A composition for treating atopic dermatitis and use thereof

Abstract

The present application belongs to the technical field of biological medicine, and particularly relates to a composition for treating atopic dermatitis and application thereof. The mass ratio of each component of the composition is: notoginseng extract: artemether: wujin glycoside: oleanolic acid = (2-4):(2-4):(1-2):(1-2). The composition has the effects of anti-inflammation and anti-itching, and can treat atopic dermatitis, eczema and other diseases. The active ingredients of the composition are all of plant origin, have good safety and the treatment effect on atopic dermatitis, and have a low dosage. The components can achieve a synergistic effect, and show excellent effects. The composition can be applied to functional skin care products (cream, emulsion, essence) and external drugs (ointment).

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a composition for treating atopic dermatitis and its application. Background Technology

[0002] Atopic dermatitis is an itchy, recurrent, chronic inflammatory skin disease, characterized by its chronicity, recurrence, and prevalence in children. Currently, the first-line treatment for atopic dermatitis is topical corticosteroids. However, topical corticosteroids increase the risk of skin atrophy, especially in skin folds, and may also affect growth and development, particularly in children. In the past two years, inhibitors targeting inflammatory targets such as calcineurin, IL4, IL13, and JAK have been approved for clinical use in atopic dermatitis, improving the treatment situation. However, these drugs are expensive, and some patients experience drug tolerance issues, making them unsuitable for long-term use in chronic diseases. Therefore, developing topical anti-inflammatory and antipruritic drugs with fewer side effects, high activity, and low cost is of great value for the treatment of atopic dermatitis.

[0003] Ginsenosides are a class of anti-inflammatory active substances widely distributed in plants of the genus *Panax* (such as ginseng, American ginseng, and *Panax notoginseng*). Rare saponins and diol-type saponins exhibit stronger immunomodulatory activity. Numerous studies have shown that ginsenosides have a good promoting effect on skin wound healing. Recent studies have indicated that compared to the main root, the saponins in the fibrous roots of *Panax notoginseng* contain more rare saponins, such as ginsenoside Rh1 and notoginsenoside R2, which may have better anti-inflammatory effects. Artemether is an important antimalarial drug, belonging to the artemisinin ether derivatives. It has lower polarity than artemisinin and better skin penetration. Studies have shown that artemether has a good therapeutic effect on atopic dermatitis, but it carries significant risks of neurotoxicity and hematologic toxicity. Oleanolic acid is a pentacyclic triterpenoid compound widely found in plant extracts. Oleanolic acid's anti-inflammatory and anti-cancer effects are widely recognized, but its hydrophobic nature results in low bioavailability, greatly limiting its potential for oral administration. However, it suggests potential for topical dermal application. Uloside, an arbutin derivative, is believed to have intestinal barrier repair functions and also possesses hypoglycemic, hypolipidemic, uric acid-lowering, and hepatoprotective effects, but its efficacy in treating atopic dermatitis has not yet been found. Therefore, using drug combinations to achieve reduced dosage and enhanced efficacy is an important strategy for the application of these drugs. Summary of the Invention

[0004] This invention proposes a composition consisting of Panax notoginseng extract, artemether, oleanolic acid, and quinoin. The four components synergistically enhance the anti-inflammatory effects of each, demonstrating potential for the treatment of atopic dermatitis. This composition exhibits both good safety and therapeutic efficacy for atopic dermatitis, requires a low dosage, and achieves a synergistic effect among the components, demonstrating excellent efficacy. A search revealed no reports of this combination in the treatment and research of atopic dermatitis.

[0005] In a first aspect, the present invention provides a composition for treating atopic dermatitis, wherein the weight ratio of each component is Panax notoginseng extract: artemether: oolong glycoside: oleanolic acid = (2~4): (2~4): (1~2): (1~2).

[0006] Preferably, the Panax notoginseng extract is a root extract of Panax notoginseng. This root extract contains 50%-80% total saponins, including 30%-50% ginsenoside Rb1, 5%-20% ginsenoside Rd, 5%-15% ginsenoside Rg1, 2%-10% notoginsenoside R2(s), and 0.5%-2% ginsenoside Rh1.

[0007] Preferably, the optimal weight ratio of each component is: Panax notoginseng extract: artemether: oolong glycoside: oleanolic acid = 2:2:1:1.

[0008] In a second aspect, the present invention provides a medicament for the prevention or treatment of atopic dermatitis, comprising the above-described composition for treating atopic dermatitis and a pharmaceutically acceptable carrier.

[0009] Preferably, the dosage form of the drug is any one of ointment, cream, external solution, tincture, lotion, powder or lyophilized powder.

[0010] Thirdly, the present invention provides the use of the above-described composition for treating atopic dermatitis in cosmetics.

[0011] Fourthly, the present invention provides a cosmetic comprising the above-described composition for treating atopic dermatitis and cosmetically acceptable excipients.

[0012] Preferably, the dosage form of the cosmetic is any one of emulsion, cream, gel or aqueous solution.

[0013] Preferably, the cosmetic product comprises the following components in parts by weight:

[0014] Cetearyl alcohol, 2 parts;

[0015] Squalane, 2 parts;

[0016] Polydimethylsiloxane, 1 part;

[0017] Glycerin, 6 parts;

[0018] Sodium hyaluronate, 0.1 parts;

[0019] Lecithin, 0.5 parts;

[0020] Soothing and anti-inflammatory agent, 1.2 parts;

[0021] 0.2 parts of p-hydroxyacetophenone

[0022] Water, 87 portions;

[0023] The soothing and anti-inflammatory agent is the composition for treating atopic dermatitis described above.

[0024] Compared with the prior art, the present invention has at least the following beneficial effects:

[0025] In a cellular epidermal inflammation model, at a final concentration of 10 μg / ml, none of the individual components—Panax notoginseng extract, linalool, or oleanolic acid—significantly inhibited the expression of the three biomarkers IL24, IL33, and CCL26. The inhibitory effect of artemether at 10 μg / ml was: IL24 reduced to 50% of the model group, IL33 reduced to 76% of the model group, and CCL26 reduced to 89% of the model group. The composition provided by this invention significantly inhibits the expression of atopic dermatitis biomarkers, and at the optimal ratio, IL24 is reduced to 39% of the model group, IL33 to 27% of the model group, and CCL26 to 64% of the model group, demonstrating significantly stronger inhibitory efficacy than the individual components at the same dosage. Therefore, the advantage of the composition of this invention lies in the excellent synergistic effect among its components, far superior to that of individual components.

[0026] Animal experiments have shown that the composition of this invention can significantly alleviate itching symptoms in mice, improve skin structure and clinical symptoms, and has an efficacy comparable to dexamethasone. Furthermore, at doses with similar efficacy, dexamethasone causes weight loss and spleen damage in mice, exhibiting significant immunotoxicity; while the composition effectively improves mouse weight without affecting spleen weight, demonstrating better safety.

[0027] The composition of this invention has anti-inflammatory and antipruritic effects, and can treat diseases such as atopic dermatitis. All active ingredients in this composition are plant-derived, possessing both good safety and therapeutic efficacy for atopic dermatitis. Furthermore, the dosage is low, and the components exhibit synergistic effects, demonstrating excellent efficacy. It can be applied to functional skincare products (creams, lotions, serums) and topical medications (lotions, ointments). Attached Figure Description

[0028] Figure 1The effects of different ratios of the composition and a single component on the relative expression level of the IL24 gene in the IL4 / IL13-induced epidermal inflammation model of the present invention;

[0029] Figure 2 The effects of different ratios of the composition and single component on the relative expression level of the IL33 gene in the IL4 / IL13-induced epidermal inflammation model of the present invention;

[0030] Figure 3 The effects of different ratios of the composition and a single component on the relative expression level of the CCL26 gene in the IL4 / IL13-induced epidermal inflammation model of the present invention;

[0031] Figure 4 The effect of the composition of this invention combined with dexamethasone on improving the clinical scores of mice with atopic dermatitis (n=6).

[0032] Figure 5 The effect of the composition of this invention combined with dexamethasone on improving the body weight of mice with atopic dermatitis (n=6).

[0033] Figure 6 The effect of the composition of this invention and dexamethasone on the spleen coefficient in atopic dermatitis mice (n=6) was investigated.

[0034] Figure 7 The effect of the composition of this invention combined with dexamethasone on the atopic dermatitis symptoms in mice (n=6);

[0035] Figure 8 The effect of the composition of this invention combined with dexamethasone on the skin structure of mice with atopic dermatitis (n=6). Detailed Implementation

[0036] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention is determined by the claims.

[0037] Unless otherwise specified, the raw materials and materials used in the embodiments of the present invention were purchased through general commercial channels.

[0038] The source information of the raw materials, instruments, and equipment involved in the following embodiments or application examples is as follows:

[0039] Experimental reagents:

[0040] Artemether, B20493, Shanghai Yuanye Biotechnology Co., Ltd.;

[0041] Wujinan, WKQ-0000889, Sichuan Weikeqi Biotechnology Co., Ltd.;

[0042] Oleanolic acid, A10055, Shanghai Yuanye Biotechnology Co., Ltd.;

[0043] DMEM high-glucose medium, Gibco, Thermo Fisher Scientific Inc. (USA);

[0044] Fetal bovine serum, Gibco, Thermo Fisher Scientific Inc. (USA);

[0045] Cytokines IL4 (GP20499) and IL13 (GP20560), GlpBio Technology (USA);

[0046] Dimethyl sulfoxide (DMSO), 14200201, Xilong Scientific Co., Ltd.;

[0047] Cetearyl alcohol (CAS: 67762-27-0), S26921, Shanghai Yuanye Biotechnology Co., Ltd.;

[0048] Squalane (CAS: 111-01-3), S22248, Shanghai Yuanye Biotechnology Co., Ltd.;

[0049] Polydimethylsiloxane (CAS: 70131-67-8), T22990, Shanghai Yuanye Biotechnology Co., Ltd.;

[0050] Lecithin (CAS: 8002-43-5), T90784, Shanghai Yuanye Biotechnology Co., Ltd.;

[0051] p-Hydroxyethyl ketone (CAS: 99-93-4), A10384, Shanghai Yuanye Biotechnology Co., Ltd.

[0052] Experimental apparatus:

[0053] CO2 incubator (Series 2 Water Jacketed, Thermo Fisher, USA);

[0054] Microcentrifuge (Fresco 21, Thermo Fisher, USA);

[0055] qPCR instrument (Applied Biosystems QuantStudio 3, Thermo Fisher, USA).

[0056] In this invention, the Panax notoginseng root extract is prepared in-house, and the preparation method is as follows:

[0057] The roots of Panax notoginseng were dried, pulverized, and extracted by heating and reflux with 85% ethanol at a material-to-liquid ratio of 1:10 (g / ml). The heating temperature was 60-80 degrees Celsius, and the extraction was repeated twice. The ethanol was removed by rotary evaporation under reduced pressure at 50-60 degrees Celsius and the solution was concentrated to obtain the concentrated liquid.

[0058] The concentrated extract was adsorbed using AB-8 macroporous resin, and eluted fractionally with water (30% and 50%) for 2-7 BV. The eluent of 60% ethanol (5-8 BV) was collected and freeze-dried to obtain the Panax notoginseng root extract. By weight, the total saponin content of the Panax notoginseng root extract was 50%-80%, including ginsenoside Rb1 30%-50%, ginsenoside Rd 5%-20%, ginsenoside Rg1 5%-15%; notoginsenoside R2(s) 2%-10%; and ginsenoside Rh1 0.5%-2%.

[0059] The Panax notoginseng root extract used in the embodiments of the present invention has a saponin content of 60.4% by weight; it mainly contains ginsenoside Rb1 38.2%, ginsenoside Rd 6.2%, ginsenoside Rg1 9.1%, Panax notoginseng saponin R2 5.1%, and ginsenoside Rh1 0.72%.

[0060] Statistical analysis

[0061] All data in this invention comprise at least three independent replicates, and are expressed as mean. All data were plotted and statistically analyzed using GraphPad Prism software. Statistical analysis was performed using one-way / multi-way ANOVA or independent samples t-tests. A p-value ≤ 0.05 was considered statistically significant.

[0062] <Example 1>

[0063] Take 2.5 mg of Panax notoginseng root extract, 2.5 mg of artemether, 2.5 mg of quinoin and 2.5 mg of oleanolic acid, mix them and dissolve them in 1 ml of DMSO to complete the preparation of the mother liquor of composition 1.

[0064] The mother liquor was diluted 1000 times with culture medium to obtain the working solution of composition 1 for testing. The final concentration of composition 1 contained in the working solution was 10 μg / ml, and the mass ratio of each component was 1:1:1:1; that is, the final concentration was 2.5 μg / ml of Panax notoginseng root extract, 2.5 μg / ml of artemether, 2.5 μg / ml of quinoin, and 2.5 μg / ml of oleanolic acid.

[0065] In an in vivo epidermal inflammation model, composition 1 significantly inhibited the expression of inflammatory genes IL24, IL33, and CCL26. Compared with the model group, IL24 was downregulated to 61% (see...). Figure 1IL33 was lowered to 24% (see) Figure 2 CCL26 was lowered to 72% (see) Figure 3 All three genes were significantly downregulated compared to Example 13.

[0066] <Example 2>

[0067] Prepare the mother liquor and working solution of Composition 2. The working solution of Composition 2 is used for testing, and its final concentration of Composition 2 is 10 μg / ml. The steps are the same as in Example 1, except that the mass ratio of each component is 2:1:1:1; that is, the final concentration of each component is 4 μg / ml of Panax notoginseng root extract, 2 μg / ml of artemether, 2 μg / ml of quinoin, and 2 μg / ml of oleanolic acid.

[0068] In an in vivo epidermal inflammation model, composition 2 significantly inhibited the expression of inflammatory genes IL24, IL33, and CCL26. Compared with the model group, IL24 was downregulated to 63% (see...). Figure 1 IL33 was lowered to 17% (see) Figure 2 CCL26 was lowered to 73% (see) Figure 3 All three genes were significantly downregulated compared to Example 13.

[0069] <Example 3>

[0070] Prepare the mother liquor and working solution of Composition 3. The working solution of Composition 3 is used for testing, and its final concentration of the composition is 10 μg / ml. The steps are the same as in Example 1, except that the mass ratio of each component is 1:2:1:1; that is, the final concentration is 2 μg / ml of Panax notoginseng root extract, 4 μg / ml of artemether, 2 μg / ml of quinoin, and 2 μg / ml of oleanolic acid.

[0071] In an in vivo epidermal inflammation model, the working solution of composition 3 significantly inhibited the expression of inflammatory genes IL24, IL33, and CCL26. Compared with the model group, IL24 was downregulated to 56% (see...). Figure 1 IL33 was lowered to 45% (see) Figure 2 CCL26 was lowered to 59% (see) Figure 3 All three genes were significantly downregulated compared to Example 13.

[0072] <Example 4>

[0073] The mother liquor and working solution of Composition 4 were prepared. The working solution of Composition 4 was used for testing, and its final concentration of the composition was 10 μg / ml. The steps were the same as in Example 1, except that the mass ratio of each component was 1:1:2:1; that is, the final concentration was 2 μg / ml of Panax notoginseng root extract, 2 μg / ml of artemether, 4 μg / ml of quinoin, and 2 μg / ml of oleanolic acid.

[0074] In an in vivo epidermal inflammation model, the working solution of Composition 4 significantly inhibited the expression of inflammatory genes IL24 and IL33, but not CCL26 (see...). Figure 3 Compared to the model group, IL24 was reduced to 76% (see...). Figure 1 IL33 was lowered to 75% (see) Figure 2 The two genes mentioned above showed no significant difference compared to Example 13.

[0075] <Example 5>

[0076] Prepare the mother liquor and working solution of Composition 5. The working solution of Composition 5 is used for testing, and its final concentration of the composition is 10 μg / ml. The steps are the same as in Example 1, except that the mass ratio of each component is 1:1:1:2; that is, the final concentration is 2 μg / ml of Panax notoginseng root extract, 2 μg / ml of artemether, 2 μg / ml of quinoin, and 4 μg / ml of oleanolic acid.

[0077] In an in vivo epidermal inflammation model, the working solution of composition 5 significantly inhibited the expression of the inflammatory gene IL33 but not IL24 (see...). Figure 1 ) and CCL26 (see Figure 3 Compared to the model group, IL33 was reduced to 9%, and IL33 was significantly reduced compared to Example 13 (see Example 13). Figure 2 ).

[0078] <Example 6>

[0079] The mother liquor and working solution of Composition 6 were prepared. The working solution of Composition 6 was used for testing, and its final concentration of the composition was 10 μg / ml. The steps were the same as in Example 1, except that the mass ratio of each component was 2:2:1:1; that is, the final concentration was 3.33 μg / ml of Panax notoginseng root extract, 3.33 μg / ml of artemether, 1.67 μg / ml of quinoa extract, and 1.67 μg / ml of oleanolic acid.

[0080] In an in vivo epidermal inflammation model, the working solution of Composition 6 significantly inhibited the expression of inflammatory genes IL24, IL33, and CCL26. Compared with the model group, IL24 was downregulated to 39% (see...). Figure 1 IL33 was lowered to 27% (see) Figure 2 CCL26 was lowered to 64% (see) Figure 3 All three genes were significantly downregulated compared to Example 13.

[0081] <Example 7>

[0082] The mother liquor and working solution of Composition 7 were prepared. The working solution of Composition 7 was used for testing, and its final concentration of the composition was 10 μg / ml. The steps were the same as in Example 1, except that the mass ratio of each component was 3:1:1:1; that is, the final concentration was 5 μg / ml of Panax notoginseng root extract, 1.67 μg / ml of artemether, 1.67 μg / ml of quinoa extract, and 1.67 μg / ml of oleanolic acid.

[0083] In an in vivo epidermal inflammation model, the working solution of Composition 7 significantly inhibited the expression of the inflammatory gene IL33 but not IL24 (see...). Figure 1 ) and CCL26 (see Figure 3 Compared to the model group, IL33 was reduced to 21%, and significantly reduced compared to Example 13 (see Example 13). Figure 2 ).

[0084] <Example 8>

[0085] The mother liquor and working solution of Composition 8 were prepared. The working solution of Composition 8 was used for testing, and its final concentration of the composition was 10 μg / ml. The steps were the same as in Example 1, except that the mass ratio of each component was 1:3:1:1; that is, the final concentration was 1.67 μg / ml of Panax notoginseng root extract, 5 μg / ml of artemether, 1.67 μg / ml of quinoa extract, and 1.67 μg / ml of oleanolic acid.

[0086] In an in vivo epidermal inflammation model, the working solution of Composition 8 significantly inhibited the expression of inflammatory genes IL24 and CCL26, but not IL33 (see...). Figure 2 Compared to the model group, IL24 was reduced to 46% (see...). Figure 1 CCL26 was lowered to 58% (see) Figure 3 The two genes mentioned above were significantly downregulated compared to Example 13.

[0087] <Example 9>

[0088] The mother liquor and working solution of Composition 9 were prepared. The working solution of Composition 9 was used for testing, and its final concentration of the composition was 10 μg / ml. The steps were the same as in Example 1, except that the mass ratio of each component was 3:3:1:1; that is, the final concentration was 3.25 μg / ml of Panax notoginseng root extract, 3.25 μg / ml of artemether, 1.08 μg / ml of quinoa extract, and 1.08 μg / ml of oleanolic acid.

[0089] In an in vivo epidermal inflammation model, the working solution of Composition 9 significantly inhibited the expression of inflammatory genes IL24, IL33, and CCL26. Compared with the model group, IL24 was downregulated to 35% (see...). Figure 1 IL33 was lowered to 47% (see) Figure 2 CCL26 was lowered to 65% (see) Figure 3 All three genes were significantly downregulated compared to Example 13.

[0090] <Example 10>

[0091] Prepare the mother liquor and working solution of Composition 10. The working solution of Composition 10 is used for testing, and its final concentration of composition is 10 μg / ml. The steps are the same as in Example 1, except that the mass ratio of each component is 4:4:1:1; that is, the final concentration is 4 μg / ml of Panax notoginseng root extract, 4 μg / ml of artemether, 1 μg / ml of quinoin, and 1 μg / ml of oleanolic acid.

[0092] In an in vivo epidermal inflammation model, the working solution of composition 10 significantly inhibited the expression of inflammatory genes IL24, IL33, and CCL26. Compared with the model group, IL24 was downregulated to 60% (see...). Figure 1 IL33 was lowered to 46% (see) Figure 2 CCL26 was lowered to 72% (see) Figure 3 All three genes were significantly downregulated compared to Example 13.

[0093] <Example 11>

[0094] The mother liquor and working solution of Composition 11 were prepared. The working solution of Composition 11 was used for testing, and its final concentration of the composition was 30 μg / ml. The steps were the same as in Example 1, except that the mass ratio of each component was 5:5:1:1; that is, the final concentration was 4.17 μg / ml of Panax notoginseng root extract, 4.17 μg / ml of artemether, 0.83 μg / ml of quinoa extract, and 0.83 μg / ml of oleanolic acid.

[0095] In an in vivo epidermal inflammation model, the working solution of composition 11 significantly inhibited the expression of inflammatory genes IL24 and IL33, but not CCL26 (see...). Figure 3 Compared to the model group, IL24 was reduced to 54% (see...). Figure 1 IL33 was lowered to 63% (see) Figure 2 Of the two genes mentioned above, IL24 was significantly downregulated compared to Example 13, while the expression level of IL33 was not significantly different from that in Example 13.

[0096] <Example 12>

[0097] 100 mg of Panax notoginseng root extract was dissolved in 1 ml of DMSO to prepare the mother liquor of Panax notoginseng root extract. The mother liquor was diluted 1000, 2000 and 10000 times with culture medium to obtain working solutions of Panax notoginseng root extract for testing. The final concentrations of Panax notoginseng root extract contained in these solutions were 10 μg / ml, 50 μg / ml and 100 μg / ml, respectively.

[0098] In an in vivo epidermal inflammation model, 10 μg / ml Panax notoginseng root extract did not significantly inhibit the expression of inflammatory genes, while 50 μg / ml significantly inhibited the expression of the inflammatory gene IL33, downregulating IL33 to 37% of the model group. 100 μg / ml Panax notoginseng root extract significantly inhibited the expression of the inflammatory genes IL24 and IL33, downregulating IL24 to 41% of the model group and IL33 to 17% of the model group (see...). Figure 4 ).

[0099] <Example 13>

[0100] Dissolve 10 mg of artemether in 1 ml of DMSO to prepare the artemether mother liquor. Dilute the mother liquor 1000 times with culture medium to obtain the artemether working solution for testing. The final concentration of artemether contained in the working solution is 10 μg / ml.

[0101] In an in vivo epidermal inflammation model, 10 μg / ml artemether significantly inhibited the expression of inflammatory genes IL24, IL33, and CCL26, with IL24 downregulated to 50% of the model group (see [link to relevant data]). Figure 1 ), IL33 was reduced to 76% of the model group (see Figure 2 CCL26 was reduced to 89% of the model group (see) Figure 3 ).

[0102] <Example 14>

[0103] 450 mg of quinoin was dissolved in 1 ml of DMSO to prepare the quinoin mother solution. The mother solution was diluted 1000 times with culture medium to obtain quinoin working solution 1 for testing, with a final concentration of quinoin of 450 μg / ml. The mother solution was then diluted 45000 times with culture medium to obtain quinoin working solution 2 for testing, with a final concentration of quinoin of 10 μg / ml.

[0104] In an in vivo epidermal inflammation model, 10 μg / ml ginseng did not significantly inhibit the expression of inflammatory genes IL24, IL33, and CCL26, while 450 μg / ml ginseng significantly inhibited the expression of inflammatory genes IL33 and CCL26, but not IL24. IL33 was downregulated to 40% in the model group (see...). Figure 2 CCL26 was reduced to 79% of the model group (see) Figure 3 ).

[0105] <Example 15>

[0106] Dissolve 10 mg of oleanolic acid in 1 ml of DMSO to prepare the oleanolic acid mother liquor. Dilute the mother liquor 1000 times with culture medium to obtain the oleanolic acid working solution for testing. The final concentration of oleanolic acid in the working solution is 10 μg / ml.

[0107] In an in vivo epidermal inflammation model, 10 μg / ml oleanolic acid did not significantly inhibit the expression of inflammatory genes IL24, IL33, and CCL26 (see...). Figure 1-3 ).

[0108] <Example 16>

[0109] The mother liquor and working solution of Composition 16 were prepared. The working solution of Composition 16 was used for testing, and its final concentration of the composition was 10 μg / ml. The steps were the same as in Example 6, except that the mass ratio of each component was Panax notoginseng root extract: artemether: oleanolic acid = 2:2:1; that is, the final concentration was 4 μg / ml of Panax notoginseng root extract, 4 μg / ml of artemether, and 2 μg / ml of oleanolic acid.

[0110] In an in vivo epidermal inflammation model, the working solution of composition 16 significantly inhibited the inflammatory gene IL24 but not IL33, CCL26 (see...). Figure 2-3 Compared to the model group, IL24 was reduced to 29% (see...). Figure 1 (), significantly lower than in Example 13.

[0111] <Test Example 1>

[0112] The process of establishing the in vivo epidermal inflammation model is as follows:

[0113] Human keratinocyte cell line HaCaT was purchased from ATCC. Cells were cultured in DMEM high-glucose complete medium containing 10% FBS and 1% penicillin-antibiotics at 37°C and 5% CO2. Experiments were conducted using cells in the logarithmic growth phase, and drug stimulation was performed when cell confluence reached approximately 70%.

[0114] HaCaT cells were co-incubated with 50 ng / ml IL4 and IL13 for 24 h to serve as an epidermal inflammation model. In the drug treatment group, a combination of Panax notoginseng root extract, linalool, artemether, oleanolic acid, and other ingredients was administered simultaneously with IL4 / IL13. After 24 hours of incubation, qPCR was performed to detect the inflammatory genes IL24, IL33, and CCL26. Results are shown below. Figures 1-5 And Tables 1-3.

[0115] The above Figures 1-3 In the diagram, # represents a significant difference between Example 12, Example 13, or Example 14 and the model group. # represents p≤0.05; ## represents p≤0.01; ### represents p≤0.001. * represents a significant difference between Examples 1-11 and Example 13. * represents p≤0.05; ** represents p≤0.01; *** represents p≤0.001.

[0116] Table 1. Regulatory effects of different ratios of the combined composition and single component on the expression of epidermal inflammation genes.

[0117]

[0118] <Test Example 2>

[0119] The experimental animals were SPF-grade male Balb / c mice, 7-8 weeks old, weighing 20-25g, sourced from Beijing Vital River Laboratory Animal Technology Co., Ltd., animal qualification certificate number No. 110011241110592062. Animals were housed in individually ventilated cages, with no more than 5 animals per cage. The ambient temperature was maintained at 20-26ºC, humidity at 35-75%, with 12 hours of light and 12 hours of darkness, and free access to water and food. This experimental protocol and any modifications were approved by the Laboratory Animal Welfare and Ethics Committee of Hefei Zhongke Puruisheng Biomedical Technology Co., Ltd. (IACUC-20241101).

[0120] This experiment included a solvent group, a model group, a positive drug group, a low-dose composition group, and a high-dose composition group, with 6 mice randomly assigned to each group. Acetone and olive oil were mixed at a volume ratio of 4:1 as a blank solvent. The composition from Example 6 was used as the test drug, with the mass ratio of Panax notoginseng root extract: artemether: oleanolic acid: linalool = 2:2:1:1. Two doses, 0.3% and 0.6% (W / V, g / ml), were used as the low-dose and high-dose groups, respectively. Dexamethasone was used as the positive drug at a dose of 0.04% (W / V, g / ml) as the positive drug group. A mouse atopic dermatitis model induced by MC903 was established, with the blank solvent administered as the model group. Non-model mice were given the blank solvent as the solvent group. The mouse MC903 atopic dermatitis model was as follows:

[0121] Mice underwent hair removal on their backs, and the sensitizing substance MC903, or MC903 combined with the drug (Example 6), was applied daily to the hair removal area. Mice weight was measured daily, and scratching behavior and skin condition at the test sites were observed, with clinical scores recorded. After 14 days, the backs of the mice were photographed, and the mice were sacrificed; the skin from the test sites was collected. Mouse skin was stained with hematoxylin and eosin (HE) to observe the morphology of the epidermis and dermis. Results are shown below. Figures 6-8 and Tables 4-6. Among them, Figure 7 In the table, A represents the total number of scratches by the mouse within a fixed time period (30 minutes); B represents the total duration (in seconds) of scratching behavior by the mouse within a fixed time period (30 minutes). Figure 8 In the image, A is a HE-stained image of mouse skin tissue (20X); B is a statistical representation of the thickness (micrometers) of the epidermal layer in mouse skin.

[0122] Table 2. Effects of the combination of the ingredients and dexamethasone on the clinical scores of mice with atopic dermatitis over time.

[0123]

[0124] Table 3. Effects of the combination of the ingredients and dexamethasone on the body weight of mice with atopic dermatitis over time.

[0125]

[0126] Table 4. Effects of the composition and dexamethasone on spleen, epidermis, and pruritus symptoms in mice with atopic dermatitis.

[0127]

[0128] The results showed that on day 14 of treatment, the 0.6% dose of the composition significantly reduced the clinical score of atopic dermatitis in mice, with results similar to those in the dexamethasone group. Figure 4 ).

[0129] On day 14 of treatment, the body weight of mice in the 0.6% dose group was significantly higher than that of mice in the model group and the dexamethasone group, indicating that this dose of the composition did not produce significant toxic side effects in mice and was beneficial to the recovery of mice with atopic dermatitis. Figure 5 ).

[0130] On day 14 of treatment, the spleen index of mice in the 0.6% composition group was not significantly different from that in the solvent group and the model group, while the spleen index of mice in the dexamethasone group decreased significantly, indicating that this dose of composition did not produce immunotoxicity similar to that of dexamethasone. Figure 6 ).

[0131] On day 14 of treatment, the number of scratches and the duration of scratching were significantly less in the 0.3% and 0.6% combination groups and the dexamethasone group than in the model group, suggesting that all three drugs could significantly alleviate the itching symptoms in mice. Figure 7 ).

[0132] On day 14 of treatment, the epidermal thickness of mice in the 0.3% and 0.6% combination groups and the dexamethasone group was significantly smaller than that in the model group, and the epidermal structure was more compact, suggesting that all three drugs can significantly improve the skin structure of mice and alleviate epidermal thickening caused by atopic dermatitis. Figure 8 ).

[0133] <Application Example 1>

[0134] This application example provides a moisturizing cream with soothing and antipruritic effects. The formula of the moisturizing cream is shown in Table 5 below:

[0135] Table 5. Moisturizing Cream Formula

[0136]

[0137] Its preparation method is as follows:

[0138] (1) Add the A phase raw material to the oil phase pot, stir and heat to 85°C;

[0139] (2) Add phase B and phase E raw materials to the aqueous phase pot, mix evenly, and then heat to 85°C with stirring.

[0140] (3) The materials in the water phase pot and oil phase pot are drawn into the emulsification pot under negative pressure, homogenized for 10 minutes, cooled to 75°C, D phase raw material is added, stirring is continued, the temperature is cooled to 40°C, C phase raw material is added, and after mixing evenly, the product is obtained.

[0141] The soothing and anti-inflammatory agents in Table 5 above were prepared by directly weighing Panax notoginseng extract, artemether, quinoin and oleanolic acid according to the proportions in Example 6.

[0142] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A composition for treating atopic dermatitis, characterized in that, The mass ratio of each component is Panax notoginseng extract: artemether: linalool: oleanolic acid = 2:2:1:

1. The Panax notoginseng extract is derived from the fibrous roots of Panax notoginseng. The total saponin content in the Panax notoginseng fibrous root extract is 50%-80%, including ginsenoside Rb1 30%-50%, ginsenoside Rd 5%-20%, ginsenoside Rg1 5%-15%; Panax notoginseng saponin R2(s) 2%-10%; and ginsenoside Rh1 0.5%-2%.

2. A drug for the prevention or treatment of atopic dermatitis, characterized in that, It consists of the composition for treating atopic dermatitis as described in claim 1 and a pharmaceutically acceptable carrier.

3. The use of the composition for treating atopic dermatitis according to claim 1 in the preparation of a medicament for the prevention or treatment of atopic dermatitis.

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