CN115487108A - Caspase-1 activity inhibitor with antioxidant activity and application thereof - Google Patents
Caspase-1 activity inhibitor with antioxidant activity and application thereof Download PDFInfo
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- CN115487108A CN115487108A CN202211132186.7A CN202211132186A CN115487108A CN 115487108 A CN115487108 A CN 115487108A CN 202211132186 A CN202211132186 A CN 202211132186A CN 115487108 A CN115487108 A CN 115487108A
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- caspase
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- inhibitor
- antioxidant activity
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 108010089193 pattern recognition receptors Proteins 0.000 description 1
- 102000007863 pattern recognition receptors Human genes 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 230000036620 skin dryness Effects 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
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
- A61K8/96—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
- 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
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Dermatology (AREA)
- Medicines Containing Plant Substances (AREA)
- Cosmetics (AREA)
Abstract
The invention relates to the technical field of cosmetics, in particular to the field of IPC A61K, and more particularly relates to a caspase-1 activity inhibitor with antioxidant activity and application thereof. The caspase-1 activity inhibitor with antioxidant activity at least comprises kunzea extracting solution. The Carneancard extracting solution which is a caspase-1 activity inhibitor with antioxidant activity is prepared, can inhibit the activation of caspase-1, has a certain antioxidant effect, and can inhibit the formation of inflammatory corpuscles by eliminating free radicals. The caspase-1 activity inhibitor with antioxidant activity prepared by the application can be applied to cosmetics, and can inhibit skin injury such as inflammation and dryness and skin aging caused by external factors such as ultraviolet rays.
Description
Technical Field
The invention relates to the technical field of cosmetics, in particular to the field of IPC A61K, and more particularly relates to a caspase-1 activity inhibitor with antioxidant activity and application thereof.
Background
In recent years, a protein complex called "inflammasome" has attracted attention, which is a major causative factor of inflammatory reactions of the skin. The inflammasome consists of NOD-like receptor (NLR) family proteins such as NLRC4, NLRP1, NLRP3, etc., or pattern recognition receptors such as AIM2 (melanoma-deficient factor 2), and the precursors of adaptor protein ASC (apoptosis-related microprotein containing Caspase recruitment domain) and Caspase-1 (Caspase-1). When exposed to external factors such as ultraviolet rays or bacteria, NLRC4, NLRP1, NLRP3, and AIM2 form inflammatory corpuscles in cells, thereby activating caspase-1. Activated caspase-1 can promote the activation of proinflammatory cytokines such as IL-1 beta and IL-18, etc., which are the main cause of skin roughness, and therefore, it is required to develop an effective ingredient capable of inhibiting inflammatory bodies, which can be applied to cosmetics.
In the prior art, japanese patent application laid-open No. 2018-080186 proposes that a plant extract such as burdock can inhibit caspase-1 activation, but does not mention the inhibitory effect of other extracts on caspase-1 activation. Chinese patent application No. CN201610548372.7 discloses topical skin care preparations containing plant extracts, but does not mention the inhibitory effect and antioxidant effect of the extracts on caspase-1 activation, and the use of the extracts as cosmetic active ingredients.
Disclosure of Invention
In order to solve the above problems, according to a first aspect of the present invention, there is provided a caspase-1 activity inhibitor having antioxidant activity, the caspase-1 activity inhibitor having antioxidant activity comprising at least kunzea extracting solution.
The preparation method of the kunzea extracting solution comprises the following steps:
washing the raw materials with water, removing impurities, drying, pulverizing, mixing the pulverized raw materials with a solvent, and extracting to obtain Carneaka extractive solution.
The raw material is Carneaka, and the preferred application part is Carneaka leaf.
The Carneaus card is a Carneaus card (Kunzaearicosides) of a plant of the genus Thamnolia (Kunzea) of the family Myrtaceae (Myrtaceae).
The solvent includes, but is not limited to, one or more of water, lower alcohol solvents, polyol solvents, ester solvents, ketone solvents, ether solvents, and hydrocarbon solvents.
The lower alcohols include, but are not limited to, one or more of methanol, ethanol, and propanol.
The polyols include, but are not limited to, one or more of ethylene glycol, propylene glycol, 1, 3-butylene glycol, and glycerol.
The lipids include, but are not limited to, one or more of ethyl acetate, butyl acetate, and methyl propionate.
The ketones include, but are not limited to, one or more of acetone, methyl ethyl ketone.
The ethers include but are not limited to one or more of diethyl ether and isopropyl ether.
The hydrocarbon solvent includes, but is not limited to, n-hexane.
More preferably, the solvent is a mixture of water and ethanol (aqueous ethanol solution) or a mixture of water and 1, 3-butanediol (aqueous 1, 3-butanediol solution).
In the mixed liquid of the water and the 1, 3-butanediol, the mass percent of the 1, 3-butanediol is 10-70 w/w%.
In the mixed liquid of water and ethanol, the mass percent of the ethanol is 10-60 w/w%.
The extraction method includes but is not limited to a dipping method.
In some preferred embodiments, the extraction method comprises: filtering after soaking to obtain coarse extractive solution of Carneaka; concentrating the crude Carneaka extract under reduced pressure to obtain Carneaka concentrated solution; adding solvent into Carneaka concentrated solution, and adjusting pH value to obtain the final product.
In the extraction process, there is no particular limitation on the pH.
In some preferred embodiments, the pH is adjusted to 3 to 9; further preferably, the pH is adjusted to 3.5 to 5.5.
The method for adjusting the pH value is to add alkaline regulators such as sodium hydroxide, sodium carbonate, potassium hydroxide and the like or acidic regulators such as citric acid, hydrochloric acid, phosphoric acid, sulfuric acid and the like.
In the extraction process, the extraction temperature is 0-80 ℃, and the extraction time is 1-168 h.
The Carneaka extracting solution can be used for obtaining a final product by methods of pH value adjustment, vacuum concentration, spray drying and the like; the product can be directly used as a cosmetic raw material.
In a second aspect, the present invention provides use of the inhibitor of caspase-1 activity having antioxidant activity, which can be applied to cosmetics including, but not limited to, lotions, creams, lotions, essences, masks, lipsticks, foundations, masks, foundation solutions, pressed powders, blushes, white powders and facial washes, body washes, shampoos, soaps, hair tonics, body washes, and the like.
When the caspase-1 activity inhibitor with antioxidant activity prepared by the invention is applied to preparations (cosmetics and the like), the preparations can be compounded with any components. Illustrative examples of the component (a) include hydrocarbons such as squalane, vaseline, and microcrystalline wax; esters such as jojoba oil, carnauba wax, and octyldodecanol oleate; triglycerides such as olive oil, beef tallow, coconut oil, etc.; fatty acids such as stearic acid, oleic acid, and retinoic acid; higher alcohols such as oleyl alcohol, stearyl alcohol and octyldodecanol; anionic surfactants such as sulfosuccinates and sodium polyoxyethylene alkyl sulfates; amphoteric surfactants such as alkyl betaines; cationic surfactants such as dialkyl ammonium salts; nonionic surfactants such as sorbitol fatty acid esters, monoglycerol fatty acid esters, polyoxyethylene adducts of these sorbitol fatty acid esters, polyoxyethylene adducts of monoglycerol fatty acid esters, polyoxyethylene alkyl ethers, and polyoxyethylene esters of fatty acids; polyhydric alcohols such as polyethylene glycol, glycerin, and 1, 3-butanediol; a thickener such as beta-glucan, an ultraviolet ray protective agent such as a gelling agent, an antioxidant, an ultraviolet ray absorber or an ultraviolet ray scattering agent, a coloring agent, a preservative, a pH adjusting agent, a powder, an active substance such as dipotassium glycyrrhizinate, hyaluronic acid or a salt thereof, hydroxyppinacolone retinoic acid ester, a plant extract such as an extract of centella asiatica, a culture solution of bifidobacterium, and other microbial components.
Has the advantages that:
1. the Carneaka extracting solution which is the caspase-1 activity inhibitor with antioxidant activity is prepared, can inhibit the activation of caspase-1, has a certain antioxidant effect, and can inhibit the formation of inflammatory bodies by eliminating free radicals.
2. The caspase-1 activity inhibitor with antioxidant activity, prepared by the method, is applied to cosmetics, and can inhibit skin injury such as inflammation and dryness and skin aging caused by external factors such as ultraviolet rays.
Detailed Description
The present invention is described in detail below with reference to examples, which are provided for the purpose of further illustration only and are not to be construed as limiting the scope of the present invention, and the insubstantial modifications and adaptations thereof by those skilled in the art based on the teachings of the present invention will still fall within the scope of the present invention. All the following parts are parts by weight and% are% by weight.
Example 1
Example 1 provides a caspase-1 activity inhibitor with antioxidant activity, which is kunzaka extract.
The preparation method of the kunzea extracting solution comprises the following steps:
drying and crushing kunzea leaves to obtain 300g of crushed product, mixing the crushed product with 1500g of 20% ethanol water solution, soaking at 40 ℃ for 2 hours, and filtering to obtain 1300g of kunzea crude extract; concentrating the coarse kaneca extract under reduced pressure to obtain 1040g of a kaneca concentrated solution; to the cananca concentrated solution, a 1, 3-butanediol aqueous solution was added to a concentration of 1, 3-butanediol of 30% to obtain 16.2kg of an extract of cananca (solid content 0.20%).
Example 2
Example 2 provides a caspase-1 activity inhibitor having antioxidant activity, and the specific embodiment is the same as example 1, except that:
300g of 50% aqueous ethanol was used instead of 20% aqueous ethanol, to obtain 16.4kg of kaneca extract (solid content: 0.21%).
Performance test method
In the evaluation tests of the following performance test methods 1 to 3, the effect of protein complexes (inflammasome) which are substances involved in the production of proinflammatory cytokines was evaluated. Caspase-1 can be activated due to the formation of inflammatory bodies, and caspase-1 can in turn cause further activation of pro-inflammatory cytokines (IL-1. Beta., IL-18, etc.), which are thereby released outside the cell, leading to the development of inflammation.
In the performance test methods 1 to 3, the activity evaluation test of the caspase-1 activity inhibitor having antioxidant activity prepared in the present invention on caspase-1 in cells, the evaluation test of the effect of inhibiting the production of proinflammatory cytokines, and the evaluation test of the increase in the expression level of filaggrin 2 (natural moisturizing factor) decreased due to the formation of inflamed bodies were performed using a substance (lipopolysaccharide) inducing the formation of inflamed bodies and an environmental factor (ultraviolet light).
1. Evaluation test of intracellular caspase-1 Activity
Experiments were performed with normal human skin fibroblasts (NB 1 RGB). Inoculate 9.0X 10 per well in 24-well plates 4 And (4) one cell. The caspase-1 activity inhibitors having antioxidant activity of example 1 (final concentrations of the activity inhibitors in the culture solution were 0.5% (test group 1), 1.0% (test group 2), and 2.0% (test group 3)) were added to the culture solution (type: eagle MEM; manufacturer: nikkiso Co., ltd.) to prepare sample solutions, and the cells were cultured in the culture solutions for one day. After the culture, lipopolysaccharide (manufacturer: invitrogen) was added to the culture system at a concentration of 1.0. Mu.g/mL, and the culture was continued for 1 hour, followed by irradiation at 100mJ/cm 2 Dosage of Ultraviolet (UV)-B), culture was continued for 4h, inducing the formation of inflamed bodies and thus activating caspase-1. In addition, control 1 and Control 2 were also provided, and 30% of 1, 3-butanediol aqueous solution (Control (1, 3-BG)) was added to each of Control 1 and Control 2 in place of the caspase-1 activity inhibitor having an antioxidant activity in example 1, and Control 1 was not subjected to ultraviolet irradiation.
After completion of the culture, the cultured cells were stained with Pyropolsis/Caspase-1 assay kit (manufacturer: immunochemistry technologies Co.) and subjected to flow cytometry (model: BD Accuri) TM C6 Plus Flow Cytometer; the manufacturer: bifid medical corporation, usa) measured the amount of fluorescence (Ex =488nm, em =533 ± 15 nm). The rate of caspase-1 activity in the cells was calculated using the amount of fluorescence value of control group 2 as 100%, and the results are shown in Table 1.
TABLE 1 Effect of intracellular caspase-1 Activity
| Test specimen | Whether or not to irradiate ultraviolet rays | Concentration of | Caspase-1 Activity Rate (%) | |
| Control group 1 | Control(1,3-BG) | Non-irradiated ultraviolet ray | - | 76.2 |
| Control group 2 | Control(1,3-BG) | Irradiating ultraviolet rays | - | 100.0 |
| Test group 1 | The product of example 1 | Irradiating ultraviolet rays | 0.5％ | 85.0 |
| Test group 2 | The product of example 1 | Irradiating ultraviolet rays | 1.0％ | 79.1 |
| Test group 3 | The product of example 1 | Irradiating ultraviolet rays | 2.0％ | 78.7 |
As shown in table 1, the extractive solution of kunzea, which is an inhibitor of caspase-1 activity having antioxidant activity, of the present invention can inhibit the activity of caspase-1, and has a better inhibitory effect on caspase-1 as the concentration increases, indicating that the activity of caspase-1 can be inhibited by the extractive solution of kunzea of the present invention under the stimulation of external environmental factors (ultraviolet rays, bacteria, etc.).
2. Evaluation test of Effect of suppressing production of proinflammatory cytokine
Normal human dermal fibroblasts (NB 1 RGB) were cultured in the same manner as described in "Performance test method 1 and evaluation test of intracellular caspase-1 Activity". After UV-B irradiation for 48 hours, culture supernatants were collected, and proinflammatory cytokines were quantitatively detected using IL-1 β ELISA kits (model: IL-1 β Human ELISA Kit RSD-DLB50-1; manufacturer: R & D Systems, inc.) and IL-18ELISA kits (model: human Total IL-18/IL-1F4 ELISA Kit RSD-DL180-1; manufacturer: R & D Systems, inc.), respectively. And the respiratory activity of the cells was measured by MTT reduction. That is, 0.03% of MTT was added, the mixture was held at 37 ℃ for 1 hour, the formazan thus formed was extracted with isopropanol, the MTT value was measured at a wavelength of 570 to 630nm using a microplate reader (Model 680; manufacturer: bio-Rad), the MTT value was divided by the amount of each cytokine to obtain the amount of cytokine per MTT, the value of control group 2 was set to 100, and the production rate of proinflammatory cytokine was calculated, and the results are shown in tables 2 and 3.
TABLE 2 Productivity of proinflammatory cytokine IL-18
| Test specimen | Whether or not to irradiate ultraviolet rays | Concentration of | 1L-18 production Rate (%) | |
| Control group 1 | Control(1,3-BG) | Non-irradiated ultraviolet ray | - | 23.6 |
| Control group 2 | Control(1,3-BG) | Irradiating ultraviolet rays | - | 100.0 |
| Test group 1 | Extract of example 1 | Irradiating ultraviolet rays | 0.5％ | 93.7 |
| Test group 2 | Extract of example 1 | Irradiating ultraviolet rays | 1.0％ | 91.5 |
| Test group 3 | Extract of example 1 | Irradiating ultraviolet rays | 2.0％ | 86.5 |
TABLE 3 production Rate of proinflammatory cytokine IL-1 β
| Test specimen | Whether or not to irradiate ultraviolet rays | Concentration of | 1L-1. Beta. Production Rate (%) | |
| Control group 1 | Control(1,3-BG) | Non-irradiated ultraviolet ray | - | 20.1 |
| Control group 2 | Control(1,3-BG) | Irradiating ultraviolet rays | - | 100.0 |
| Test group 1 | Extract of example 1 | Irradiating ultraviolet rays | 0.5％ | 89.5 |
| Test group 2 | Extract of example 1 | Irradiating ultraviolet rays | 1.0％ | 82.9 |
| Test group 3 | Extract of example 1 | Irradiating ultraviolet rays | 2.0％ | 79.7 |
As shown in tables 2 and 3, carneancard extract, an inhibitor of caspase-1 activity having antioxidant activity in the present invention, was able to inhibit the production of proinflammatory cytokines (IL-18, IL-1. Beta.). Therefore, the kunzea extracting solution prepared by the invention has excellent anti-inflammatory effect. In addition, IL-1 beta is also a SASP factor for inducing aging, so the catancard extract prepared by the invention also has excellent anti-aging effect.
3. Evaluation test of expression of filaggrin 2 (Natural moisturizing factor)
Experiments were performed using normal human epidermal cells (NHEK). 6.0X 10 inoculations per well in 24-well plates 4 A cell; after one day of culture, five groups of culture supernatants of Performance test method 2 were added as samples, and after further culturing for 24 hours, each cell was recovered with 500. Mu.L of Trizol reagent (manufacturer: invitrogen); adding 100 μ L chloroform into the recovered cells, stirring, mixing, centrifuging at 12500rpm and 4 deg.C for 15min, and collecting 200 μ L water layer; adding 250 μ L isopropanol into the recovered water layer, stirring, mixing, and centrifuging at 12500rpm and 4 deg.C for 10min to obtain total RNA precipitate; adding 1mL of 75% cold ethanol into total RNA, stirring, cleaning, centrifuging at 12500rpm and 4 ℃ for 10min, and recovering precipitate; the collected precipitates were subjected to reverse transcription reaction using a predetermined Kit (model: primeScript RT reagent Kit with gDNA Eraser (Perfect Real Time); manufacturer: takara-bio Co., ltd.) to synthesize cDNA; using the synthesized cDNA as a sample, the expression of the target gene (filaggrin-2 gene) and the expression of the internal standard GAPDH gene were examined using Thermal Cycler Dice Time System Single (manufacturer: takara-bio), and SYBR Premix Ex TaqTM II (manufacturer: takara-bio). The relative expression level of the target gene (filaggrin 2 gene: FLG 2) to the GAPDH gene was calculated as the test result, and the result is shown in Table 4 with the control group 2 as 100 and the relative ratio.
TABLE 4 expression rate of filaggrin 2 (Natural moisturizing factor)
| Test specimen | Whether or not to irradiate ultraviolet rays | Concentration of | FLG2 expression Rate (%) | |
| Control group 1 | Control(1,3-BG) | Non-irradiated ultraviolet ray | - | 144.5 |
| Control group 2 | Control(1,3-BG) | Irradiating ultraviolet rays | - | 100.0 |
| Test group 1 | Extract of example 1 | Irradiating ultraviolet rays | 0.5％ | 115.1 |
| Test group 2 | Extract of example 1 | Irradiating ultraviolet rays | 1.0％ | 118.9 |
| Test group 3 | Extract of example 1 | Irradiating ultraviolet rays | 2.0％ | 128.4 |
As shown in table 4, it is shown that the kunzea extract solution, which is an inhibitor of caspase-1 activity having an antioxidant activity, can increase the expression rate of the natural moisturizing factor filaggrin 2 (FLG 2) after uv fiber irradiation, and thus it is considered that the kunzea extract solution can inhibit the problem of skin dryness caused by inflammation due to uv light.
4. Evaluation test for DPPH (1, 1-Diphenyl-2-picrylhydrazyl, 1-Diphenyl-2-picrylhydrazyl) radical scavenging
A DPPH solution is prepared by dissolving 2.4 parts of DPPH in 20 parts of ethanol, and adding 20 parts of water thereto. An additive DPPH solution was prepared by adding 19.2 parts of an 18v/v% ethanol aqueous solution and 4.8 parts of a 2M acetic acid-sodium acetate buffer (pH 5.5) to 24 parts of the DPPH solution. In order to reduce the effect of the color of the Carneaka extract solution itself on the test, a solution of 50v/v% ethanol in water was used instead of DPPH, and an 18v/v% ethanol in water was mixed with 2M acetic acid-sodium acetate buffer solution as a control solution. Then, the kaneca extract solution obtained in example 1 was diluted with water to prepare sample solutions in which the volume concentrations of the kaneca extract solution were 0.5% (test group 1), 1.0% (test group 2), and 2.0% (test group 3), respectively. The sample solution was mixed with the DPPH additive solution and the control solution at a weight ratio of 1.
Meanwhile, the same procedure as described above was carried out using water instead of the sample solution as a control group, and the relative values of the residual ratio of DPPH radicals at the time of adding each sample and the residual ratio of DPPH radicals obtained therefrom were obtained, and the results are shown in table 5.
TABLE 5 DPPH radical scavenging evaluation
| Test specimen | Concentration of | DPPH radical residual ratio (%) | |
| Control group | Water (W) | - | 100 |
| Test group 1 | The product of example 1 | 0.5％ | 38.9 |
| Test group 2 | The product of example 1 | 1.0％ | 41.5 |
| Test group 3 | The product of example 1 | 2.0％ | 33.1 |
As shown in table 5, the extractive solution of kunzea in the present invention has excellent DPPH radical scavenging effect, thereby showing that it also has a certain antioxidant effect. Free radicals promote the formation of inflammatory bodies, so that the kunzea extracting solution with the antioxidant effect can inhibit the formation of inflammatory bodies, and therefore activation of caspase-1 is inhibited.
5. Evaluation test for erythema inhibition
In accordance with the formulation ingredients in table 6, a lotion (sample 1) containing the kunzea extract solution prepared in example 1 and a lotion (comparative example 1) prepared by substituting 30% of a 1, 3-butanediol aqueous solution (30% of 1, 3-BG) for the kunzea extract solution prepared in example 1 were prepared.
TABLE 6 toning lotion formulation
| Composition (I) | Sample No. 1 | Comparative example 1 |
| Extract of example 1 | 0.5％ | - |
| 30％1,3-BG | - | 0.5％ |
| 1,3-BG | 5.0％ | 5.0％ |
| Esters of p-hydroxybenzoic acid | 0.2％ | 0.2％ |
| Water (W) | 94.3％ | 94.3％ |
The two test specimens shown in table 6 were applied to the test site on the left forearm of each subject twice a day for one week, and then the erythema index (initial value) of each test area was measured by a Mexameter, followed by ultraviolet irradiation treatment at 1 biological dose (1 MED) for each subject. After one day, the erythema index of each test area was also measured using a Mexameter, and the ratio of the change of this value to the initial value was calculated. The erythema rates of sample 1 and the non-applied area were calculated using the measurement results of the applied area of comparative example 1 as 100, and the results are shown in table 7.
TABLE 7 erythema Rate test results
| Test area | Percentage of erythema (%) |
| No smearing zone | 94.2 |
| Application area of comparative example 1 | 100.0 |
| Smear zone of sample 1 | 81.9 |
As shown in table 7, when the application area of sample 1 prepared by the present invention was compared with the application area and the non-application area of comparative example 1, it was revealed that the kunca extract solution prepared by the present invention had an effect of inhibiting erythema when applied to cosmetics.
The following is an example of cosmetics containing the kunzea extract solution prepared according to the present invention, and the kunzea extract solution prepared according to the present invention is applicable to all cosmetics.
Formulation 1 cosmetic: the formula of the cosmetic comprises the following components in percentage by weight: carneancard extract solution prepared in example 1 was 0.5%, β -glucan 0.5%, dipotassium glycyrrhizinate 0.2%, 1, 3-butylene glycol 1.0%, sodium citrate 0.05%, and water to make up the balance to 100%.
Formulation 2 cosmetic product: the formula of the cosmetic comprises the following components in percentage by weight: 2.0% of Carneauca extract prepared in example 1, 0.05% of hydroxyppinacolone retinoic acid ester, 0.1% of Bifidobacterium culture, 0.1% of 1, 3-butanediol, 0.5% of phenoxyethanol, 0.05% of sodium citrate, and the balance of water to 100%.
Formulation 3 cosmetic: the formula of the cosmetic comprises the following components in percentage by weight: carnean extract solution prepared in example 1 was 2.0%, centella asiatica extract was 0.2%, sodium hyaluronate was 0.8%, 1, 3-butylene glycol was 0.1%, phenoxyethanol was 0.5%, sodium citrate was 0.05%, and the balance of water was 100%.
Claims (10)
1. A caspase-1 activity inhibitor with antioxidant activity, characterized in that the caspase-1 activity inhibitor with antioxidant activity at least comprises kunzea extracting solution.
2. The caspase-1 activity inhibitor with antioxidant activity according to claim 1, wherein the preparation method of kunzea extract comprises the following steps: washing the raw materials with water to remove impurities, drying, crushing, mixing the crushed raw materials with a solvent, and extracting to obtain a Carneaka extracting solution; the raw material is Carneaka.
3. The caspase-1 activity inhibitor with antioxidant activity according to claim 2, wherein the preferred site of use of kunzea is kunzea leaf.
4. A caspase-1 activity inhibitor with antioxidant activity according to claim 3, wherein said solvent includes but not limited to one or more of water, lower alcohol solvent, polyol solvent, ester solvent, ketone solvent, ether solvent, hydrocarbon solvent.
5. The inhibitor of caspase-1 activity with anti-oxidant activity according to claim 4, wherein the solvent is a mixture of water and ethanol or a mixture of water and 1, 3-butanediol.
6. The caspase-1 inhibitor with antioxidant activity according to claim 5, wherein the mass percentage of 1, 3-butanediol in the mixture of water and 1, 3-butanediol is 10-70 w/w%.
7. The caspase-1 inhibitor with antioxidant activity according to claim 5, wherein the mass percentage of ethanol in the mixture of water and ethanol is 10-60 w/w%.
8. The caspase-1 inhibitor with antioxidant activity according to claim 7, wherein the extraction temperature is 0-80 ℃ and the extraction time is 1-168 h.
9. The inhibitor of caspase-1 activity with antioxidant activity according to claim 8, wherein said extraction method comprises but is not limited to dipping method.
10. Use of the caspase-1 activity inhibitor with antioxidant activity according to any one of claims 1-9 in cosmetics.
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| CN202211132186.7A CN115487108A (en) | 2022-09-16 | 2022-09-16 | Caspase-1 activity inhibitor with antioxidant activity and application thereof |
| PCT/CN2023/079642 WO2024055536A1 (en) | 2022-09-16 | 2023-03-03 | Caspase-1 activity inhibitor having antioxidant activity and use thereof |
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| CN202211132186.7A CN115487108A (en) | 2022-09-16 | 2022-09-16 | Caspase-1 activity inhibitor with antioxidant activity and application thereof |
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|---|---|---|---|---|
| WO2024055536A1 (en) * | 2022-09-16 | 2024-03-21 | 上海优萃生物科技有限公司 | Caspase-1 activity inhibitor having antioxidant activity and use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103458908A (en) * | 2010-12-28 | 2013-12-18 | 玫琳凯有限公司 | Sebum control and anti-acne composition |
| CN106074278A (en) * | 2010-09-09 | 2016-11-09 | 玫琳凯有限公司 | Comprise the topical skin care preparation of plant extract |
| JP2022124984A (en) * | 2021-02-16 | 2022-08-26 | ビーエイチエヌ株式会社 | Lipase activity inhibitor and use thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103284897B (en) * | 2012-01-27 | 2018-02-09 | 玫琳凯有限公司 | Cosmetic formulations |
| US8877259B2 (en) * | 2012-02-09 | 2014-11-04 | Mary Kay Inc. | Cosmetic formulation |
| CN110141541B (en) * | 2019-06-17 | 2022-04-08 | 广州环亚化妆品科技有限公司 | Dandruff-removing itching-relieving scalp conditioning liquid and preparation method and application thereof |
| CN115487108A (en) * | 2022-09-16 | 2022-12-20 | 上海优萃生物科技有限公司 | Caspase-1 activity inhibitor with antioxidant activity and application thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074278A (en) * | 2010-09-09 | 2016-11-09 | 玫琳凯有限公司 | Comprise the topical skin care preparation of plant extract |
| CN103458908A (en) * | 2010-12-28 | 2013-12-18 | 玫琳凯有限公司 | Sebum control and anti-acne composition |
| JP2022124984A (en) * | 2021-02-16 | 2022-08-26 | ビーエイチエヌ株式会社 | Lipase activity inhibitor and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| SINEMOBONG O ESSIEN等: "The antibacterial and antiproliferative ability of kānuka, Kunzea ericoides, leaf extracts obtained by subcritical water extraction", J CHEM TECHNOL BIOTECHNOL, vol. 96, pages 1308 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024055536A1 (en) * | 2022-09-16 | 2024-03-21 | 上海优萃生物科技有限公司 | Caspase-1 activity inhibitor having antioxidant activity and use thereof |
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