Composition for treating rosacea as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of acne rosacea treatment, and discloses a preparation method and application of a composition for treating acne rosacea, the composition for treating acne rosacea contains a moutan bark extract and a coptis chinensis extract, and also contains a lucid ganoderma extract, a cinnamon extract, paeoniflorin and syringic acid. The inflammatory response of rosacea is closely related to the expression of two core inflammatory factors, namely TNF-alpha and TLR4, and the invention consciously aims at the TLR4-TNF-alpha inflammatory axis multi-target design, inhibits the expression of TLR4 and TNF-alpha, and blocks the'start-amplification 'chain of inflammation, thereby inhibiting the recurrence of inflammation. In addition, the composition for treating rosacea provided by the invention can also improve capillary dysfunction, effectively inhibit microbial growth, and prevent and treat rosacea from multiple dimensions.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of a rose acne treatment composition, and more particularly to a rose acne treatment composition and a preparation method and application thereof. BACKGROUND

[0002] Rose acne, also known as rhinophyma, is a common chronic inflammatory skin disease with an incidence rate of about 22%, and is more common in young women. The pathogenesis of rose acne is mainly due to local inflammation caused by ultraviolet damage, environmental factors, genetic factors, microorganisms and oxidative stress, resulting in the production of LL37 and other antibacterial peptides and inflammatory factors, and the dysfunction of local capillary vasomotor nerves, leading to the appearance of persistent redness, capillary dilation, papules, pustules and other symptoms in the central face, which often have disfiguring characteristics and seriously affect the appearance of patients.

[0003] The prior art uses cortex moutan extract and coptis extract to decoct with radix rehmanniae, safflower, psoralea and other medicinal materials to obtain a smearing product or oral decoction, which can relieve the redness, papules, pustules and other problems caused by rose acne to a certain extent, but has the following problems, resulting in limited treatment effect on rose acne: (1) Insufficient inflammation suppression: In the prior art, the anti-inflammatory components of cortex moutan extract and the active components of coptis extract can only temporarily relieve the inflammatory symptoms such as redness and papules of rose acne, but cannot effectively regulate the key factors that trigger inflammatory reactions. Once the external environment is stimulated or the body state fluctuates, inflammation will be activated again, resulting in the inability of existing products to fundamentally curb the repeated occurrence of inflammation.

[0004] (2) Unable to improve capillary dysfunction: The persistent redness and abnormal capillary dilation caused by rose acne are mainly due to the dysfunction of capillary vasomotor nerves (such as neurotransmitter disorder and enhanced vascular reactivity), which stimulates the local tissue to produce vascular endothelial growth factor (VEGF) to promote the "germination" of existing capillaries to form new blood vessels, resulting in abnormal blood vessels. Abnormal angiogenesis further disrupts the function of capillary vasomotor nerves, aggravating symptoms such as persistent redness and abnormal capillary dilation. Existing medicinal materials (such as radix rehmanniae and psoralea, which are slightly cool blood, and safflower, which is slightly blood-activating) indirectly relieve redness by regulating blood circulation, but cannot curb abnormal angiogenesis.

[0005] (3) Limited inhibition of excessive microbial proliferation: Excessive proliferation of Demodex folliculorum can activate TLR4 to trigger inflammation. The existing technology has no clear effect on the targeted killing or inhibition of Demodex, and lacks intervention on other related microorganisms (such as Propionibacterium acnes). Under the continuous stimulation of microorganisms, papules and pustules are prone to recur. SUMMARY

[0006] The present application provides a composition for treating rosacea, which has better effects on inhibiting inflammation, or improving capillary dysfunction, or inhibiting excessive microbial proliferation than prior art.

[0007] Another object of the present application is to provide a preparation method of the composition for treating rosacea.

[0008] Another object of the present application is to provide the use of the composition for treating rosacea in the preparation of a product for treating rosacea.

[0009] Since the inflammatory response of rosacea is closely related to the expression of two core inflammatory factors TNF-α and TLR4, the core inflammatory factor TNF-α is a tumor necrosis factor that amplifies the inflammatory signal and aggravates the inflammatory response, and the core inflammatory factor TLR4 first recognizes lipopolysaccharide released by microbial activity and then initiates a cell signaling pathway to promote the release of pro-inflammatory factors, leading to repeated inflammation. Therefore, the present application is designed to target multiple targets of the TLR4-TNF-α inflammatory axis, inhibit the expression of TLR4 and TNF-α, and block the "start-amplification" chain of inflammation, so as to inhibit the repeated occurrence of inflammation.

[0010] To solve the above technical problems, the technical scheme provided by the present application is: A composition for treating rosacea, containing cortex moutan extract and coptis extract, and also containing ganoderma extract, cassia extract, paeoniflorin and syringic acid.

[0011] The composition for treating rosacea according to the present application adds ganoderma extract, cassia extract, paeoniflorin and syringic acid, which has the following technical effects: (1) The ganoderma extract, cortex moutan extract, paeoniflorin and cassia extract are designed around the TLR4-TNF-α inflammatory axis multiple target, to inhibit the expression of TLR4 and TNF-α, specifically: The ganoderma extract competitively binds to the extracellular domain of TLR4, prevents its activation, inhibits its expression, and can block the NF-κB / MAPK pathway to inhibit the expression of TNF-α from the source; The cortex moutan extract can down-regulate the TLR4 gene, and also directly promote the degradation of TNF-α protein to inhibit the expression of TLR4 and TNF-α; The paeoniflorin precisely targets the TLR4-MyD88 binding interface, and competitively binds to TNF-α to inhibit the expression of TNF-α; The cassia extract inhibits the endoplasmic reticulum-Golgi transport of TLR4, reduces the active TLR4 on the membrane surface, inhibits the expression of TLR4, and can break the positive feedback activation of TNF-α on TLR4, down-regulate miR-155, thereby indirectly inhibiting the expression of TNF-α.

[0012] In the composition for treating rosacea, the Ganoderma lucidum extract, the cortex moutan extract, the paeoniflorin, and the cinnamon extract block the "start-up-amplification" chain of inflammation by inhibiting the expression of TLR4 and TNF-α, so as to inhibit the recurrence of inflammation.

[0013] In addition, the syringic acid inhibits the NF-κB signaling pathway which is a key downstream pathway of the TLR4-TNF-α axis, scavenges reactive oxygen species (ROS which can activate the TLR4 inflammation axis), and reduces the expression of other pro-inflammatory factors (such as IL-1β and IL-6), thereby indirectly weakening the overactivation of the TLR4-TNF-α axis and assisting in relieving inflammation.

[0014] (2) The composition for treating rosacea can improve capillary dysfunction. In the experiment, the composition for treating rosacea was applied to the back of the mouse, and blood flow detection showed that the application of the composition for treating rosacea to the back of the mouse could effectively relieve the abnormal vascular generation at the rosacea lesion site, the abnormal vascular generation was less, and the capillary vasomotor nerve function was gradually restored, thereby relieving the persistent erythema and abnormal dilation of capillaries caused by rosacea.

[0015] (3) The composition for treating rosacea can effectively inhibit the growth of microorganisms. Cinnamtannin B1 (CB1) in the cinnamon extract is a condensed tannin with anti-inflammatory and antimicrobial activity, which can effectively kill Demodex folliculorum and inhibit the excessive proliferation of Demodex folliculorum; berberine in the coptis extract has a broad-spectrum antibacterial effect and can inhibit the growth and reproduction of various bacteria, such as Propionibacterium acnes which causes rosacea, and berberine can also inhibit inflammatory reactions and regulate the function of the immune system, which is helpful for preventing and treating rosacea.

[0016] Preferably, the mass parts of each component of the composition for treating rosacea are as follows: The cortex moutan extract is 10-40 parts; The Ganoderma lucidum extract is 10-40 parts; The coptis extract is 5-20 parts; The cinnamon extract is 5-20 parts; The paeoniflorin is 5-20 parts; The syringic acid is 5-20 parts.

[0017] More preferably, the mass parts of each component of the composition for treating rosacea are as follows: The cortex moutan extract is 20-25 parts; The Ganoderma lucidum extract is 20-25 parts; The coptis extract is 10-15 parts; The cinnamon extract is 10-15 parts; Paeoniflorin 10 ~ 15 parts; Syringic acid 10 ~ 15 parts.

[0018] Preferably, the composition for treating rose acne, wherein the content of berberine in the extract of coptis chinensis is 2.5% ~ 5%.

[0019] Preferably, the composition for treating rose acne, wherein the content of cinnamtannin B1 in the extract of cinnamomum cassia is 0.5% ~ 2%.

[0020] Preferably, the composition for treating rose acne, wherein the content of paeonol in the extract of cortex moutan is 1.5% ~ 2%.

[0021] Preferably, the composition for treating rose acne, wherein the content of ganoderic acid in the extract of ganoderma lucidum is 0.5% ~ 2%.

[0022] Preferably, the composition for treating rose acne, wherein the extract of cortex moutan, the extract of ganoderma lucidum and the extract of cinnamomum cassia are obtained by alcohol extraction.

[0023] The composition for treating rose acne, wherein the extract of coptis chinensis is obtained by distilled water extraction.

[0024] The application also provides a preparation method of the composition for treating rose acne, comprising the following steps: mixing the extract of cortex moutan, the extract of ganoderma lucidum, the extract of coptis chinensis, the extract of cinnamomum cassia, paeoniflorin and syringic acid in proportion to obtain the composition for treating rose acne.

[0025] The application also provides the use of the composition for treating rose acne in the preparation of a medicine for treating rose acne. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 The cytotoxicity of each component in the composition for treating rose acne is tested.

[0027] Figure 2 Example 1 provides the expression of TLR4 after the composition for treating rose acne is applied.

[0028] Figure 3 The appearance of the skin at the verification site is observed after the composition for treating rose acne obtained in the examples and comparative examples is applied to the back of the mouse.

[0029] Figure 4 The blood flow of the inflammatory part is detected after the composition for treating rose acne obtained in the examples and comparative examples is applied to the back of the mouse. DETAILED DESCRIPTION

[0030] The application will be further described in detail below in combination with the specific embodiments.

[0031] The preparation method of the cortex moutan extract used in each embodiment and the comparative example of the present application is as follows: the cortex moutan is ground into powder and sieved. Then 120 g of the powder is put into a solution of 1 L of ethanol and 1 L of acetone for ultrasonic treatment twice for 30 min, the supernatant is taken out, concentrated to dryness, and dissolved in the corresponding solvent for transfer to a small crystallizing bottle for natural drying. Then 1 g of the dried primary extract is dissolved in 2 mL of dimethyl sulfoxide (DMSO) for use.

[0032] The preparation method of the ganoderma extract used in each embodiment and the comparative example of the present application is as follows: 10 g of ganoderma is cut into pieces, 8 times the amount of 75% ethanol is used for reflux extraction twice for 1 h each time to prepare an alcohol extract of 1 g / ml of medicinal materials, which is stored in a refrigerator at 4°C for standby.

[0033] The preparation method of the coptis extract used in each embodiment and the comparative example of the present application is as follows: 100 g of dried coptis is added into distilled water in a ratio of 1:10 and 1:8 respectively for decoction twice, the filtrate is obtained after filtration with double-layered gauze, and the supernatant is obtained after centrifugation at 3000 r / min for 20 min.

[0034] The preparation method of the cinnamon extract used in each embodiment and the comparative example of the present application is as follows: the ultrasonic-assisted extraction method is used (the ratio of material to liquid is 1:20 g / mL, the extraction temperature is 40°C, the extraction time is 40 min, the ultrasonic power is 360 W, and the volume fraction of ethanol is 50%), the crude extract is dissolved in distilled water for standby after centrifugation (4200 r / min, 10 min) and vacuum rotary evaporation concentration (40°C) and drying.

[0035] The pure paeoniflorin used in each embodiment and the comparative example of the present application is Acmec with the product number P74652.

[0036] The pure syringic acid used in each embodiment and the comparative example of the present application is Acmec with the product number S62291.

[0037] Example 1 A composition for treating rosacea, comprising the following mass components: 23 parts of cortex moutan extract, the content of paeonol in the cortex moutan extract being 1.8%; 22 parts of ganoderma extract, the content of ganoderma acid in the ganoderma extract being 1.0%; 13 parts of coptis extract, the content of coptisine in the coptis extract being 3.5%; 12 parts of cinnamon extract, the content of cinnamon tannin B1 in the cinnamon extract being 1.2%; 12 parts of paeoniflorin; 13 parts of syringic acid.

[0038] The method for preparing the rose acne treating composition comprises the following steps: uniformly mixing the obtained cortex moutan extract, ganoderma lucidum extract, coptis chinensis extract, cinnamomum cassia extract, paeoniflorin and syringic acid in proportion to obtain the rose acne treating composition.

[0039] Embodiment 2 This embodiment is the second embodiment of the present application, which is different from the first embodiment in that the rose acne treating composition comprises the following mass components: 20 parts of cortex moutan extract, 20 parts of ganoderma lucidum extract, 10 parts of coptis chinensis extract, 15 parts of cinnamomum cassia extract, 10 parts of paeoniflorin; 15 parts of syringic acid.

[0040] Embodiment 3 This embodiment is the third embodiment of the present application, which is different from the first embodiment in that the rose acne treating composition comprises the following mass components: 25 parts of cortex moutan extract, 25 parts of ganoderma lucidum extract, 15 parts of coptis chinensis extract, 10 parts of cinnamomum cassia extract, 15 parts of paeoniflorin; 10 parts of syringic acid.

[0041] Embodiment 4 This embodiment is the fourth embodiment of the present application, which is different from the first embodiment in that the rose acne treating composition comprises the following mass components: 10 parts of cortex moutan extract with 2% content of paeonol, 10 parts of ganoderma lucidum extract with 2% content of ganoderic acid, 20 parts of coptis chinensis extract with 2.5% content of berberine, 5 parts of cinnamomum cassia extract with 2% content of cinnamtannin B1, 5 parts of paeoniflorin, 5 parts of syringic acid.

[0042] Embodiment 5 This embodiment is the fifth embodiment of the present application, which is different from the first embodiment in that the rose acne treating composition comprises the following mass components: 40 parts of cortex moutan extract with 1.5% content of paeonol, 40 parts of ganoderma lucidum extract with 0.5% content of ganoderic acid, 5 parts of coptis chinensis extract with 5% content of berberine, Cinnamon extract 20 parts, content of Cinnamon tannin B1 in the cinnamon extract 0.5%; Paeoniflorin 20 parts; Syringic acid 20 parts.

[0043] Example 6 This example is the 6th example of the present application, which is different from example 1 in that the therapeutic rose acne composition comprises the following mass components: Cortex moutan extract 50 parts, content of paeonol in the cortex moutan extract 1.0%; Ganoderma extract 50 parts, content of ganoderic acid in the ganoderma extract 0.2%; Rhizoma coptidis extract 3 parts, content of berberine in the rhizoma coptidis extract 6%; Cinnamon extract 25 parts, content of Cinnamon tannin B1 in the cinnamon extract 0.2%; Paeoniflorin 25 parts; Syringic acid 25 parts.

[0044] Example 7 This example is the 7th example of the present application, which is different from example 1 in that the therapeutic rose acne composition comprises the following mass components: Cortex moutan extract 5 parts, content of paeonol in the cortex moutan extract 3%; Ganoderma extract 5 parts, content of ganoderic acid in the ganoderma extract 3%; Rhizoma coptidis extract 25 parts, content of berberine in the rhizoma coptidis extract 2.0%; Cinnamon extract 3 parts, content of Cinnamon tannin B1 in the cinnamon extract 2.5%; Paeoniflorin 3 parts; Syringic acid 3 parts.

[0045] Comparative Example 1 This comparative example is the 1st comparative example of the present application, which is different from example 1 in that the therapeutic rose acne composition does not contain paeoniflorin.

[0046] Comparative Example 2 This comparative example is the 2nd comparative example of the present application, which is different from example 1 in that the therapeutic rose acne composition does not contain syringic acid.

[0047] Comparative Example 3 This comparative example is the 3rd comparative example of the present application, which is different from example 1 in that the therapeutic rose acne composition does not contain paeoniflorin and syringic acid.

[0048] Comparative Example 4 This comparative example is the 4th comparative example of the present application, which is different from example 1 in that the therapeutic rose acne composition does not contain ganoderma extract.

[0049] Comparative Example 5 This comparative example is the 5th comparative example of the present application, which is different from Example 1 in that the therapeutic rose acne composition does not contain the extract of Cinnamomum cassia.

[0050] Comparative Example 6 This comparative example is the 6th comparative example of the present application, which is different from Example 1 in that the therapeutic rose acne composition does not contain the extract of Ganoderma lucidum and the extract of Cinnamomum cassia.

[0051] Comparative Example 7 This comparative example is the 7th comparative example of the present application, which is different from Example 1 in that the therapeutic rose acne composition does not contain the extract of Cinnamomum cassia, paeoniflorin and syringic acid.

[0052] Performance test: (1) Cytotoxicity test The concentration of the therapeutic rose acne composition obtained in each example and comparative example is set to 1 mg / mL, 100 ug / mL, 10 ug / mL, 1 ug / mL and 100 ng / mL. The results are shown in Figure 1. Compared with the control group, the drugs in each group had no inhibitory effect on the viability of HaCaT cells at a concentration of 100 ug / ml. It is proved that each component has no toxicity to HaCaT cells at a concentration of 100 ug / ml or below.

[0053] (2) Expression level of TNF-α factor in cell experiment HaCaT cells in logarithmic growth phase were treated as follows: Normal control group: DMEM; LL-37 model group: treated with 12 uM LL-37 for 24 h; LL-37 + experimental drug administration group: the compound is the therapeutic rose acne composition obtained in each example and comparative example, and the compound is treated with DMEM medium containing LL-37 (100 ug / ml) for 24 h. After 24 h of compound action, the supernatant of HaCaT cells was collected, and the level of secreted protein TNF-α was detected by enzyme-linked immunosorbent assay (ELISA). The expression amount of inflammatory factor TNF-α of the therapeutic rose acne composition obtained in each example and comparative example is shown in Table 1.

[0054] (3) Inhibition of TLR4 factor in animal experiment Animal experiment a. Normal control group: intradermal injection of PBS 40 uL; b. Model group: intradermal injection of antibacterial peptide LL37 (320 uM) 40 uL; c. Administration group: intradermal injection of antibacterial peptide LL37 (320 uM) 40 uL, and application of 200 uL of the therapeutic acne rosacea composition of Example 1.

[0055] The immunostaining results show that, compared with the normal control group (CON), the expression of TLR4 in the lesion site of the LL37-induced model group is significantly increased. Compared with the model group (MOD), application of the therapeutic acne rosacea composition of Example 1 can effectively inhibit the expression of TLR4 Figure 2 . The rest of the examples have similar inhibitory effects Figure 2 .

[0056] (4) Pharmacodynamic evaluation of acne rosacea animal experiments (I) Appearance of back skin: Compared with the normal control group (CON), the back skin of the model group (MOD) mice has clear and obvious erythema with clear boundaries, proving that the modeling is successful. Figure 3 It can be seen that, compared with the normal control group, the blood flow of the back skin of the model group mice is significantly increased, indicating that the lesion site has obvious inflammation. Compared with the model group, application of 100 mpk of the therapeutic acne rosacea composition of Example 1 and Example 5 to the back can effectively relieve erythema, proving that the therapeutic acne rosacea composition of the present application can effectively relieve acne rosacea.

[0057] (II) Detection of back blood flow. Compared with the normal control group, the blood flow of the back skin of the model group mice is significantly increased, indicating that the lesion site has obvious inflammation. Figure 4 It can be seen that, compared with the model group, application of 100 mpk of the therapeutic acne rosacea composition of Example 1 and Example 6 to the back can effectively inhibit the blood flow of the blood vessels at the inflammation site, proving that the therapeutic acne rosacea composition of the present application can effectively relieve the angiogenesis at the lesion site of acne rosacea.

[0058] Table 1 Expression of inflammatory factor TNF-α in the therapeutic acne rosacea compositions of each example and the comparative example

[0059] Note: Compared with CON, ## P<0.01; compared with MOD, *P<0.05, **P<0.01 The above description is only an embodiment of the present application, and does not limit the scope of patent protection. Those skilled in the art can make non-substantial changes or substitutions on the basis of the present application, and still fall within the scope of patent protection.

Claims

1. A composition for treating rosacea, comprising an extract of cortex moutan and an extract of rhizoma coptidis, characterized in that, Also contains Ganoderma extract, Cinnamon extract, Paeonol and Syringic acid.

2. The therapeutic rosacea composition of claim 1, wherein, The mass parts of the components are: Cortex Moutan extract 10 ~ 40 parts; Ganoderma extract 10 ~ 40 parts; Rhizoma Coptidis extract 5 ~ 20 parts; Cinnamon extract 5 ~ 20 parts; Paeonol 5 ~ 20 parts; Syringic acid 5 ~ 20 parts.

3. The composition for treating rosacea according to claim 1, wherein The mass parts of the components are: Cortex Moutan extract 20 ~ 25 parts; Ganoderma extract 20 ~ 25 parts; Rhizoma Coptidis extract 10 ~ 15 parts; Cinnamon extract 10 ~ 15 parts; Paeonol 10 ~ 15 parts; Syringic acid 10 ~ 15 parts.

4. The composition for treating rosacea according to claim 1, wherein Rhizoma Coptidis extract contains berberine 2.5% ~ 5%.

5. The composition for treating rosacea according to claim 1, wherein Cinnamon extract contains Cinnamtannin B1 0.5% ~ 2.

6. The composition for treating rosacea according to claim 1, wherein Cortex Moutan extract contains Paeonol 1.5% ~ 2%.

7. The composition for treating rosacea according to claim 1, wherein Ganoderma extract contains Ganoderma acid 0.5% ~ 2%. Cortex Moutan extract, Ganoderma extract and Cinnamon extract are obtained by alcohol extraction.

8. The composition for treating rosacea according to claim 1, wherein Comprising the following steps:

9. A process for the preparation of a composition for the treatment of rosacea according to any of claims 1 to 8, characterized in that, Mixing Cortex Moutan extract, Ganoderma extract, Rhizoma Coptidis extract, Cinnamon extract, Paeonol and Syringic acid in proportion to obtain the therapeutic rose acne composition.

10. Use of the therapeutic rose acne composition of any one of claims 1 ~ 8 in the preparation of a therapeutic rose acne medicine. ​

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