Preparation and application of a supramolecular composition with moisturizing and soothing efficacy

Abstract

This invention relates to the technical field of cosmetics, and discloses the preparation and application of a supramolecular composition with moisturizing and soothing effects. Using extracts of kava (PIPER METHYSTICUM) leaf / root / stem, milk thistle (SILYBUM MARIANUM) extract, and oat (AVENA SATIVA) extract as core active ingredients, supramolecular encapsulation and spray drying technologies are employed to encapsulate these poorly soluble soothing active ingredients with an encapsulation material. This solves the technical pain points of poor solubility, low transdermal absorption efficiency, and easy loss of activity of single active ingredients. The encapsulated supramolecular composition can deeply penetrate to the basal layer of the skin, soothe damaged skin barrier, and synergistically exert a powerful moisturizing and soothing effect. When applied to cosmetics, it can nourish the skin from the inside out, replenish skin moisture, enhance skin barrier function, and help the skin restore a hydrated, radiant, smooth, and healthy state. Compared with existing single active ingredients, the supramolecular composition of the present invention has significant advantages such as high transdermal absorption efficiency, strong stability of active ingredients, and synergistic effect. It can be widely used in various skin care products such as creams, lotions, emulsions, and masks, as well as related cosmetic systems such as scalp care and body wash.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to a method for preparing a supramolecular composition with moisturizing and soothing effects and its application. Background Technology

[0002] Human skin is mainly composed of the epidermis, dermis, subcutaneous tissue, and accessory organs (sebaceous glands, sweat glands, etc.). It is an important and largest organ covering the entire body surface, possessing unique and independent functions. The epidermis determines the health and beauty of the skin, while the dermis contains abundant collagen and elastin fibers, making the skin both resilient and soft, providing nutrition and elasticity. The epidermis, from the surface to the basement, is further divided into the stratum corneum, stratum granulosum, stratum spinosum, and stratum basale. The texture, hydration, translucency, and protective function of the skin are largely determined by the stratum corneum. Simultaneously, the surface of the stratum corneum contains a slightly acidic natural sebum film, which moisturizes the skin, reduces moisture loss, and resists damage and invasion from harmful external substances. Once the stratum corneum sebum film is damaged, the skin will be unable to maintain normal physiological functions, leading to various skin problems. Furthermore, with age, the skin not only becomes dry and loose, but also develops pigmentation and wrinkles, and its ability to resist external stimuli decreases. In modern society, these skin changes are not unique to the elderly. Numerous factors constantly damage our skin, such as staying up late, prolonged computer use, smoking, air pollution, car exhaust, and UV exposure. These factors lead to a growing number of people experiencing fragile, sensitive, poor-quality, and intolerant facial skin with a damaged skin barrier. Therefore, skincare products that soothe damaged skin, enhance its resilience, and strengthen the skin barrier represent a long-term trend in the cosmetics industry.

[0003] However, most repair and soothing products on the market currently focus on strengthening the skin barrier and reducing skin sensitization when using other skincare and cosmetic products. These methods primarily address the skin's microecology, but they only improve skin problems caused by damage to the stratum corneum, acting only on epidermal cells. The supply of nutrients and the removal of metabolic waste from the skin mainly rely on the tissue fluid within the dermis traveling back and forth across the basement membrane, which cannot be achieved by acting solely on the epidermis. The basement membrane, located between the epidermis and dermis, is a crucial structure connecting them and is essential for targeted and precise skincare. Therefore, transdermal penetration is paramount for effective skincare.

[0004] The core active ingredient in kava lactone, found in the leaf, root, and stem extracts of PIPER METHYSTICUM, can specifically inhibit the activity of TRPV1 receptors in the skin, reduce the release of neuropeptides, and effectively relieve discomfort such as skin sensitivity, redness, and itching. However, it is a typical amphiphilic and poorly soluble component, with poor solubility in both water and oil phases, and low transdermal absorption efficiency, which limits its application in formulations.

[0005] Silymarin, the core active ingredient in milk thistle (Silybum marianum) extract, is a natural flavonoid compound with strong antioxidant and anti-inflammatory effects. It can inhibit the activation of the NF-κB signaling pathway, reduce the expression of inflammatory factors (such as IL-6 and TNF-α), alleviate skin inflammation, and promote skin barrier repair. However, it suffers from poor stability, water insolubility, poor lipid solubility, and low transdermal absorption.

[0006] The core active ingredient in oat (AVENA SATIVA) extract, dihydroagar alkaloids, can inhibit the release of histamine from mast cells induced by substance P, thereby soothing skin itching, redness, and improving skin sensitivity. However, it also suffers from poor stability, water insolubility, poor lipid solubility, and low transdermal absorption, further limiting its application in cosmetics.

[0007] Supramolecular inclusion technology is a novel technology in the cosmetics field in recent years. Its core lies in utilizing the cavity structure of inclusion materials to encapsulate active ingredients, effectively improving their solubility and stability, enhancing transdermal absorption efficiency, and reducing their irritation. However, inclusion technologies for different active substances often differ and are not universally applicable. Therefore, when multiple active substances need to be included, either an independent inclusion scheme is used to form inclusion compounds one by one, or the sensitivity of some components to heat, pH, etc., must be ignored, sacrificing the activity of these components or reducing their content to meet the inclusion scheme for a single process condition.

[0008] Therefore, it is urgent to explore how to overcome the contradictory requirements of different components in the encapsulation process and realize a process that can encapsulate multiple effective components at one time. Summary of the Invention

[0009] The present invention aims to overcome the above-mentioned defects by using supramolecular inclusion technology to encapsulate three poorly soluble active ingredients with different inclusion processes in a hydroxypropyl cyclodextrin material in a one-time encapsulation manner, thereby improving its solubility and permeability, allowing the active ingredients to reach the basal layer and exert their soothing effect. At the same time, since multiple groups of synergistic components are mixed in a single inclusion molecule, their highly efficient synergistic function is achieved.

[0010] Specifically, this invention provides a method for preparing a supramolecular composition with moisturizing and soothing effects and its application. By encapsulating extracts of kava (PIPER METHYSTICUM) leaves / roots / stems, milk thistle (SILYBUM MARIANUM) extract, and oat (AVENA SATIVA) extract in a supramolecular manner, it deeply repairs and soothes damaged skin, achieving a powerful moisturizing and soothing effect. When applied to cosmetic systems, it can nourish the skin from the inside out.

[0011] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a supramolecular composition with moisturizing and soothing effects, which is composed of active ingredients and inclusion materials; The ratio of active ingredient to inclusion material is 3.0–7.0: 93.0–97.0. The active ingredients are extracts of kava pepper, milk thistle, and oat.

[0012] Furthermore, the mass ratio of each component in the active ingredient—kava pepper extract, milk thistle extract, and oat extract—is (0.5–1.0):(0.5–1.0):(2.0–5.0).

[0013] Furthermore, the inclusion material is hydroxypropyl cyclodextrin with a degree of substitution of 0.8–1.5 and a molecular weight of 1100–1300 Da.

[0014] This invention also discloses a method for preparing the above-mentioned supramolecular composition. Through supramolecular inclusion and spray drying processes, the active ingredients are fully included, resulting in a stable inclusion complex. The specific steps are as follows: S1. Supramolecular inclusion: Take kava pepper extract, milk thistle extract, and oat extract respectively, mix them with hydroxypropyl cyclodextrin in a certain mass ratio, add ethanol, heat and stir to allow the active ingredient molecules to fully enter the cavity of hydroxypropyl cyclodextrin and form a stable inclusion solution. S2. Spray drying: The inclusion solution of the active ingredient is spray dried to obtain a supramolecular inclusion dry powder with stable activity; S3. Sieving: The obtained supramolecular inclusion dry powder is sieved through an 80-100 mesh sieve to obtain a stable supramolecular composition.

[0015] The supramolecular composition of the present invention can be widely used in moisturizing and soothing cosmetics as an active ingredient, with an addition amount of 0.5 to 8.0 wt%. It can be compounded with conventional cosmetic excipients (such as moisturizers, emulsifiers, preservatives, fragrances, deionized water, etc.) to prepare various dosage forms such as water, lotion, serum, cream, mask, gel, and gel, which are suitable for people with different skin types, especially sensitive skin and skin with damaged barrier.

[0016] Compared with the prior art, the present invention has the following beneficial effects: (1) Synergistic Effect: This invention selects three natural plant extracts as active ingredients. The core active ingredient, kavalactone, in the leaf / root / stem extract of Piper mestystium can specifically inhibit the activity of TRPV1 receptors in the skin, reduce the release of neuropeptides, and effectively relieve skin sensitivity, redness, itching, and other discomforts. The core active ingredient, silymarin, in the extract of milk thistle is a natural flavonoid compound with strong antioxidant and anti-inflammatory effects. It can inhibit the activation of the NF-κB signaling pathway, reduce the expression of inflammatory factors (such as IL-6 and TNF-α), alleviate skin inflammation, and promote skin barrier repair. The core active ingredient, dihydroagaric alkaloid, in the extract of avena sativa can inhibit the release of histamine from mast cells induced by substance P, thereby relieving skin itching, redness, and improving skin sensitivity. The three ingredients target different points, and after supramolecular inclusion, their synergistic effect is significantly enhanced, solving the problem of the single efficacy of existing single active ingredients.

[0017] (2) Improvement of application defects: The solubility of the three poorly soluble active ingredients is improved by supramolecular inclusion treatment of hydroxypropyl cyclodextrin, which solves the problems of poor solubility and low transdermal absorption rate; at the same time, the included active ingredients can achieve sustained and controlled release, increasing bioavailability.

[0018] (3) High transdermal absorption efficiency: The hydrophilic shell of hydroxypropyl cyclodextrin can promote the penetration of the inclusion complex into the stratum corneum of the skin and reach the basal layer of the skin through hair follicles, sebaceous glands and other pathways, thus solving the problem of low transdermal absorption efficiency of poorly soluble active ingredients.

[0019] (4) Wide range of applications: The supramolecular composition of the present invention has good hydrophilicity and good fluidity, and can be compatible with various cosmetic excipients. When the addition amount is 0.5 to 8.0 wt%, it can be used to prepare various moisturizing and soothing cosmetic systems such as water, lotion, essence, cream, and mask, without affecting the skin feel and stability of the product. It is suitable for people with different skin types, especially sensitive, barrier damaged and dry skin. Attached Figure Description

[0020] Figure 1 Graphical analysis of the comparison results between samples and blanks; Figure 2 A bar chart showing the a* values ​​of skin redness before and after use in the sample group; Figure 3 Bar chart showing skin hemoglobin index results before and after sample group use. Figure 4 Bar chart showing efficacy evaluation of the sample group after 4 weeks of use. Figure 5 Bar chart showing efficacy evaluation after 4 weeks of use in the control group. Figure 6 Bar chart showing user experience evaluation of the sample group after 4 weeks of use; Figure 7 Bar chart showing user experience evaluation after 4 weeks of use in the control group. Detailed Implementation

[0021] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] This embodiment provides a supramolecular composition with moisturizing and soothing effects, which consists of active ingredients (piper methistatum leaf / root / stem extract, milk thistle extract, oat extract) and inclusion material (hydroxypropyl cyclodextrin); the ratio of active ingredients to inclusion material is 3.0-7.0:93.0-97.0.

[0023] Based on some experimental examples, we found that when the proportion of active ingredients is too high (>7.0 parts) and the amount of encapsulating material is too low (<93.0 parts), there are often obvious unencapsulated free active substances, which appear cloudy, flocculent, and layered. In this case, the stability of the product's active ingredients decreases sharply, and even slight changes in light, temperature, and pH can lead to oxidation, decomposition, and discoloration, significantly shortening the product's shelf life. Simultaneously, unencapsulated active substances coming into direct contact with the skin can easily cause stinging, redness, and burning. Furthermore, excessive aggregation of active ingredients can lead to incompatibility with the cosmetic matrix, resulting in a coarse texture, oil-water separation, and a sticky feel.

[0024] In other experimental cases, we reduced the proportion of active ingredients, i.e., the proportion of active ingredients was low (<3.0 parts) and the proportion of encapsulation materials was high (>97.0 parts). As a result, the moisturizing and soothing effects were significantly insufficient and did not achieve the expected results. Even with complete encapsulation and good transdermal absorption, the overall bioavailability was still insufficient to produce significant effects.

[0025] This study found that the optimal synergistic effect of the three extracts was achieved when the mass ratio of active ingredients kava pepper extract, milk thistle extract, and oat extract was (0.5–1.0):(0.5–1.0):(2.0–5.0). Specifically, kava lactone, the core active ingredient in kava pepper (PIPER METHYSTICUM) leaf / root / stem extract, specifically inhibits the activity of skin TRPV1 receptors, reduces neuropeptide release, and effectively relieves skin sensitivity, redness, itching, and other discomforts. Silymarin, the core active ingredient in milk thistle (SILYBUM MARIANUM) extract, is a natural flavonoid compound with strong antioxidant and anti-inflammatory effects. It can inhibit NF-κB signaling pathway activation, reduce the expression of inflammatory factors (such as IL-6 and TNF-α), alleviate skin inflammation, and promote skin barrier repair. The core active ingredient in oat (AVENA SATIVA) extract, dihydroachyledin, can inhibit the release of histamine from mast cells induced by substance P, thereby soothing skin itching and redness and improving skin sensitivity. The combination of these three ingredients can exert moisturizing and soothing effects from different targets.

[0026] In some experimental cases, we adjusted the proportions of the three components and found that when the proportion of any one component was greater than or less than the above-mentioned ratio, the system became unstable. Specifically: When the proportions of kava pepper extract, milk thistle extract, or oat extract deviate from the set range, their synergistic effects in anti-inflammatory, repairing, and moisturizing properties are completely lost. For example, when the proportion of kava pepper extract is below 0.5, its calming and soothing effects are insufficient, failing to assist milk thistle extract in exerting its antioxidant damage-preventing effects; when the proportion of oat extract is above 5.0, its moisturizing and film-forming properties are too strong, which may mask the target sites of the other two active ingredients, resulting in an overall decrease in efficacy of more than 50%.

[0027] We found that, since the system in this embodiment is based on the one-step inclusion of multiple active ingredients, and the inclusion technologies of these active ingredient monomers are different, the compatibility requirements between the components are extremely high when they are mixed. When the proportion of any component is unbalanced, on the one hand, it will destroy the cavity structure of the inclusion material (such as cyclodextrin, liposomes) and the molecular matching degree of the active ingredient. For example, when the proportion of kava pepper extract or milk thistle extract is higher than 1.0, their molecular structures will compete with each other for inclusion sites, resulting in some active ingredients not being effectively encapsulated. The proportion of free components increases to more than 30%, which is easily affected by light and temperature and undergoes oxidative decomposition, shortening the half-life to 1 / 3 of the original. When the proportion of oat extract is lower than 2.0, its rich dietary fiber and polysaccharide components are insufficient to form a stable inclusion auxiliary system, resulting in a loose inclusion structure that is prone to dissociation in the cosmetic matrix. The release rate of active ingredients is out of control, which not only fails to achieve long-term effects, but may also cause irritation risks due to excessively high local concentrations.

[0028] During our research, we discovered that when the content of kava pepper extract and milk thistle extract exceeded the set values, an oil-water separation phenomenon occurred after standing. We speculate that this may be due to differences in the solubility and hydrophilicity / hydrophobicity of the three extracts. For example, kava pepper extract and milk thistle extract are more lipophilic, while oat extract is more water-soluble. Therefore, during the process of adjusting the balance, when the proportion of lipophilic components is too high (e.g., >1.0:1.0:5.0), it will lead to excessive lipophilicity of the system and a decrease in compatibility with water-soluble matrices (such as toners and serums). Hence, the oil-water separation phenomenon occurs after standing. Therefore, through numerous theoretical deductions and experimental attempts, we found that the balance point of these three components is a mass ratio of kava pepper extract, milk thistle extract, and oat extract of (0.5~1.0):(0.5~1.0):(2.0~5.0).

[0029] On the other hand, our study also found that if the proportion of oat extract is too high (e.g., >0.5:0.5:5.0), its polysaccharide components will aggregate excessively, leading to an abnormal increase in the viscosity of the system, and even forming a gel-like precipitate, which will damage the texture and appearance stability of the cosmetic.

[0030] On the other hand, our study also found that when the proportion of kava pepper extract is too high, its kava lactone components cannot be fully encapsulated, and the free components come into direct contact with the stratum corneum of the skin, which may cause redness and stinging. Similarly, when the proportion of milk thistle extract exceeds the optimal range, the oxidation products of its phenolic components will increase, and due to insufficient encapsulation, it is easy to penetrate into the deep layers of the skin, causing inflammatory stimulation to sensitive skin. When the proportion of oat extract is insufficient, its soothing and repairing components cannot form a protective film, which not only fails to alleviate the potential irritation of the other two components, but also causes local concentration fluctuations due to unstable encapsulation, further aggravating skin discomfort.

[0031] In this embodiment, the preferred degree of substitution of hydroxypropyl cyclodextrin is 0.8 to 1.5, and the molecular weight is 1100 to 1300 Da. The cavity size of hydroxypropyl cyclodextrin within this parameter range matches the molecular size of the three active ingredients and does not affect their synergistic effect. It has high inclusion efficiency and excellent hydrophilicity, which can improve the skin feel of the product.

[0032] In some experimental cases, we used hydroxypropyl cyclodextrin with a degree of substitution <0.8, such as 0.4-0.6. We found that the product had poor stability, was prone to layering or aggregation, and had high irritation. Based on the molecular structure, we believe this may be due to: First, insufficient hydroxypropyl substitution, resulting in low molecular polarity and steric hindrance, excessively tight cavity entrance, and a mismatch between the size of the active ingredient and the molecular size. This leads to insufficient inclusion driving force, making it difficult for guest molecules to enter or easy to detach, resulting in a significant decrease in inclusion rate and poor inclusion complex stability. Second, the hydrophilicity improvement is limited, and the water solubility is insufficient, which leads to easy turbidity, layering, and poor solubility and dispersibility of the system. Third, insufficient hydroxypropyl modification results in a strong tendency for cyclodextrin to crystallize, which easily precipitates in the formulation, making it sticky, astringent, and grainy. Fourth, insufficient space weakens the protective effect on sensitive active ingredients, making the product susceptible to light, heat, and oxidation, which in turn makes the active ingredients prone to degradation and inactivation.

[0033] In some experimental cases, we used molecules with a degree of substitution >1.5, such as 2.0-3.0. We found that excessive hydroxypropylation in these inclusion materials can lead to excessive side chains, excessively large molecular volume, steric hindrance that occupies cavities, and size mismatch with the active ingredient. Moreover, excessively hydrophilic molecules weaken hydrophobic inclusion interactions, resulting in inclusion compounds that are generally loosely structured, have low drug loading, and are prone to leakage. Furthermore, the high molecular weight increases the viscosity of the solution, leading to sticky, heavy, poorly absorbed products with noticeable residue.

[0034] This invention also discloses a method for preparing the above-mentioned supramolecular composition. Through supramolecular inclusion and spray drying processes, the active ingredients are fully included, resulting in a stable inclusion complex. The specific steps are as follows: S1. Supramolecular inclusion: Pepper METHYSTICUM leaf / root / stem extract, milk thistle (Silybum marianum) extract, and oat (AVENA SATIVA) extract were taken separately and mixed with hydroxypropyl cyclodextrin in a certain mass ratio. Ethanol was added, and the mixture was heated and stirred to allow the active ingredient molecules to fully enter the cavity of the hydroxypropyl cyclodextrin and form a stable inclusion solution. Hydroxypropyl cyclodextrin: 1 g ethanol : 3-5 mL (w / v); Total mass of extract: hydroxypropyl cyclodextrin 1:5-10 (w / w); Inclusion temperature: 45-55 ℃, preferably 50 ℃, and the temperature should not exceed 60 ℃ to avoid degradation of active ingredients such as calvalactone and silymarin.

[0035] The stirring speed is generally 200-400 rpm, and the incorporation time is 1-2 h, preferably 1.5 h at 50℃. After stirring, allow it to cool naturally to room temperature and let it stand for another 4-12 h to make the incorporation more stable.

[0036] S2. Spray drying: The inclusion solution of the active ingredient is spray dried to obtain a supramolecular inclusion dry powder with stable activity; S3. Sieving: The obtained supramolecular inclusion dry powder is sieved through an 80-100 mesh sieve to obtain a stable supramolecular composition.

[0037] The above-mentioned supramolecular composition is selected and applied as an active ingredient in moisturizing and soothing cosmetics. The addition amount is 0.5-8.0 wt%. It can be compounded with conventional cosmetic excipients (such as moisturizers, emulsifiers, preservatives, fragrances, deionized water, etc.) to prepare various dosage forms such as water, lotion, serum, cream, mask, gel, and gel, which are suitable for people with different skin types, especially sensitive skin and skin with damaged barrier.

[0038] The following will illustrate with selected experimental cases: Example 1. EffeMIX ® -HappyCalm A supramolecular composition with moisturizing and soothing effects, wherein the components are in the following parts by weight: 3.5 parts of active ingredients (0.5 parts of kava pepper leaf / root / stem extract, 1.0 part of milk thistle extract, 2.0 parts of oat extract), and 96.5 parts of hydroxypropyl cyclodextrin.

[0039] Preparation method: S01. Take 0.5 parts of kava leaf / root / stem extract, 1.0 part of milk thistle extract, and 2.0 parts of oat extract, respectively, and mix them with hydroxypropyl cyclodextrin according to the mass ratio. Add ethanol, heat and stir to obtain a supramolecular inclusion solution of active ingredients. S02. Spray dry the supramolecular inclusion solution obtained in step S01 to obtain supramolecular inclusion dry powder of active ingredients. S03. Pass the supramolecular inclusion dry powder obtained in step S02 through an 80-100 mesh sieve to obtain a stable supramolecular composition.

[0040] Example 2. Preparation of a soothing essence containing 1% EffeMIX®-HappyCalm.

[0041] (1) Weigh out the ingredients required for the soothing essence according to Table 1 below.

[0042] (2) The preparation method of the soothing essence is as follows: ① Mix the raw materials of phase A evenly and heat at 85°C until completely dissolved. ② Heat the raw materials of phase B at 85°C until completely dissolved. ③ Slowly add phase B to phase A and homogenize for 3-5 minutes. ④ Cool down to 60°C, add the raw materials of phase C in sequence, and stir evenly. ⑤ Cool down to 45°C, add the raw materials of phase D, and stir evenly to obtain the soothing essence.

[0043] Table 1 Soothing Essence Mutually Serial Number Raw material name W / W (%) A 1 Deionized water Up to 100 A 2 Acryloyldimethyltaurate / VP copolymer 0.50 A 3 Disodium EDTA 0.02 A 4 glycerin 5.00 A 5 Butylene glycol 3.00 B 6A Cetearyl alcohol olive oil ester 0.25 B 6B Sorbitan olive oil esters 0.25 B 7 Caprylic / Capric Triglyceride 5.00 B 8 Tocopheryl acetate 0.20 C 9 p-Hydroxyacetophenone 0.50 C 10 1,2-Hexanediol 0.50 D 11 <![CDATA[EffeMIX ® -HappyCalm]]> 1.00 .

[0044] Example 3. Preparation of an aqueous solution containing EffeMIX®-HappyCalm.

[0045] (1) Weigh the required raw materials according to Table 2 and Table 3.

[0046] (2) Stir to dissolve, and you will get 8% EffeMIX®-HappyCalm and 2% EffeMIX®-HappyCalm aqueous solution for later use.

[0047] Table 2 8% EffeMIX®-HappyCalm Solution Serial Number Raw material name W / W (%) 1 Deionized water 92.00 2 <![CDATA[EffeMIX ® -HappyCalm]]> 8.00 .

[0048] Table 3 2% EffeMIX®-HappyCalm Solution Serial Number Raw material name W / W (%) 1 Deionized water 98.00 2 <![CDATA[EffeMIX ® -HappyCalm]]> 2.00 .

[0049] Example 4. Efficacy Test 4.1 Safety Testing - Skin Patch Test Test substance: 8% EffeMIX obtained in Example 3® HappyCalm aqueous solution.

[0050] Negative control: filter The trial included 30 participants, 12 males and 18 females, aged between 18 and 54 years old, all of whom met the participant criteria.

[0051] Experimental Procedure: 30 participants met the eligibility criteria. Samples from each participant were placed into the small chamber of the plaque applicator, with a volume of approximately 0.020 mL to 0.025 mL. No substance was placed in the control well. The plaque applicator containing the test substance was then applied to the back or flexor side of the forearm of the participant using hypoallergenic adhesive tape. The applicator was gently pressed with the palm of the hand to ensure even application to the skin, and left for 24 hours. Skin reactions were observed at 30 minutes, 24 hours, and 48 hours after removing the plaque applicator, according to the criteria shown in Table 4. The observation results were recorded, and the grading criteria are shown in Table 4. The experimental results are shown in Table 5.

[0052] Table 4. Grading criteria for skin reaction in skin occlusion patch test.

[0053] degree of reaction Skin level Skin reaction - 0 negative reaction ± 1 Suspicious reaction, only slight erythema + 2 Weak positive reaction (erythema reaction); erythema, infiltration, edema, and papules may be present. ++ 3 Strong positive reaction (herpes reaction); erythema, infiltration, edema, papules, vesicles; the reaction may extend beyond the test area. +++ 4 Extremely strong positive reaction (confluent herpes simplex reaction); obvious erythema, severe infiltration, edema, confluent herpes simplex; reaction extends beyond the test area. .

[0054] Table 5. Results of human skin patch test in Example 1 and the control group of the present invention. .

[0055] As shown in Table 5, when the addition amount reaches 8% EffeMIX ® - HappyCalm does not irritate the skin.

[0056] 4.2 Human Clinical Testing 4.2.1 Experimental objective: To evaluate whether the cosmetic product has moisturizing effects by measuring the skin stratum corneum moisture content at multiple time points in the test (subject) area and the control (blank) area.

[0057] Reference method: QB / T 4256-2011 Guidelines for evaluating the moisturizing efficacy of cosmetics 4.2.2 Test subject: 2% EffeMIX®-HappyCalm aqueous solution obtained in Example 3 4.2.3 Testing Instruments Corneometer (Courage & Khazaka, Germany) - stratum corneum moisture content tester. 10–100 µL pipettes.

[0058] 4.2.4 Test Environment Environmental requirements: Temperature: 21.0℃ ± 1.0℃; Humidity: 50% ± 10%; 4.2.5 Subject Requirements 4.2.5.1 Informed consent has been signed, and participation in this test is voluntary. All participants received verbal and written informed consent in accordance with local regulations and procedures. The informed consent explained the nature and purpose of the study and the potential risks of participation, emphasizing the voluntary nature of participation and that participants could withdraw from the study at any time for any reason. All participants were given ample time to consider questions about the study before signing. All informed consent must be signed before the start of the study.

[0059] 4.2.5.2 Selection Criteria ① Open to both men and women, with preference given to women; ② Age 18-60 years old (at the start of the experiment); ③ Those who suffer from dry skin on the inner forearm; ④ The baseline value for the capacitive skin moisture meter in the forearm testing area is between 15 and 45 (Corneometer Unit, CU); ⑤ Subjects should not be sensitive to commonly used cosmetics; ⑥ The subject has not participated in any other clinical studies in the past three months; 4.2.5.3 Exclusion Criteria ① Use of antihistamines within the past week or immunosuppressants within the past month; ② No anti-inflammatory drugs were used on the test site within the past two months; ③ Insulin-dependent diabetic patients; ④ Patients with respiratory diseases who are currently receiving treatment; ⑤ Women who are breastfeeding or pregnant; ⑥ People with allergies, allergic dermatitis, or a history of skin diseases; ⑦ Individuals currently receiving dermatological treatment, or subjects who have taken hydroxy acids, whitening agents, or anti-aging drugs within the past month; ⑧ The test area had large areas of birthmarks, scratches, vitiligo, pigmented nevi, keloids, or other skin characteristics that would affect the test. In addition, the person in charge of the test determined that they were unsuitable to be subjects in this experiment.

[0060] 4.2.5.4 Restrictions ① During the experiment, hot water and spicy food are prohibited; ② During the test, frequent entry and exit from the constant temperature and humidity room is prohibited; ③ During the test, it is forbidden to cover the inside of the forearm or touch the test area. 4.2.5.5 Screening failure, subject dropout and replacement are handled systematically. Unenrolled subjects are those who signed informed consent forms but were not enrolled because they did not meet the inclusion / exclusion criteria.

[0061] A participant who leaves after randomization or assignment is considered a dropout. A participant who does not complete the study for any reason is also considered a dropout, and no replacement will be made in such cases.

[0062] Shedding criteria: Participant withdrawal consent: Participants may withdraw at any time for any reason (in accordance with the Helsinki Declaration); Adverse events / serious adverse events: Any event that the investigator believes would be detrimental to the subject if the trial were continued; Not following the plan; Subjects lost to follow-up; Other reasons: Reasons for other participants withdrawing.

[0063] In other cases, researchers believe that continued participation in the trial would be detrimental to the participants; This client has terminated their engagement.

[0064] The CRF form must be completed until the participant is deemed ineligible or drops out. All participants who terminate their trial early must have this recorded on the flowchart by the investigator or research team.

[0065] 4.2.6 Observation and Testing Sites Thirty-one volunteers were randomly selected from the inner forearm of their left and right hands as the experimental group and control group, respectively. This was a single-use trial.

[0066] 4.2.7 Observation and Test Items The instrument was tested on the subjects four times: before use, 2 hours after use, 4 hours after use, and 8 hours after use.

[0067] ① Stratum corneum moisture content: The average value was obtained by testing three times using a Corneometer.

[0068] ② Parameter explanation: The higher the value, the higher the water content of the stratum corneum of the skin.

[0069] ③ Result determination: After product use, the increase in stratum corneum moisture content in the test area is significantly higher than that in the blank area, indicating that the test sample has a moisturizing effect.

[0070] 4.2.8 Test Procedure ① On the first visit, explain the trial to the participants and obtain their informed consent.

[0071] ② Subjects should not use any products (cosmetics or topical medications) on the inner forearm for 2-3 days prior to the test, and should not allow the area to come into contact with water for 1-3 hours. Before the test, all subjects must clean the inner forearms of both hands uniformly by wiping them dry with a tissue. Measurement areas should be marked on the inner forearms of both hands, with each area at least 3cm x 3cm. Multiple areas can be marked on the same arm simultaneously, with at least 1cm between each area.

[0072] ③ The subjects participating in the trial were screened according to the trial requirements.

[0073] ④ After screening, qualified subjects should clean the test site and rest for 30 minutes in a temperature- and humidity-controlled room, refraining from drinking water or beverages. The forearm should be exposed and placed in the test position, remaining relaxed. After 30 minutes, instrument testing should be performed, using a Corneometer to measure the stratum corneum moisture content. The sample application area and blank control area should be randomly distributed across the marked areas on both arms to ensure statistically balanced distribution of all product and blank areas. The sample concentration is (2.0 ± 0.1) mg / cm². 2 Apply the sample in a single coat using the specified amount of latex. Wearing a latex finger cot, apply the sample evenly to the test area and record the actual amount of sample applied.

[0074] ⑤ After adjusting the instrument according to the instrument instruction manual, measure the product area and blank control area. First, measure the initial value of each test area (before sample use), and then measure the skin moisture content of the sample area and blank control area after the set time of 2h, 4h and 8h.

[0075] 4.2.9 Data Statistical Analysis Methods The GraphPad Prism software was used to perform descriptive statistics on each measurement value, including quantity, mean, standard deviation, minimum, median, and maximum.

[0076] Calculate the difference between the initial value of each test area and the measured value at other time points, and then use this difference to statistically analyze the differences between the product area and the blank control area at different time points.

[0077] If the test data are normally distributed, the t-test is used for statistical analysis; if the test data are not normally distributed, the rank-sum test is used for statistical analysis. The significance level for the statistical methods is p < 0.050.

[0078] 4.2.10 Test Results The results of the stratum corneum moisture content test are shown in Table 6, and the data comparison chart is shown in [the original text]. Figure 1 .

[0079] Table 6. Comparison of changes in stratum corneum moisture content between samples and blank samples .

[0080] 4.2.11 Conclusion According to QB / T 4256-2011, the Guidelines for Evaluating the Moisturizing Efficacy of Cosmetics, products containing 2% EffeMIX... ® - Detection was performed using HappyCalm aqueous solution.

[0081] In this trial population of 31 participants, after a single use of the test sample, the results of the test in the sample area and the blank control area showed that: 1. After using the test sample for 2 hours, compared with not using any product, the moisture content of the stratum corneum was significantly increased (P<0.001), indicating that the test sample has a 2-hour moisturizing effect.

[0082] 2. After using the test sample for 4 hours, compared with not using any product, the moisture content of the stratum corneum was significantly increased (P<0.001), indicating that the test sample has a 4-hour moisturizing effect.

[0083] 3. After using the test sample for 8 hours, compared with not using any product, the moisture content of the stratum corneum was significantly increased (P<0.001), indicating that the test sample has an 8-hour moisturizing effect.

[0084] Example 5. Soothing Efficacy Test 5.1 Human Clinical Testing 5.1.1 Experimental Objective 5.1.1.1 Using the pre- and post-treatment control principle and the parallel control principle, after 34 people used the sample continuously, the soothing efficacy of the sample was evaluated by statistically analyzing the initial value before sample use, the skin redness a* value after 2 weeks and 4 weeks of sample use.

[0085] 5.1.1.2 After 34 people used the sample continuously for 4 weeks, the soothing efficacy of the sample was evaluated based on the data from the consumer use test.

[0086] 5.1.2 Experimental Principle 5.1.2.1 Soothing Efficacy: Under the test conditions, the lower the a* value of skin redness and the lower the skin hemoglobin index value, the lower the degree of skin sensitivity and redness. After the sample was used, the a* value of skin redness and the skin hemoglobin index in the test area were significantly reduced, and there was a significant difference compared with the control group, indicating that the sample has a soothing effect.

[0087] 5.1.2.2 Four weeks after the subjects used the sample, they evaluated their satisfaction with the sample's efficacy using a questionnaire. The results of the questionnaire were judged and recorded.

[0088] Reference methods: (1) T / CAB0152—2022 "Test methods for seven effects of cosmetics: anti-wrinkle, firming, moisturizing, oil control, repair, nourishing and soothing". (2) Liu Weiyi, Zhou Lin, Zhao Hua. Evaluation of cosmetic efficacy - consumer use test [J]. Daily Chemical Industry, Vol.51, No.6, June 2021.

[0089] 5.2 Materials 5.2.1 Sample Information.

[0090] Table 7 Basic Information of Samples Sample Name quantity Specification Color and physical properties Production date / batch number Shelf life and expiration date Essence - Left cheek (base) 40 bottles 30g / bottle milky white essence December 1, 2023 1 year Serum - Right cheek (contains 1% EffeMIX®-HappyCalm) 40 bottles 30g / bottle milky white essence December 1, 2023 1 year .

[0091] For the serum - right cheek (containing 1% EffeMIX®-HappyCalm) formula, please refer to Example 2.

[0092] 5.2.2 Subjects: A total of 34 subjects, 0 males and 34 females, aged 21 to 60 years, with a mean age of 44 ± 11 years.

[0093] 5.2.3 Sample group: Use sample essence - right cheek (containing 1% EffeMIX®-HappyCalm).

[0094] 5.2.4 Control group: Sample essence - left cheek (matrix).

[0095] 5.3 Instruments Skin color measuring instrument (DCC1201, Delfin), Antera 3D imager (HC1023Q, Delfin), balance (accuracy 0.01g).

[0096] 5.4 Testing Environment The test environment temperature was 20.0℃~22.0℃ and the humidity was 40%~60%, which was dynamically monitored.

[0097] 5.5 Test Methods 5.5.1 On the first visit, explain the trial to the participants and obtain their informed consent.

[0098] 5.5.2 Subjects were screened according to the experimental requirements, and 34 subjects were selected to enter the experimental phase.

[0099] 5.5.3 On the day of the test, the subjects cleaned their faces and balanced in the test environment for 20 minutes. Then, the subjects' observed areas were photographed with an Antera 3D imager and their skin color was measured with a skin color meter.

[0100] 5.5.4 After the measurement is completed, the sample usage instructions are provided and the samples are distributed. The control group uses the essence - left face (base) once in the morning and once in the evening, 0.5g each time; the sample group uses the essence - right face (containing 1% EffeMIX®-HappyCalm) once in the morning and once in the evening, 0.5g each time. The sample weight is confirmed at the beginning and end of the test.

[0101] 5.5.5 Using an Antera 3D imager and skin color meter, photos and measurements were taken and questionnaires were completed at the designated follow-up time points.

[0102] 5.6 Results Analysis 5.6.1 Before-and-after comparison principle Descriptive statistics were performed on the measurements in each test area, including quantity, mean, and standard deviation.

[0103] Calculate the initial values ​​for each test area and the measured values ​​at other time points, and statistically analyze the differences between the measured values ​​and the initial values ​​at different times.

[0104] If the test data is normally distributed, the t-test method is used for statistical analysis; if the test data is not normally distributed, the rank-sum test method is used for statistical analysis.

[0105] All statistical methods employed two-tailed tests with a significance level of α = 0.05.

[0106] 5.6.2 Parallel Comparison Principle Descriptive statistics were performed on the measurements in each test area, including quantity, mean, and standard deviation.

[0107] Calculate the difference between the initial value of each test area and the measured value at other time points, and then use this difference to statistically analyze the differences between the sample group and the control group at different time points.

[0108] If the test data is normally distributed, the t-test method is used for statistical analysis; if the test data is not normally distributed, the rank-sum test method is used for statistical analysis.

[0109] All statistical methods employed two-tailed tests with a significance level of α = 0.05.

[0110] 5.7 Result Determination Positive results: Compared with before use, after use, the a* value of skin redness and the skin hemoglobin index of the test area were significantly reduced. Compared with the control group, the a* value of skin redness and the skin hemoglobin index of the test area of ​​the sample group were significantly different, indicating that the sample has a soothing effect.

[0111] Negative results: Compared with before use, there was no significant difference in the a* value of skin redness and the skin hemoglobin index of the test area after the sample was used, indicating that the sample does not have a soothing effect; or compared with the control group, there was no significant difference in the a* value of skin redness and the skin hemoglobin index of the test area after the sample group was used, indicating that the sample group does not have a soothing effect.

[0112] 5.8 Test Results 5.8.1 Sample Completion Status The enrollment was 36 participants, with 34 ultimately completing the test and 34 participating in the statistical analysis. See Appendix II: Participant Information and Appendix III: Participant Age Statistics for details.

[0113] 5.8.2 Product usage and tolerability feedback Each volunteer used the test sample as required within the specified time, and no adverse reactions were observed.

[0114] 5.8.3 Instrument test results and statistical analysis results 5.8.3.1 Results of a* value test for skin redness Table 8. Statistical analysis results of skin redness a* values ​​before and after use in the sample groups.

[0115] time N mean Statistical methods value Significance Downward adjustment rate Initial value (T0) 34 13.21±3.15 / / / / Use the sample for 2 weeks (T2). 34 10.65±2.91 test 0.000 ** 19.38% Use the sample for 4 weeks (T4). 34 8.28±3.07 test 0.000 ** 37.32% .

[0116] Note: Significance rating method: P ≥ 0.05 indicates no statistical difference ("ns"); P < 0.05 indicates a significant difference ("*"); P < 0.01 indicates a highly significant difference ("**").

[0117] Compared with before use, after 2 weeks and 4 weeks of sample use, the a* value of skin redness in the subjects decreased significantly, with downregulation rates of 19.38% and 37.32%, respectively.

[0118] Table 9. Statistical analysis results of parallel comparison between the sample group and the control group.

[0119] Time point Comparison of skin redness a* values Statistical methods value Significance 2 weeks Difference between sample group and control group test 0.000 ** 4 weeks Difference between sample group and control group rank-sum test 0.000 ** .

[0120] Note: Significance rating method: P ≥ 0.05 indicates no statistical difference ("ns"); P < 0.05 indicates a significant difference ("*"); P < 0.01 indicates a highly significant difference ("**").

[0121] Compared with the control group, the a* values ​​of skin redness in the subjects were significantly different after 2 weeks and 4 weeks of sample use.

[0122] 5.8.3.2 Results of Skin Hemoglobin Index Test Table 10 Statistical analysis results of skin hemoglobin index before and after use in the sample groups time N mean Statistical methods value Significance Downward adjustment rate Initial value (T0) 34 30.76±5.54 / / / / Use the sample for 2 weeks (T2). 34 28.89±4.71 test 0.000 ** 6.08% Use the sample for 4 weeks (T4). 34 27.38±4.82 test 0.000 ** 10.99% .

[0123] Note: Significance rating method: P ≥ 0.05 indicates no statistical difference ("ns"); P < 0.05 indicates a significant difference ("*"); P < 0.01 indicates a highly significant difference ("**").

[0124] Compared with before use, after 2 weeks and 4 weeks of sample use, the subjects' skin hemoglobin index decreased significantly, with downregulation rates of 6.08% and 10.99%, respectively.

[0125] Table 11 Statistical analysis results of parallel comparison between the sample group and the control group.

[0126] Time point Comparison of skin hemoglobin index Statistical methods value Significance 2 weeks Difference between sample group and control group test 0.037 * 4 weeks Difference between sample group and control group test 0.000 ** .

[0127] Note: Significance rating method: P ≥ 0.05 indicates no statistical difference ("ns"); P < 0.05 indicates a significant difference ("*"); P < 0.01 indicates a highly significant difference ("**").

[0128] Compared with the control group, the subjects showed significant differences in skin hemoglobin index after 2 and 4 weeks of sample use.

[0129] Furthermore, a traditional inclusion process was used to encapsulate kava pepper extract, milk thistle extract, and oat extract to form kava pepper extract supramolecular, milk thistle extract supramolecular, and oat extract supramolecular, respectively. These supramoleculars were then introduced into the aforementioned formulations. Comparison showed that the skin of subjects using this embodiment exhibited significant improvement, while the control group showed product / effect instability. We believe this may be because during the mixing and encapsulation of the three functional components, a multi-component synergistic complex system was formed based on weak intermolecular hydrogen bonds, van der Waals forces, and polar complementarity. This resulted in a synergistic amplification of anti-inflammatory, antioxidant, and barrier repair effects—a result of 1+1+1>3. Individual encapsulation, on the other hand, is merely a simple physical mixing without molecular-level synergy; it only adds up the effects without synergistic amplification. Furthermore, the mutual solubility of multiple polar / lipid-soluble components and the multi-component intercalation within the cyclodextrin cavity enhance the penetration of the stratum corneum. In contrast, single-component encapsulation releases each component independently, with a single penetration pathway and weak synergistic absorption. Furthermore, we found that the comparative formulations exhibited poor stability, such as: the product being more susceptible to oxidation due to precipitated silymarin, slight irritation due to precipitated kava, and the separation of oat polysaccharides. In summary, their overall antioxidant, anti-corrosion, acid and alkali resistance, high-temperature resistance, and irritation reduction effects were far inferior to the three single-component compound formulations in this embodiment.

[0130] 5.8.4 Statistics of Consumer Usage Test Results Table 12 Statistical results of safety evaluation after 4 weeks of sample use According to consumer testing, 100% of the participants experienced no irritation, redness, fever, itching, rash, acne, or other adverse reactions after using the sample for 4 weeks.

[0131] Table 13 Statistical results of mildness evaluation after 4 weeks of sample use. According to consumer use tests, 100% of the participants found the sample mild (non-irritating) after using it for 4 weeks.

[0132] Table 14 Statistical results of efficacy evaluation of the sample groups after 4 weeks of use. Note: The level of agreement is the sum of agreement and strong agreement.

[0133] According to consumer testing, after 4 weeks of use, 88% of participants reported improvements in facial redness; 85% reported reduced facial itching; 94% reported a calming and soothing effect on the face; 94% reported less facial burning; 94% reported less facial stinging; 94% reported increased skin hydration; 94% reported no tightness; 97% reported a refreshing feeling; and 91% reported improved skin stability.

[0134] Table 15 Statistical results of efficacy evaluation in the control group after 4 weeks of use. Questions / Options I strongly disagree Disagree generally Agree I strongly agree Approval After using this sample, facial redness was improved. 0% 0% 24% 38% 38% 76% After using this sample, facial itching was reduced. 0% 0% 21% 41% 38% 79% After using this sample, my face felt calm and soothed. 0% 0% 15% 47% 38% 85% This sample resulted in less burning sensation on the face after use. 0% 0% 18% 44% 38% 82% This sample caused less facial stinging after use. 0% 0% 21% 47% 32% 79% After using this sample, skin hydration improved. 0% 0% 15% 41% 44% 85% After using this sample, the face does not feel tight. 0% 0% 15% 41% 44% 85% After using this sample, the face felt refreshed. 0% 0% 18% 35% 47% 82% After using this sample, facial skin stability improved. 0% 0% 15% 53% 32% 85% .

[0135] Note: The level of agreement is the sum of agreement and strong agreement.

[0136] According to consumer testing, after using the control group sample for 4 weeks, 76% of the participants agreed that facial redness improved; 79% agreed that facial itching decreased; 85% agreed that their face felt calm and soothed; 82% agreed that their facial burning sensation was reduced; 79% agreed that their facial stinging sensation was reduced; 85% agreed that their skin hydration improved; 85% agreed that their face did not feel tight; 82% agreed that their face felt refreshed; and 85% agreed that their facial skin stability improved.

[0137] Table 16 Statistical results of user experience evaluation after 4 weeks of use in the sample group Questions / Options I strongly disagree Disagree generally Agree I strongly agree Approval After using this sample, my face felt "relaxed". 0% 0% 6% 35% 59% 94% After using this sample, the face felt "light". 0% 0% 6% 38% 56% 94% After using this sample, my face felt lighter and less burdened. 0% 0% 9% 41% 50% 91% After using this sample, my face felt "healed". 0% 0% 9% 32% 59% 91% After using this sample, the feeling of "fatigue" on the face was reduced. 0% 0% 12% 35% 53% 88% This sample can boost self-confidence and self-esteem after use. 0% 0% 9% 32% 59% 91% .

[0138] Note: The level of agreement is the sum of agreement and strong agreement.

[0139] According to consumer testing, after four weeks of use, 94% of the participants reported feeling a sense of relaxation in their face; 94% reported feeling a sense of lightness in their face; 91% reported feeling a sense of relief in their face; 91% reported feeling a sense of healing in their face; 88% reported a reduction in facial fatigue; and 91% reported improved self-confidence and self-esteem.

[0140] Table 17 Statistical results of user experience evaluation after 4 weeks of use in the control group Questions / Options I strongly disagree Disagree generally Agree I strongly agree Approval After using this sample, my face felt "relaxed". 0% 0% 15% 47% 38% 85% After using this sample, the face felt "light". 0% 0% 15% 44% 41% 85% After using this sample, my face felt lighter and less burdened. 0% 0% 18% 41% 41% 82% After using this sample, my face felt "healed". 0% 0% 15% 47% 38% 85% After using this sample, the feeling of "fatigue" on the face was reduced. 0% 0% 15% 56% 29% 85% This sample can boost self-confidence and self-esteem after use. 0% 0% 18% 44% 38% 82% .

[0141] Note: The level of agreement is the sum of agreement and strong agreement.

[0142] According to consumer testing, after using the control group sample for 4 weeks, 85% of the participants agreed that their faces felt "relaxed"; 85% agreed that their faces felt "light"; 82% agreed that their faces felt "lighter"; 85% agreed that their faces felt "healed"; 85% agreed that their facial "fatigue" was reduced; and 82% agreed that their self-confidence and self-esteem were boosted.

[0143] Table 18 Statistical Results on Whether Skin Condition Affects Mood Questions / Options It will have an impact It will not affect Does your skin condition affect your mood? 82% 18% .

[0144] Note: This may affect frequent, occasional, and rare occurrences.

[0145] According to consumer testing, 82% of respondents believed that skin condition affected their mood.

[0146] Table 19 Statistical results on whether negative emotions such as anxiety, sadness, and unease occur when skin problems occur. Questions / Options It will appear It will not appear Do you experience negative emotions such as anxiety, sadness, or unease when skin problems occur? 76% 24% .

[0147] Note: This may include frequent, occasional, and rare occurrences.

[0148] According to consumer testing, 76% of respondents felt negative emotions such as anxiety, sadness, and unease when skin problems occurred.

[0149] Table 20: Statistical results on whether soothing skincare products can regulate nerves and emotions and provide emotional value. Questions / Options There is hope It doesn't matter I don't want Do you want soothing skincare products to regulate your nerves and emotions, and provide emotional support? 85% 3% 12% .

[0150] Note: This may include both hopeful and general situations.

[0151] According to consumer testing, 85% of respondents would prefer soothing skincare products that can regulate nerves and mood, providing emotional value.

[0152] 5.9 Conclusion Human efficacy evaluation trials: After continuous use of the sample (serum - right cheek (containing 1% EffeMIX®-HappyCalm)) for 2 and 4 weeks, compared with before use, the subjects' skin redness a* value decreased significantly, with a reduction rate of 19.38% and 37.32%, respectively; the skin hemoglobin index decreased significantly, with a reduction rate of 6.08% and 10.99%, respectively. Compared with the control group, the subjects' skin redness a* value and skin hemoglobin index were significantly different, indicating that the sample (serum - right cheek (containing 1% EffeMIX®-HappyCalm)) has a soothing effect.

[0153] Consumer usage testing: According to consumer testing results, the sample (serum - right cheek (containing 1% EffeMIX®-HappyCalm)) has a soothing effect.

[0154] About the subjects:

[0155] 1) Healthy men / women aged 18-60; 2) Sensitive skin, i.e., a score of 18-42 on the West China Medical Center questionnaire; 3) Visible redness is present on the face; 4) The face is prone to discomfort such as itching, burning, and stinging; 5) Individuals without serious systemic diseases, immunodeficiency, or autoimmune diseases, and whose test sites have not undergone skin treatments, cosmetic procedures, or other tests that may affect the results; 6) Individuals without active allergic diseases; 7) Individuals without a highly sensitive constitution; 8) Those who have not used hormone medications or immunosuppressants in the past month; 9) Individuals who have not participated in other clinical trials at the test site in the past three months; 10) Has not undergone cosmetic procedures such as laser or chemical peels; 11) Able to cooperate well with the test subjects and maintain a regular lifestyle during the research period; 12) Able to read and understand all contents of the informed consent form and voluntarily sign the informed consent form; 13) Discontinue use of skin care products similar to the test sample during the trial period; 14) Will not participate in any other clinical trials at any other research centers during the trial period; 15) During the trial, it is agreed not to use any cosmetics, drugs, or health products that may affect the results.

[0156] Exclusion criteria 1) Use of antihistamines within the past week or immunosuppressants within the past month; 2) No anti-inflammatory medications have been used on the test site within the past two months; 3) Diabetic patients who rely on insulin; 4) Women who are breastfeeding or pregnant; 5) Patients with respiratory diseases who are currently receiving treatment; 6) People with allergies, allergic dermatitis, or a history of skin diseases; 7) Individuals currently receiving dermatological treatment, or subjects who have taken hydroxy acids, whitening agents, or anti-aging drugs within the past month; 8) The test area has large areas of birthmarks, scratches, vitiligo, pigmented nevi, keloids, or other skin characteristics that may affect the test.

[0157] Serial Number Group number Name gender age Has the experiment been completed? Whether to include 1 0001 QD female 36 yes yes 2 0002 MHJ female 55 yes yes 3 0003 WY female 36 yes yes 4 0004 WYN female 33 yes yes 5 0005 WHH female 46 yes yes 6 0006 XQ female 23 yes yes 7 0007 XYL female 59 yes yes 8 0008 DHY female 46 yes yes 9 0009 WXH female 51 yes yes 10 0010 ZXM female 55 yes yes 11 0011 LM female 53 yes yes 12 0012 - - - - - 13 0013 CHJ female 39 yes yes 14 0014 GXJ female 43 yes yes 15 0015 YH female 42 yes yes 16 0016 LN female 51 yes yes 17 0017 HL female 25 yes yes 18 0018 WWN female 46 yes yes 19 0019 - - - - - 20 0020 YF female 28 yes yes 21 0021 XY female 23 yes yes 22 0022 GS female 31 yes yes 23 0023 YCM female 50 yes yes 24 0024 ZJR female 36 yes yes 25 0025 ZH female 57 yes yes 26 0026 MSP female 51 yes yes 27 0027 WYL female 60 yes yes 28 0028 CGY female 59 yes yes 29 0029 WQ female 57 yes yes 30 0030 XHJ female 44 yes yes 31 0031 HM female 49 yes yes 32 0032 LHJ female 45 yes yes 33 0033 LBH female 53 yes yes 34 0034 LHY female 39 yes yes 35 0035 YY female 41 yes yes 36 0036 WKR female 21 yes yes .

[0158] Note: Subjects numbered 0012 and 0019 were not qualified during the screening.

Claims

1. A supramolecular composition with moisturizing and soothing effects, characterized in that: Composed of active ingredients and inclusion materials; The ratio of the active ingredient to the inclusion material is 3.0–7.0: 93.0–97.

0. The active ingredients are extracts of kava pepper, milk thistle, and oat extract; The mass ratio of the kava pepper extract, milk thistle extract, and oat extract is (0.5–1.0):(0.5–1.0):(2.0–5.0).

2. The supramolecular composition with moisturizing and soothing effects as described in claim 1, characterized in that: The inclusion material is hydroxypropyl cyclodextrin.

3. The supramolecular composition with moisturizing and soothing effects as described in claim 1, characterized in that: The degree of substitution of the inclusion material is 0.8 to 1.5, and the molecular weight is 1100 to 1300 Da.

4. The method for preparing a supramolecular composition with moisturizing and soothing effects as described in claim 1, characterized in that, It includes the following specific steps: S1. Supramolecular inclusion: Take kava pepper extract, milk thistle extract and oat extract respectively, mix them with the inclusion material according to the mass ratio, add ethanol, and heat and stir. S2. Spray drying: The inclusion solution of the active ingredient is spray dried to obtain a supramolecular inclusion dry powder with stable activity; S3. Sieving: The obtained supramolecular inclusion dry powder is sieved through an 80-100 mesh sieve to obtain a stable supramolecular composition.

5. The method for preparing a supramolecular composition with moisturizing and soothing effects as described in claim 1, characterized in that: The amount of ethanol added is:

6. The method for preparing a supramolecular composition with moisturizing and soothing effects as described in claim 1, characterized in that: The reaction conditions for S1 are:

7. The application of a supramolecular composition with moisturizing and soothing effects as described in any one of claims 1-3 in moisturizing and soothing products.

8. The application as described in claim 7, characterized in that: The supramolecular composition with moisturizing and soothing effects is added as an active ingredient at a concentration of 0.5–8.0 wt%.

9. A moisturizing and soothing product, characterized in that: The supramolecular composition with moisturizing and soothing effects described in any one of claims 1-3 is compounded with conventional cosmetic excipients to prepare aqueous solutions, emulsions, serums, creams, masks, gels, and jelly.

10. A moisturizing and soothing product as described in claim 9, characterized in that: The moisturizing and soothing products include water, lotion, serum, cream, mask, gel, shampoo, scalp care serum, conditioner, hair mask, shower gel and / or body scrub.

Images