifestations of atopic dermatitis.
  • TSLP has been discussed as an important mediator for the progression of atopic dermatitis to asthma and allergic rhinitis in allergic march.
  • TSLP is considered to be a target to prevent the development of atopic dermatitis and to prevent the progression to allergic march [ Zhang Z, Hener P, Frossard N, Kato S, Metzger D, Li M, Chambon P. Thymic stromal lymphopoiet in overproduced by kerat inocytes in mouse skin aggravates experimental asthma. Proc Nat 1 Acad Sci USA * 2009; 106: 1536-1541.
  • atopy dryness caused by dysfunction and transepi dermal water loss (TEWL) of the skin barrier, mainly accompanied by swelling and inflammatory reactions. Therefore, regular skin softening lotion and the use of moisturizers are generally used in the treatment of atopy.
  • glucocorticosteroids are known to be most effective in the treatment of early symptoms of atopic dermatitis. This method not only has anti-inflammatory effects, but also prevents colonization of S. aures (Staphylococcus aures) to prevent secondary infection. It also prevents atopic symptoms from getting worse. Topical steroids should be used for a short period of time to treat early eczema symptoms, and when used in combination with skin softening lotions, the effect is much better.
  • Pimecrolimus and tacrolimus are calcineurin inhibitors with immunomodulatory effects and are widely used as anti-inflammatory drugs. It is effectively used for sensitive areas such as the face because it lacks steroids, but the disadvantage is that you may feel temporary stinging.
  • topical antimicrobial ointment prevents the growth of the bacteria and alleviates atopic symptoms.
  • This method is more effective because it can prevent secondary infection when used with steroid products, but it is recommended to use an appropriate amount for a short period of time because it is resistant to long term use.
  • cyclosporin ACcyclosporin A which blocks calcineurin dependent pathways, is used for oral administration by reducing the expression of proinflammatory cytokine such as IL-2 and IFN-gamma. This method is only suitable for patients with severe incurable diseases because it can be toxic to the kidneys despite its effective ability to cure atopy.
  • atopic dermatitis treatments have been used to suppress calcineurin and reduce the cytokine expression, such as cyclosporin and FK506.
  • the steroid-based external treatments that reduce resistance and relieve skin itching and pruritus also have problems such as reduced immunity and growth inhibition when children are used for a long time.
  • Azathioprine is a representative immunosuppressor effective for skin diseases by affecting purine nucleotide synthesis and metabolism.
  • corticosteroids There is a very effective phototherapy when used. This is a method that exposes UVB wavelength of 280-320 ⁇ and UVA wavelength of 340-400nm to the whole body, and it is reported that it is very effective for adults, but young children can use it only after puberty because the skin is still weak.
  • the present inventors have endeavored to develop an excellent substance capable of improving atopic skin without side effects and skin irritation.
  • natural product-derived compound isosecotanapartholide isosecotanapartholide
  • TSLP thymi c stromal lymphopoiet in the highest protein of abnormal signaling caused by immune imbalance which is the root cause of atopic dermatitis, was excellent in cytokine inhibition and MDC in HaCaT cells.
  • the atopic skin can be improved overall by inhibiting the expression of chamokine of TARC and completed the present invention.
  • the main object of the present invention is to suppress the itching and relieve itching by inhibiting IL-3K Inter leukin-31) or IL-33 (Inter leukin-33) among the cytokines that cause various itching It is to provide a cosmetic composition for suppressing and alleviating itching containing napa solide as an active ingredient.
  • another object of the present invention is a cytotoxic, non-cytotoxic top-level protein of abnormal signaling caused by immune imbalance that is a fundamental cause of atopic dermatitis
  • the present invention provides a cosmetic composition for improving atopic dermatitis, which is excellent in TSLP cytokine inhibitory activity and excellent in inhibiting the expression of MDA and TARC by chamoine expression as an active ingredient.
  • the present invention provides a cosmetic composition for inhibiting and alleviating itching, containing isosecotanaparthol ide represented by the following formula [1] as an active ingredient.
  • the present invention provides a cosmetic composition for improving atopic dermatitis, containing isosecotanapartholide (Isosecotanaparthol ide) represented by the following formula [1] as an active ingredient.
  • isosecotanapartholide Isosecotanaparthol ide
  • the compound "isocecotanapasolide” identified in the present invention is various It is contained in natural products. For example, it is contained in the heather (Artemisi a iwayomogi), the leaflets (Artemi sia princeps var. Oriental is 'Pampan' Hara), or the side.
  • the isosecotanapasolide compound has been disclosed as a novel whitening agent, whitening cosmetic composition [JP 5307369]. However, there is no study on the inhibition and alleviation of the itch or improvement of atopic dermatitis of the compound "isoceconata pasolide” identified in the present invention.
  • isosecotanapasolide identified from the leaf lobe is not only effective in suppressing and alleviating itching, but also in improving atopic dermatitis, thereby completing the present invention.
  • the term 'itch itch' in the present invention is also referred to as pruritus, which means that it is caused by various dermatitis.
  • the isosecotanapaholide (Isosecotanaparthol ide) may be contained from 0.00001 to 5% by weight relative to the total weight of the cosmetic composition, preferably 0.0001 to 0.5% by weight is contained, characterized in that not limited to Do not. If isosecotanapasolide is contained in less than 0.0001% by weight, the effect of itching and atopic dermatitis due to the active ingredient is too small when added to cosmetics, and when it exceeds 0.5% by weight, there is no problem in skin safety or effect. Since the isosecotanapa solide is purified from natural products, it is difficult to obtain in large quantities, which is undesirable from an economic point of view.
  • the isosecotanapartholide may be prepared by a chemical synthesis method known in the art or may be separated from natural products, preferably from a leaf (Artemi sia princeps var. Or iental is) It is characterized by being separated.
  • the leaflets were extracted at room temperature or 60 ° C using a concentration of 0 to 953 ⁇ 4 ethanol and extracted for 3 days or more, and then the filtrate obtained by filtration was concentrated to remove the solvent to obtain an extract.
  • Nucleic acid after dispersing about 2 to 20 times its weight, preferably about 2 to 5 times the volume of water.
  • the non-polar solvent soluble extract of the leaflets obtained by the above-mentioned method was dissolved in an alcohol having 1 to 4 carbon atoms, preferably in methanol and adsorbed onto a C18 column, followed by a nonpolar solvent, preferably dichloromethane: methane.
  • the mixture was mixed to obtain the fractions, adsorbed onto silica gel, followed by silica gel column chromatography 2 to 5 times to separate the active fractions, and finally, the isosecotanapasolide of the present invention was obtained using high performance liquid chromatography. can do.
  • the present inventors paid attention to isosecotanapasolide, which is a component that inhibits the expression of interleukin-31 and interleukin-33 in skin cells, after thin-film chromatography of the leaf extracts and separation of each component.
  • the isosecotanapasolide is a single compound that is purified from wormwood or asteraceae, and there is no example used to relieve itching, and for the first time in the present invention, the isosecotanapasolide as a composition for suppressing itching in itching It is found that it can be used.
  • the cause or form causing the itch is not particularly limited, but preferably, inflammatory dermatitis, atopic dermatitis, dermatitis due to roughness of skin, sweat band, erosion, frostbite, contact dermatitis, seborrheic dermatitis, psoriasis Or is caused by the psoriasis.
  • the continuous itch causes the skin to be constantly rubbed, scratched or pinched.
  • secondary skin damage such as skin rash, abrasion, thymus, positivity, hyperpigmentation or reduction of pigmentation is induced, and various substances inducing inflammatory reaction in the skin are secreted, and this secretion is itchy again. This increases the circulation of itching-scratching.
  • the isosecotanapa solide (I sosecotanapar t ho ⁇ de) is IL-31 (Int er 1 euki n-31) or It is characterized by exhibiting an itching suppression and alleviation effect by reducing the release amount of cytokines such as IL-33 (Inter leukin-33).
  • the isosecotanapasolide of the present invention is excellent in inhibiting the expression of IL-31 and IL-33 associated with itching in human keratinocytes (HaCaT cel l). Confirmed. From these results, it can be seen that isosecotanapasolide of the present invention can suppress and relieve itching by inhibiting the expression of the cytokines IL-31 and IL-33 released when itching occurs. (See Experimental Examples 2 to 4).
  • the isosecotanapasolide of the present invention inhibits the expression of IL-1beta (IL- ⁇ ) and interleukin-6 (IL-6) induced by TNF-alpha and IFN-gamma and is associated with immune hypersensitivity reactions. It was confirmed that the inhibition of the expression of interleukin-6 and interleukin-1beta can be significantly reduced, and it was confirmed that isosecotanapasolide exhibited a very good anti-itch effect (see Experimental Example 2).
  • the isosecotanapaholide (Isosecotanaparthol ide) is characterized in that it has an atopic dermatitis improvement effect by thymi c stromal lymphopoi et in (TSLP) inhibitory ability.
  • TSLP thymi c stromal lymphopoi et in
  • the isosecota 8 nafa solide (Isosecota ⁇ arthol ide) is characterized in that it has an atopic dermatitis improvement effect by inhibiting the expression of macrophage-derived chemokine (MDC).
  • MDC macrophage-derived chemokine
  • the isosecotanapartholide (Isosecotanaparthol ide) is characterized in that it has an atopic dermatitis improvement effect by inhibiting the expression of thymus and act ivat ionregulated chemokine (TARC).
  • the cosmetic composition is supple cosmetics, nourishing cosmetics, essence, nutrition lotion, nutrition cream, eye cream, massage cream, cleansing cream, cleansing products, cleansing water, powder, pack, hair cosmetics, body lotion, body At least one formulation selected from the group consisting of creams, body oils, body essences or body cleansers.
  • the hair cosmetics include hair tonic, hair conditioner, hair lotion, shampoo, hair rinse, treatment, hair cream, hair oil, hair dryer, hair preservative, hair colorant, hair wave agent, hair bleach, hair gel, hair Glazes, hairdressers, hair lacquers, hair moisturizers, hair mousses and hairsprays, but is not limited thereto.
  • the present invention when used as a cosmetic composition, in addition to isosecotanapasolide as an active ingredient, it may include components commonly used in cosmetic compositions, such as water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingos. Lipid and seaweed extracts and the like.
  • a compounding component which may be added to a cosmetic composition it is an oil-fat component and a moisturizer .
  • Emollients Emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, blood stimulants, antiseptics, restrictions First, purified water and the like can be mentioned.
  • composition of the present invention when used as a pharmaceutical composition, isosecotanapasolide as an active ingredient may be used depending on the use, formulation, and formulation purpose, so long as it can exhibit an itch inhibiting effect or an atopic dermatitis improving activity. It can be included in an amount (effective amount).
  • the pharmaceutical composition of the present invention may contain isosecotanapasoleide in an amount of 0.0001 to 0.5% by weight based on the total weight of the composition.
  • composition of the present invention when used as a pharmaceutical composition, it may further include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
  • the preferred dosage of the pharmaceutical composition depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. have.
  • the pharmaceutical composition of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
  • composition of the present invention when used as a pharmaceutical composition, it can be administered orally or parenterally, and is preferably applied by parenteral administration, more preferably by topical application (topi cal appl i cat ion).
  • the pharmaceutical composition of the present invention can be prepared in any formulation that can be applied to the skin, such as liquid, cream, paste, solid, etc., cream, lotion, liquid essence type to improve itching or atopic dermatitis by adding conventional additives And aerosol types of these formulations.
  • the isosecotanapasolide of the present invention can be safely used in cosmetic compositions because it has no cytotoxicity and skin side effects, and at the same time inhibits the expression of interleukin-31 and interleukin-33 receptor in keratinocytes and at the same time TNF- It inhibits the expression of interleukin-1 beta and interleukin-6 caused by alpha and IFN-gamma, thereby showing an excellent effect on suppressing and alleviating itching.
  • isosecotanapasolide of the present invention is TSLP thymi c stromal lymphopoiet in the top protein of abnormal signaling caused by immune imbalance which is a fundamental cause of atopic dermatitis
  • the cytokine inhibitory ability is excellent and the ability to inhibit the expression of chamokine expression of MDC and TARC in HaCaT cells, it is possible to improve atopic skin.
  • Figure 1 shows the analysis of high performance liquid chromatography of the leaf extract.
  • Figure 2 shows the analysis of high performance liquid chromatography of isosecotanapasolide 0.05% solution.
  • FIG. 3 is a diagram showing the results of confirming the cytotoxicity of isosecotanapasolide.
  • Figure 4 is a view showing the results confirming the IL-lbeta secretion control of isosecotanapa solide.
  • 5 is a view showing the results of confirming the regulation of IL-6 secretion of isosecotanapasolide.
  • FIG. 6 is a diagram showing the results of confirming the regulation of IL-33 secretion of isosecotanapasolide.
  • FIG. 7 is a diagram showing the results of confirming the regulation of IL-31 secretion of isosecotanapasolide.
  • FIG. 8 is a diagram showing the results of confirming the IL-31 and IL-33 inhibitory effects of isosecotanapasolide at the gene level.
  • FIG. 9 is a diagram showing the results of confirming the IL-31 and IL-33 inhibitory effects of isosecotanapasolide at the protein level.
  • 10 is a view showing the results of evaluating the itching effect of isose.Cotanapasolide through clinical trials.
  • Fig. 11 shows the results for TSLP inhibitory activity of isosecotanapasolide.
  • FIG. 13 shows the results for the MDC-1 inhibitory ability of isosecotanapasolide Drawing.
  • the compound isosecotanapasolide was isolated from Artemisia princeps as follows.
  • methanol 80: 1.
  • silica gel column chromatography was carried out under the conditions of dichloromethane: methanol (80: 1 ⁇ 50: 1 ⁇ 30: 1 ⁇ 20: 1 ⁇ 15: 1 ⁇ 5: 1 ⁇ 1: 1) to increase the eluate.
  • the NMR instrument analyzed the structure of the compound separated by Varian (Garian, GEMINI, 400 MHz) and C 13 -NMR, and VMS (Aldrich) solvent. It was confirmed that the NMR results are consistent with the published data. [Hanna Ahn. et al. , Arch Pharm Res Vol 26, No 4, 301-305, 2003]
  • Example 2 Preparation of Purified Isosecotanapasolide 0.05% Solution
  • CCK-8 assay was performed using a constituent cell line of human skin, a stratum corneocyte HaCaT cell line (CLC Celll ine serve ice, Germany). It was. The cell viability was measured by CCK-8 ki t. Cel l on a 96 wel l plate 2.5 ⁇ 10 4 ⁇ 90 / ⁇ per wel l After dispensing into media, the cells were incubated for 24 hours in a 37 0 C C0 2 incubator.
  • isocetacoanapasolide (1.25, 2.5, 5, 10 ng / mL) was applied to HaCaT cells by concentration, and applied for 24 hours, followed by kit sol'n lO, shaded, and placed in a 37 ° C incubator 1 After time the absorbance was measured at 450 ran. The results are shown in FIG. As shown in Figure 3, it was confirmed that no cytotoxicity at all concentrations treated with isosecotanapasolide of the present invention.
  • Experimental Example 2 Confirmation of cytokine secretion regulation (ELISA)
  • ELISA analysis was performed to confirm the regulation of cytokine secretion against isosecotanapasolide isolated in Example 1.
  • HaCaT keratinocytes used in the experiment were dispensed with 2xl0 5 cells / mi in a 60 ⁇ dish and attached at 37 ° C, 5% C0 2 incubator for 24 hours.
  • IFN_Y 10 ng / mL
  • TNF-cx 10 ng / mL
  • cytokines of IL-lbeta, IL-6, IL-31, and IL-33 were measured using an ELISA kit sold by eBioscience (CA, USA). In more detail, 100 / ⁇ of capture Ab diluted with coating buffer was added per well and overnight at 4 0 C. lx assay diluent per well
  • This reaction was performed using arbitrary primers and M-MLV reverse transcriptase (Invitrogen Corp., CA, USA).
  • the general PCR conditions 30 35 cycles at 94 ° C for 2 10 min, 94 ° C for 30 s 3 min, 50 ° C-58 ° C for 30 s 1 min, 72 ° C for 30 s 1 min, and 72 It was carried out at ° C for 4 7 min conditions.
  • Image is
  • Example 2 To determine the degree of inhibition of cytokine release at the protein level using isosecotanapasolide isolated in Example 1 as a sample. Western blot analysis was performed. More specifically, hDPCs are dissolved in RIPA buffer containing 50 mM Tris, pH 8.0, 150 mM NaCl, .1% NP-40, 0.1% SDS, 0.5% deoxycholic acid, ImM PMSF Mix protease inhibitor (Roche Applied Science, Indianapolis, IN) for 15 minutes on ice at 4 ° C
  • the cDNA to be used for real-time PCR was synthesized by extracting total RNA after 24 hours of treatment of the compound isosecotanapasolide lysate of Example 2 with HaCaT cell line. Specifically, TrizoKlnvitrogen, Carlsbad, Total RNA was extracted using li). In order to perform cDNA synthesis using Total RNA, the total reaction solution 20 // «was composed of the following compositions.
  • reaction After reacting at 37 0 C for 15 minutes, reaction was performed at 85 ° C for 5 seconds and treated with 4 ° C. The finished cDNA was used for real-time PCR analysis in the following manner.
  • TSLP thymic stromal lymphopoiet in
  • TSLP thymic stromal lymphopoiet in
  • type 2 helper T cell mediated immune deflection which is thought to be the cause of atopic dermatitis.
  • quercetin (sigma), naringin (sigma), and hesperidin (sigma), which are well-known compounds for anti-inflammatory effect, were dissolved in DMS0 at the same concentration, and then TSLP cytokines were changed.
  • Final reaction samples were prepared and measured using an Applied Biosystems ABI 7500 Real-time PCR system (AB Applied Biosystems, USA).
  • a semi-aqueous solution for the analysis of GAPDH and TSLPCthymic stromal lymphopoietin was performed to perform real-time PCR.
  • the reaction liquid for GAPDH analysis was GAPDH (Hs99999905, Lot 682967) 1 ⁇ and. DW 5 ⁇ and Master Mix (2X) (TaqMan Gene Expression Master Mix L / N 0810037, P / N 4369016) and cDNA were made by mixing well.
  • the reaction solution for the analysis of TSLPCthymic stromal lymphopoietin was made by well mixing TSLP (Hs00263639) 1 ⁇ and DW 5 / ⁇ and Master Mix (2X) (TaqMan Gene Expression Master Mix L / N 0810037, P / N 4369016) with cDNA. .
  • the prepared reaction solution was placed in a real-time PCR reaction plate (optical 96-well Reaction Plate with Barcode, part No.4306737). To the same plate, add each of the cDNA diluted X10 and X100 with HaCaT cDNA 2 // «and Easy Dilution (Kit code RR037A, Lot A1201-1) to prepare the standard curve.
  • the cDNA prepared above was added to the reaction solution and reacted with real-time PCR Cycles.
  • Real-time PCR reactions were first repeated samples at 94 0 C, 10 minutes for initial denaturation and then amplified a total of 60 cycles.
  • the time and temperature for each cycle consisted of 10 seconds at 94 0 C, 10 seconds at 60 ° C., and 30 seconds at 25 ° C.
  • the capture Ab diluted in coating buffer was added at 100
  • Nutritional lotion in the cosmetic solution containing a solution of Example 2 was prepared in the composition shown in Table 6.
  • Cosmetic cream containing the solution of Example 2 was prepared in the composition shown in Table 7.
  • a massage cream in the cosmetic composition containing the solution of Example 2 was prepared in the composition of Table 8 below.
  • the cosmetics of Formulation Example 2 and Comparative Formulation Example 2 were used to evaluate the improvement of itching. Forty patients who had severe skin itch due to atopic dermatitis, eczema, urticaria, and sea layer, no other systemic diseases, and no oral antibiotics and immunosuppressants in recent months were selected. The cause of the itch was not distinguished, and only the degree of feeling of itching was selected based on the intensity of the initial five or more. The ages ranged from 20 to 45 years. The average age was 31.5 years old. There were 23 men and 17 women. Patients did not use topical steroids within a week prior to the start of the study and restricted the use of topical steroids during the study.
  • the degree of itching (pruritus) after 30 minutes and 1 hour after the application of the sample prepared by Comparative Example 2 to the site defined as the affected part of the nutrition cream prepared according to Formulation Example 2 and Comparative Example 2 of Formulation Example 2 was quantified according to subjective judgment, and then the sample prepared by Formulation Example 2 was applied to the same site once to quantify the degree of itching (pruritus) for 30 hours at three-minute intervals according to subjective judgment.
  • the itch relief assessment divided the intensity of the itch by a number between 1 and 10 to indicate the intensity of the itch that is currently felt.
  • the average value (% itch activity) obtained by dividing the intensity value obtained with each time by dividing the initial intensity value by a percentage is shown in Table 11 below with time. In addition, the results are shown in FIG.
  • Formulation Example 3 Clinical evaluation of the atopic skin improvement effect on the cosmetic formulation of Formulation Example 3 was measured.
  • Formulation Example 3 In order to evaluate the effect of improving the atopic skin of the cosmetics, the following experiment was conducted on 15 patients who were treated by atopic skin. The test sample was applied to the whole body by dividing the right side and the left side by the double-blinded test, but the use of other moisturizers that could affect the effect of the test sample was prohibited as much as possible. The effects after 1, 2, 3, and 4 weeks of application of the test sample were calculated according to Equation 1 by SCORAD (SCORAD: SCORing Atopic Dermatitis) measurement and the results are shown in Table 11 below.
  • SCORAD SCORAD: SCORing Atopic Dermatitis
  • Taekwondo degree (1/2 ⁇ 3)

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Abstract

La présente invention concerne une composition cosmétique pour inhiber et soulager le prurit ou soulager la dermatite atopique, contenant, en tant que substance active, de l'isosécotanapartholide représenté par la formule chimique [1] ci-dessous. Selon la présente invention, la composition cosmétique contenant de l'isosécotanapartholide est très sûre étant donné qu'aucune cytotoxicité n'a été observée, est capable d'inhiber et de soulager le prurit par inhibition de l'interleukine 31 (IL-31) ou l'interleukine 33 (IL-33) parmi les cytokines causant différents types de prurit, a une excellente capacité d'inhibition d'une cytokine lymphopoïétine stromale thymique (TSLP), qui est la protéine de niveau supérieur dans une signalisation anormale causée par un déséquilibre immunitaire, qui est la cause fondamentale de dermatite atopique, et a une excellente capacité d'inhibition de l'expression des chimiokines MDC et TARC dans des cellules HaCaT et, par conséquent, la composition cosmétique peut soulager la peau atopique.
PCT/KR2016/005534 2015-05-26 2016-05-25 Composition cosmétique pour inhiber le prurit et soulager la dermatite atopique, contenant de l'isosécotanapartholide en tant que substance active Ceased WO2016190661A1 (fr)

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KR102642582B1 (ko) 2021-06-01 2024-03-04 주식회사 제이투케이바이오 동백나무꽃, 쑥잎 및 영지버섯 혼합추출물을 유효성분으로 함유하는 항산화, 항염, 항알러지용 화장료 조성물
CN115073400B (zh) * 2022-06-10 2024-04-05 河南中医药大学 具有降糖活性1,10位-裂环的愈创木内酯倍半萜类化合物的制备方法及其应用

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* Cited by examiner, † Cited by third party
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WO2022101932A1 (fr) * 2020-11-10 2022-05-19 Institute Of Bioresources And Sustainable Development Nouvelle composition de biofumigant et son procédé de préparation
CN114028296A (zh) * 2021-12-13 2022-02-11 上海宜侬生物科技有限公司 一个多维度修护皮肤敏感的化妆品成分与应用

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