CN111714475A - Use of and honokiol in the preparation of medicaments for treating and/or preventing rosacea - Google Patents

Abstract

The present invention provides the use of honokiol in preparing a medicament for treating and/or preventing rosacea. Experiments have shown that Honokiol can significantly reduce the erythema of rosacea mice, reduce the infiltration of inflammatory cells, reduce the number of inflammatory cells, and effectively treat rosacea. At the same time, after administration of honokiol to rosacea mice, there were no adverse reactions such as desquamation and weight loss, and no abnormality was found in the morphology of cells in various organs. Therefore, honokiol has a very good application prospect in the preparation of medicines for treating and/or preventing rosacea.

Description

Use of and honokiol in the preparation of medicaments for treating and/or preventing rosacea

technical field

The invention belongs to the field of medicine, in particular to the use of honokiol in the preparation of a medicine for treating and/or preventing rosacea.

Background technique

Rosacea is a chronic disease that primarily affects the facial skin and is characterized by inflammation and vascular-nerve hyperresponsiveness. Clinical features of rosacea include facial erythema, papules, and/or pustules, telangiectasia, and recurrent flushing, although it is not a A deadly disease that adversely affects the quality of life of rosacea sufferers.

Clinically, the treatment methods for rosacea are mostly topical drugs, such as tacrolimus ointment, fusidic acid cream, metronidazole gel, etc., but the treatment effect of these drugs is not good, easy to relapse, and may cause symptoms during use. There are adverse reactions of local irritation, causing damage to the skin and seriously affecting the quality of life of patients. Therefore, how to treat rosacea safely and effectively is still a difficult problem in the field of dermatology.

Therefore, it is of great significance to develop new drugs that can effectively treat rosacea without adverse reactions.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide the use of honokiol in the preparation of a medicament for treating and/or preventing rosacea.

The present invention provides the use of honokiol in the preparation of a medicament for treating and/or preventing rosacea.

Further, the medicine is an external preparation.

Further, the medicine is a liquid preparation, solid preparation, cream or cream for external use.

Further, in the liquid preparation for external use, the concentration of honokiol is 5%-10% mg/mL.

Further, the drug can improve skin erythema, reduce inflammatory cell infiltration, and/or reduce the number of inflammatory cells.

Further, the rosacea LL-37 induces rosacea.

The experimental results show that Honokiol can significantly reduce the erythema of rosacea mice, reduce the infiltration of inflammatory cells, reduce the number of inflammatory cells, and effectively treat rosacea. At the same time, after administration of honokiol to rosacea mice, there were no adverse reactions such as desquamation and weight loss, and no abnormality was found in the morphology of cells in various organs. And honokiol has a very good application prospect in the preparation of medicines for treating and/or preventing rosacea.

Obviously, according to the above-mentioned content of the present invention, according to the common technical knowledge and conventional means in the field, without departing from the above-mentioned basic technical idea of the present invention, other various forms of modification, replacement or change can also be made.

The above content of the present invention will be further described in detail below through the specific implementation in the form of examples. However, this should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention belong to the scope of the present invention.

Description of drawings

Figure 1 is the skin photos of the injection sites of each group, in which the NHK group represents and the honokiol group.

Figure 2 is the HE staining pathological pictures of mouse skin tissue in each group, in which the NHK group and the honokiol group are represented.

Detailed ways

The raw materials and equipment used in the present invention are all known products, obtained by purchasing commercially available products.

Therapeutic effect of Example 1 and honokiol on LL-37-induced rosacea

1. Experimental materials

1) Experimental drug: Honokiol was dissolved in butanediol into solutions (mg/mL) with a concentration of 0.5% and 1.0%; azelaic acid was dissolved in butanediol into a solution with a concentration of 15.0% (mg/mL).

2) Experimental animals: SPF grade BALB/c female mice (6 weeks old) and mouse-specific feed were purchased from Chengdu Dashuo Laboratory Animal Co., Ltd., and were fed in the laboratory for 1 week and adapted to the environment.

3) Main test reagents: Hematoxylin and eosin staining solutions were purchased from Zhuhai Baso Company; Honokiol was purchased from Shanghai San Chemical Technology Co., Ltd.; LL-37 was synthesized by Invivogen (San Diego, CA), USA, CAS No. 597562-32-8; base butanediol was purchased from Shanghai Demao Chemical Co., Ltd.

2. Experimental method

1) BALB/c mice were divided into 0.5% and honokiol group, 1.0% and honokiol group, 15.0% azelaic acid group, matrix group (ie butanediol group), LL-37 group (ie rosette). Acne animal model group) and blank group (n=9 in each group), mice were pretreated: experimental drugs were applied to the back skin of mice in the corresponding groups (about 0.1 ml/cm ² ), 2 times/day , a total of 6 days of administration; LL-37 group and blank group did not apply any preparations.

2) Modeling on the 4th day: intradermal injection of LL-37 (320 μM) in 0.5% and honokiol group, 1.0% and honokiol group, 15.0% azelaic acid group, matrix group and LL-37 group , the blank group was injected intradermally with ultrapure water, 50 μl every 12 hours, a total of 4 times.

3) The erythema was scored 12 hours after the last injection of LL-37/ultrapure water (ie, the sixth day after the drug was applied), and then the mice were sacrificed, and the skin of the back injection site was taken for tissue biopsy: a. Histopathological changes of mouse skin and counted inflammatory cells; b. During the experiment, observe the general condition of the mice, pay attention to whether there are adverse reactions, and take the various organs and tissues of the mice in the honokiol group and the blank group to make pathological sections and HE staining was used to observe the cell morphology of each organ.

3. Experimental results

1) Erythema score results

There was no erythema and edema in the skin of the mice in the blank group; the 0.5% and honokiol groups had pale erythema with blurred borders and slight edema; the 1.0% and honokiol groups had erythema and no obvious edema; the 15.0% azelaic acid group had borders. Blurred pale erythema without obvious edema; erythema with clear border and bright color with edema in the stroma group; erythema with clear border and darker color with obvious edema in the LL-37 group (Figure 1). From the erythema score results in Table 1, it can be seen that the erythema scores of the 1.0% and honokiol groups and the 15.0% azelaic acid group were significantly different from those of the matrix group and the LL-37 group, respectively (all P<0.05), 1.0 % and honokiol group and 15.0% azelaic acid group had no statistical difference (all P>0.05). It indicated that honokiol could significantly reduce the erythema score of LL-37-induced rosacea animal model, and had a significant therapeutic effect on rosacea, and the therapeutic effect increased with the increase of honokiol concentration.

Table 1 Comparison of erythema scores and inflammatory cell counts at skin injection sites in mice

Note: n=9. ^a : compared with the LL-37 group, p<0.05; ^b : compared with the matrix group, p<0.05; ^c : compared with the 15.0% azelaic acid group, p<0.05.

2) HE staining and inflammatory cell count results

HE staining showed that the epidermal structure of the blank group was intact, and the infiltration of inflammatory cells in the dermis was not obvious. In the 0.5% and honokiol group, 1.0% and honokiol group and 15.0% azelaic acid group, the epidermal structure was intact, and a small amount of inflammatory cell infiltration was seen in the dermis; the local epidermis was absent in the matrix group and LL-37 group, and blood vessels were seen in the dermis Expansion and more inflammatory cell infiltration, dominated by lymphocytes and neutrophils (Figure 2). Inflammatory cells were counted under a light microscope at ×400 magnification (the results are shown in Table 1): the counts of inflammatory cells in the 0.5% and honokiol groups and the 15.0% azelaic acid group were significantly lower than those in the LL-37 group (all P<0.05) , but there was no statistical difference compared with the matrix group (all P>0.05). The inflammatory cell counts in the 1.0% and honokiol groups were significantly lower than those in the stroma group and LL-37 group (p<0.05); and the inflammatory cell counts in the 1.0% and honokiol groups were significantly lower than those in the 15.0% azelaic acid group , there was a statistical difference (p<0.05). It can be seen that the number of inflammatory cells in the 0.5% and honokiol group was significantly less than that in the LL-37 group, with a statistical difference (P<0.05); the number of inflammatory cells in the 1.0% and honokiol group was significantly less than that in the matrix group, LL-37 group and 15.0% azelaic acid group had statistical difference (P<0.05), so Honokiol can significantly reduce the number of inflammatory cells in LL-37-induced rosacea animal model, and has a significant effect on rosacea. and the therapeutic effect increased with the increase of honokiol concentration.

3) Adverse reactions

The mice in each group were generally in good condition, and no adverse reactions such as desquamation and weight loss were found; no abnormality was found in the morphology of the cells of each organ and tissue in the neutralized honokiol group by HE staining.

The above results show that Honokiol can significantly reduce the erythema of rosacea mice, reduce the infiltration of inflammatory cells, reduce the number of inflammatory cells, and effectively treat rosacea. At the same time, after administration of honokiol to rosacea mice, there were no adverse reactions such as desquamation and weight loss, and no abnormality was found in the morphology of cells in various organs.

To sum up, the present invention provides the use of honokiol, honokiol or a mixture thereof in the preparation of a medicament for treating and/or preventing rosacea. Experiments have shown that Honokiol can significantly reduce the erythema of rosacea mice, reduce the infiltration of inflammatory cells, reduce the number of inflammatory cells, and effectively treat rosacea. At the same time, after administration of honokiol to rosacea mice, there were no adverse reactions such as desquamation and weight loss, and no abnormality was found in the morphology of cells in various organs. Therefore, honokiol has a very good application prospect in the preparation of medicines for treating and/or preventing rosacea.

Claims (6)

1. Use of honokiol in the preparation of a medicament for treating and/or preventing rosacea. 2. The use according to claim 1, wherein the medicine is an external preparation. 3. The use according to claim 2, wherein the medicine is a liquid preparation for external use, a solid preparation, a cream or a cream. 4 . The use according to claim 3 , wherein the concentration of honokiol in the liquid preparation for external use is 5% to 10% mg/mL. 5 . 5. The use according to any one of claims 1-4, wherein the drug can improve skin erythema, reduce inflammatory cell infiltration, and/or reduce the number of inflammatory cells. 6. The use according to any one of claims 1-4, wherein the rosacea is LL-37-induced rosacea.

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