Composition for treating inflammatory skin diseases, preparation method and application

Abstract

The invention discloses a composition for treating inflammatory skin diseases, a preparation method and application, the inflammatory skin diseases comprise psoriasis and atopic dermatitis, and the composition comprises methotrexate, transdermal peptide and cerium substituted molybdenum polyoxometallate. The MTX-coated CMB-TD-1 has the advantages that an immunomodulator methotrexate (MTX) is loaded, the transdermal peptide (TD-1) is used for surface modification, the obtained MTX-coated CMB-TD-1 has reliable biological safety, the loaded MTX can inhibit abnormal activated inflammatory reaction, meanwhile, CMB endows the MTX-coated CMB-TD-1 with excellent active oxygen scavenging capacity, and transdermal drug delivery can be achieved through the surface modified TD-1.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a composition for treating inflammatory skin diseases, a preparation method and application thereof. Background Art

[0002] Psoriasis, commonly known as psoriasis, is one of the most common chronic recurrent inflammatory skin diseases. It has a long course and is prone to relapse. The clinical manifestations are mainly erythema and scaling. It can occur all over the body, but is more common on the scalp and extensor side of the limbs. It often worsens in winter. The etiology is complex, and the pathogenesis of psoriasis is not very clear. Current studies have found that the onset of psoriasis is related to tumor necrosis factor-α and its related cytokines. A large number of studies have also shown that the occurrence of psoriasis is closely related to the production of reactive oxygen species. At present, it has been reported that natural products or antioxidants can be used to reduce the level of reactive oxygen species in psoriasis for the treatment of psoriasis.

[0003] Atopic dermatitis is a chronic, recurrent, inflammatory skin disease, with recurrent chronic eczematous rashes as the main clinical manifestation, accompanied by significant dryness and itching of the skin. Because patients often have other atopic diseases such as allergic rhinitis and asthma, it is considered a systemic disease. Atopic dermatitis is currently incurable and can seriously affect the quality of life. However, effective and standardized treatment can relieve symptoms and reduce recurrences.

[0004] In recent years, polyoxometalates (POMs) have developed rapidly in the field of biological applications. Polyoxometalates refer to a class of metal oxygen cluster compounds with special properties and structures formed by the aggregation of some transition metal elements. Based on this, many literatures have applied POMs to inflammatory bowel disease, acute kidney injury and other inflammatory-related diseases, and have achieved good therapeutic effects. Molybdenum-based polyoxometalate (POM) nanoclusters are polyoxometalates containing at least molybdenum ions. Under certain reducing or oxidizing conditions, the Mo ions in POMs are in the form of Mo 5+ and Mo 6+ The valence states of these molecules change at any time, and they can react quickly with reactive oxygen species (ROS) to remove ROS in local tissues, thereby alleviating inflammation and tissue damage caused by inflammation. However, a higher concentration is required to effectively inhibit the level of ROS in cells, so the treatment efficiency is not high. Summary of the invention

[0005] The purpose of the present invention is to provide a composition, preparation method and application for treating inflammatory skin diseases in view of the deficiencies in the prior art, so as to solve the problem of low treatment efficiency existing in the related art.

[0006] To achieve the above object, the technical solution adopted by the present invention is:

[0007] In a first aspect, a composition for treating inflammatory skin diseases is provided, comprising methotrexate, a transdermal peptide, and a cerium-substituted molybdenum-based polyoxometalate;

[0008] Wherein, the inflammatory skin diseases include psoriasis and atopic dermatitis.

[0009] In some of the embodiments, the ratio of the mass of the methotrexate, the mass of the transdermal peptide and the mass of the cerium-substituted molybdenum-based polyoxometalate is (10-20): (20-30): 2.4.

[0010] In a second aspect, a preparation method is provided for preparing the composition for treating inflammatory skin diseases as described in the first aspect, comprising:

[0011] A mixed solution containing methotrexate, transdermal peptide and cerium-substituted molybdenum-based polyoxometalate is prepared.

[0012] In some of the embodiments, including:

[0013] preparing a first solution containing methotrexate;

[0014] preparing a second solution containing a transdermal peptide;

[0015] preparing a third solution containing a cerium-substituted molybdenum-based polyoxometalate;

[0016] The first solution, the second solution and the third solution are mixed to obtain a mixed solution, wherein the mixed solution is a composition for treating inflammatory skin diseases.

[0017] In some embodiments, in the first solution, the concentration of methotrexate is 9-11 μg / μL.

[0018] In some embodiments, in the second solution, the concentration of the transdermal peptide is 90-110 μg / μL.

[0019] In some of the embodiments, in the third solution, the concentration of the cerium-substituted molybdenum-based polyoxometalate is 11-13 μg / μL.

[0020] In some of the embodiments, the ratio of the volume of the first solution, the volume of the second solution and the volume of the third solution is (27-33):(4.5-5.5):4.

[0021] In some of the embodiments, in the mixed solution, the ratio of the mass of the methotrexate, the mass of the transdermal peptide and the mass of the cerium-substituted molybdenum-based polyoxometalate is (10-20): (20-30): 2.4.

[0022] In some of the embodiments, including:

[0023] Dissolving methotrexate in dimethyl sulfoxide to obtain a first solution, wherein the concentration of methotrexate in the first solution is 9-11 μg / μL;

[0024] Dissolving the transdermal peptide in sterile physiological saline to obtain a second solution, wherein the concentration of the transdermal peptide in the second solution is 90-110 μg / μL;

[0025] Dissolving the cerium-substituted molybdenum-based polyoxometalate in sterile water to obtain a third solution, wherein the concentration of the cerium-substituted molybdenum-based polyoxometalate in the third solution is 11-13 μg / μL;

[0026] The first solution, the second solution and the third solution are mixed in a volume ratio of (27-33):(4.5-5.5):4 to obtain a mixed solution.

[0027] In some of the embodiments, including:

[0028] Dissolving methotrexate in dimethyl sulfoxide to obtain a first solution, wherein the concentration of methotrexate in the first solution is 10 μg / μL;

[0029] Dissolving the transdermal peptide in sterile physiological saline to obtain a second solution, wherein the concentration of the transdermal peptide in the second solution is 100 μg / μL;

[0030] Dissolving the cerium-substituted molybdenum-based polyoxometalate in sterile water to obtain a third solution, wherein the concentration of the cerium-substituted molybdenum-based polyoxometalate in the third solution is 12 μg / μL;

[0031] The first solution, the second solution and the third solution are mixed in a volume ratio of 30:5:4 to obtain a mixed solution.

[0032] In some embodiments, the preparation method of the cerium-substituted molybdenum-based polyoxometalate comprises:

[0033] preparing a mixed solution containing an inorganic cerium salt, a reducing agent, an inorganic acid and a molybdate, wherein the mixed solution is acidic;

[0034] The mixed solution is dried to obtain cerium-substituted molybdenum-based polyoxometalate.

[0035] In some of the embodiments, including:

[0036] Dissolving CeCl3·7H2O and hydrazine hydrochloride in deionized water to obtain a first mixed solution, wherein the ratio of the mass of CeCl3·7H2O to the volume of deionized water is (3.6-4.4):1, and the ratio of the mass of hydrazine hydrochloride to the volume of deionized water is (2.7-3.3):5;

[0037] adding HCl to the first mixed solution to obtain a second mixed solution, wherein the concentration of the added HCl is 0.07-0.08 M;

[0038] Adding Na2MoO4·2H2O to the second mixed solution to obtain a mixed solution, wherein the ratio of the mass of Na2MoO4·2H2O to the volume of deionized water is (9-11):1;

[0039] The mixed solution is placed in a controlled evaporation state, and a dark blue CMB solution is obtained after 2-4 days;

[0040] The CMB solution was freeze-dried and stored.

[0041] In some of the embodiments, including:

[0042] Dissolving CeCl3·7H2O in deionized water to obtain a first solution, wherein the ratio of the mass of CeCl3·7H2O to the volume of the deionized water is (18-22):1;

[0043] Dissolving hydrazine hydrochloride in deionized water to obtain a second solution, wherein the ratio of the mass of hydrazine hydrochloride to the volume of deionized water is (2.7-3.3):1;

[0044] Dissolving Na2MoO4·2H2O in deionized water to obtain a third solution, wherein the ratio of the mass of Na2MoO4·2H2O to the volume of the deionized water is (45-55):1;

[0045] The first solution, the second solution and deionized water are mixed to obtain a first mixed solution, wherein the ratio of the volume of the deionized water, the volume of the first solution and the volume of the second solution is (1.8-2.2):(0.9-1.1):1;

[0046] adding HCl to the first mixed solution to obtain a second mixed solution, wherein the concentration of the added HCl is 0.09-0.11 M;

[0047] Mixing the third solution with the second mixed solution to obtain a mixed solution, wherein the ratio of the volume of the third solution to the volume of deionized water is (0.9-1.1):2;

[0048] The mixed solution is placed in a controlled evaporation state, and a dark blue CMB solution is obtained after 2-4 days;

[0049] The CMB solution was freeze-dried and stored.

[0050] In a third aspect, there is provided a use of the material composition as described in the first aspect or the composition prepared by the preparation method as described in the second aspect in preparing a drug for treating inflammatory skin diseases.

[0051] The present invention adopts the above technical solution, and has the following technical effects compared with the prior art:

[0052] The present invention provides a composition for treating inflammatory skin diseases, a preparation method and an application thereof, wherein the composition is loaded with an immunomodulator methotrexate (MTX) and surface-modified with a transdermal peptide (TD-1), and the obtained MTX@CMB-TD-1 has reliable biosafety, and the loaded MTX can inhibit abnormally activated inflammatory reactions, while CMB gives it excellent reactive oxygen scavenging ability, and the surface-modified TD-1 can achieve transdermal administration; the components in the MTX@CMB-TD-1 of the present invention work synergistically, and CMB has the ability to efficiently remove ROS and can assist in inhibiting inflammatory reactions, while CMB nanoclusters form a self-assembled microvesicle structure in an aqueous solution to encapsulate the loaded immunomodulator MTX; TD1 outside the microvesicle can be adsorbed on the surface of the CMB microvesicle under the action of the attraction of positive and negative charges, and exert a transdermal effect; MTX exerts an immunomodulatory function after transdermal administration, and effectively inhibits abnormal inflammatory activation. Through reasonable design, the MTX@CMB-TD-1 of the present invention can achieve TD-1-mediated skin external application, and combined with the dual mechanisms of ROS scavenging and MTX immunoregulation, it can achieve comprehensive and efficient anti-inflammatory effects, thereby achieving a therapeutic effect on psoriasis or atopic dermatitis; the MTX@CMB-TD-1 drug-loaded microvesicle system of the present invention is easy to prepare (CMB material can be assembled into a vesicle structure in an aqueous solution), easy to degrade (after entering the tissue, the CMB vesicle can release MTX in a dynamic self-assembly-disaggregation process, and at the same time be cleared by the body in a monomer form, and will not remain in the tissue like other insoluble nanoparticles), and the surface-bound transdermal peptide TD-1 can help achieve more effective transdermal administration. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 These are photos of psoriasis-like skin inflammation in mice of different groups in Example 5;

[0054] Figure 2 These are photos of atopic dermatitis in mice of different groups in Example 6. DETAILED DESCRIPTION

[0055] In order to make the purpose, technical solutions and advantages of the present application clearer, the present application is described and illustrated below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not intended to limit the present application. Based on the embodiments provided in the present application, all other embodiments obtained by ordinary technicians in the field without making creative work are within the scope of protection of the present application.

[0056] Example 1

[0057] This embodiment relates to the composition, preparation method and application of the present invention for treating inflammatory skin diseases.

[0058] A composition for treating inflammatory skin diseases comprises methotrexate (MTX), a transdermal peptide (TD-1) and a cerium-substituted molybdenum-based polyoxometalate (CMB).

[0059] In the present invention, inflammatory skin diseases include psoriasis and atopic dermatitis.

[0060] In some of the embodiments, the ratio of the mass of MTX, the mass of TD-1 and the mass of CMB is (10-20):(20-30):2.4.

[0061] Preferably, the ratio of the mass of MTX, the mass of TD-1 and the mass of CMB is 75:125:12.

[0062] In some of these embodiments, the composition is in the form of a solution.

[0063] For the above composition, its preparation method is as follows:

[0064] S1. Prepare a mixed solution containing methotrexate, transdermal peptide, and cerium-substituted molybdenum-based polyoxometalate.

[0065] Further, step S1 includes:

[0066] S11. Preparing a first solution containing methotrexate;

[0067] S12. Preparing a second solution containing a transdermal peptide;

[0068] S13. Preparing a third solution containing a cerium-substituted molybdenum-based polyoxometalate;

[0069] S14. Mix the first solution, the second solution, and the third solution to obtain a mixed solution, wherein the mixed solution is a composition (MTX@CMB-TD-1) for treating inflammatory skin diseases.

[0070] In step S11, in the first solution, the concentration of MTX is 9-11 μg / μL.

[0071] Preferably, the concentration of MTX is 10 μg / μL.

[0072] In step S11, the solvent is dimethyl sulfoxide (DMSO).

[0073] In step S12, in the second solution, the concentration of TD-1 is 90-110 μg / μL.

[0074] Preferably, the concentration of TD-1 is 100 μg / μL.

[0075] In step S12, the solvent is sterile saline.

[0076] In step S13, in the third solution, the concentration of CMB is 11-13 μg / μL.

[0077] Preferably, the concentration of CMB is 12 μg / μL.

[0078] In step S13, the solvent is sterile water.

[0079] In step S14, the ratio of the volume of the first solution, the volume of the second solution and the volume of the third solution is (27-33):(4.5-5.5):4.

[0080] Preferably, the ratio of the volume of the first solution, the volume of the second solution and the volume of the third solution is 30:5:4.

[0081] In step S14, in the mixed solution, the ratio of the mass of MTX, the mass of TD-1 and the mass of CMB is (10-20): (20-30): 2.4.

[0082] Furthermore, after step S14, the method further includes:

[0083] S15. Dilute the mixture.

[0084] In step S15, the mixed solution is diluted with sterile saline.

[0085] In step S15, the ratio of the volume of the sterile physiological saline to the volume of the mixed solution is 8-12.

[0086] Preferably, the ratio of the volume of the sterile physiological saline to the volume of the mixed solution is 9-10.

[0087] The present invention also provides an application of the above-mentioned composition in the preparation of a medicine for treating inflammatory diseases.

[0088] Specifically, the inflammatory diseases include, but are not limited to: dermatomyositis, Grave's disease, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus (SLE), sarcoidosis, Sjögren's syndrome, amyloidosis, Hashimoto's thyroiditis, vasculitis, rheumatoid arthritis, reactive arthritis, polymyositis, scleroderma, Addison's disease, vitiligo, pernicious anemia, glomerulonephritis, severe celiac disease, type 1 diabetes, psoriasis and pulmonary fibrosis, ulcerative colitis, Crohn's disease, atopic dermatitis.

[0089] Preferably, the inflammatory disease is psoriasis or atopic dermatitis.

[0090] In particular, the inflammatory disease is associated with elevated levels of inflammatory factors that stimulate cells to generate reactive oxygen species (ROS).

[0091] Specifically, the inflammatory factor is one or more of CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8 and IL36G.

[0092] Specifically, the increased level of the inflammatory factor is caused by the stimulation of TNF-α.

[0093] Example 2 Preparation of MTX@CMB-TD-1

[0094] MTX was dissolved in DMSO to prepare a 10 μg / μL MTX solution, TD-1 was dissolved in sterile saline to prepare a 100 μg / μL TD-1 solution, and CMB was dissolved in sterile water to prepare a 12 μg / μL CMB solution. The obtained MTX, CMB and TD-1 solutions were then mixed in a ratio of 30:4:5 to obtain a light green suspension, namely MTX@CMB-TD-1.

[0095] Example 3 Preparation of cerium-substituted molybdenum-based polyoxometalate (CMB)

[0096] Dissolve 20 mg CeCl3·7H2O and 3 mg hydrazine hydrochloride in 5 ml water, then add 0.4 ml 1 M HCl with stirring;

[0097] While maintaining stirring, add 50 mg of Na2Mo4·2H2O to the mixture;

[0098] Continue stirring for 10-20 minutes to obtain a clear dark blue solution;

[0099] Then it was transferred to a 20 ml vial sealed with a metal cap having a rubber septum, and the rubber septum was pierced with a hollow needle with an inner diameter of 1.2 mm, so that the clear dark blue solution transferred to the bottle was placed in a state of controlled evaporation and heated at 100 °C in an oven to obtain a dark blue CMB solution after 3 days;

[0100] Store it freeze-dried.

[0101] Example 4 Preparation of Ce-Substituted Molybdenum-Based Polyoxometalate (CMB)

[0102] Weigh 20 mg of CeCl3·7H2O, 3 mg of hydrazine hydrochloride, and 50 mg of Na2MoO4·2H2O, and dissolve them in 1 ml of water to obtain 1 ml of each of the three solutions;

[0103] Take 2 mL of deionized water, add 1 mL of the aforementioned CeCl3 solution and 1 mL of the aforementioned hydrochloric acid hydrazine solution under stirring;

[0104] While maintaining stirring, add 0.4 mL of 1 M HCl;

[0105] While maintaining stirring, add 1 mL of the aqueous solution containing Na2MoO4 described above dropwise to the mixture;

[0106] Continue stirring for 10-20 minutes to obtain a clear dark blue solution;

[0107] This was transferred to a 20-mL vial sealed with a metal cap with a rubber septum;

[0108] The rubber septum was pierced with a hollow needle with an inner diameter of 1.2 mm to put the sample in a state of controlled evaporation;

[0109] After heating at 100 °C in an oven for 3 days, a dark blue solution containing CMB was obtained;

[0110] It was freeze-dried and stored for later use.

[0111] Example 5 MTX@CMB-TD-1 inhibits IMQ-induced psoriasis-like skin inflammation in mice

[0112] First, an IMQ-induced psoriasis mouse model was constructed: the same operation as in Example 6.

[0113] MTX solution, TD-1 solution, CMB solution and MTX@CMB-TD-1 were prepared according to the operation of Example 2.

[0114] When administering the drug, take 3.9 μL of MTX@CMB-TD-1 per mouse, dilute it to 40 μL with sterile saline, and carefully apply it to the skin of the modeling area of ​​the mouse after the mouse is anesthetized. After the skin is fully dried, put the mouse back into the cage. The time interval between administration and modeling is at least 6 hours. The skin of normal mice was used as the control group (G1).

[0115] result( Figure 1): It can be seen that on the 6th day of IMQ modeling, the IMQ modeling group (G2) and IMQ+TD-1 (G4) showed obvious psoriasis-like skin lesions, manifested as skin thickening, a large number of scales, and erythema; the erythema of the IMQ+MTX group (G3) and IMQ+MTX+TD-1 group (G5) was alleviated, but there was still obvious skin thickening and a large number of scales; the IMQ+CMB+TD-1 group (G6) showed a certain therapeutic effect, with reduced skin scales and slightly alleviated erythema, but there were still certain psoriasis-like skin lesions; and the application of MTX@CMB-TD-1 (G7) effectively inhibited the progression of IMQ-induced psoriasis-like skin inflammation, and scales, keratin thickening and erythema were not obvious, showing an excellent therapeutic effect.

[0116] Example 6 MTX@CMB-TD-1 inhibits MC903-induced atopic dermatitis in mice

[0117] First, an MC903-induced atopic dermatitis mouse model was constructed: the same operation as in Example 8.

[0118] MTX solution, TD-1 solution, CMB solution and MTX@CMB-TD-1 were prepared according to the operation of Example 2.

[0119] When administering the drug, take 3.9 μL of MTX@CMB-TD-1 per mouse, dilute it to 40 μL with sterile saline, and carefully apply it to the skin of the modeling area of ​​the mouse after the mouse is anesthetized. After the skin is fully dried, put the mouse back into the cage. The time interval between administration and modeling is at least 6 hours. The skin of normal mice was used as the control group (G1).

[0120] result( Figure 2 ): It can be seen that on the 6th day of MC903 modeling, the MC903 modeling group (G2) and MC903+TD-1 (G4) showed obvious atopic dermatitis-like skin lesions, manifested as skin thickening, erythema, and scaling; the scaling of the MC903+MTX group (G3) and the MC903+MTX+TD-1 group (G5) was reduced, but there was still obvious skin thickening and erythema; the MC903+CMB+TD-1 group (G6) showed a certain therapeutic effect, with reduced erythema and scaling, but there were still certain atopic dermatitis-like skin lesions; and the application of MTX@CMB-TD-1 (G7) effectively inhibited the progression of MC903-induced atopic dermatitis-like skin inflammation, and scaling, skin thickening and erythema were not obvious, showing an excellent therapeutic effect.

[0121] The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the description and illustrations of the present invention should be included in the protection scope of the present invention.

Claims

1. A composition for treating inflammatory skin diseases, characterized in that: These include methotrexate, transdermal peptides, and cerium-substituted molybdenum-based polyoxometalates; Wherein, the inflammatory skin diseases include psoriasis and atopic dermatitis.

2. The composition according to claim 1, characterized in that The ratio of the mass of the methotrexate, the mass of the transdermal peptide and the mass of the cerium-substituted molybdenum-based polyoxometalate is (10-20): (20-30): 2.

4.

3. A preparation method for preparing a composition for treating inflammatory skin diseases as claimed in any one of claims 1 to 2, characterized in that: include: A mixed solution containing methotrexate, transdermal peptide and cerium-substituted molybdenum-based polyoxometalate is prepared.

4. The preparation method according to claim 3, characterized in that: include: preparing a first solution containing methotrexate; preparing a second solution containing a transdermal peptide; preparing a third solution containing a cerium-substituted molybdenum-based polyoxometalate; The first solution, the second solution and the third solution are mixed to obtain a mixed solution, wherein the mixed solution is a composition for treating inflammatory skin diseases.

5. The preparation method according to claim 4, characterized in that: In the first solution, the concentration of methotrexate is 9-11 μg / μL; and / or In the second solution, the concentration of the transdermal peptide is 90-110 μg / μL; and / or In the third solution, the concentration of the cerium-substituted molybdenum-based polyoxometalate is 11-13 μg / μL; and / or The ratio of the volume of the first solution, the volume of the second solution and the volume of the third solution is (27-33): (4.5-5.5): 4; and / or In the mixed solution, the ratio of the mass of the methotrexate, the mass of the transdermal peptide and the mass of the cerium-substituted molybdenum-based polyoxometalate is (10-20): (20-30): 2.

4.

6. The preparation method according to claim 4 or 5, characterized in that: include: Dissolving methotrexate in dimethyl sulfoxide to obtain a first solution, wherein the concentration of methotrexate in the first solution is 9-11 μg / μL; Dissolving the transdermal peptide in sterile physiological saline to obtain a second solution, wherein the concentration of the transdermal peptide in the second solution is 90-110 μg / μL; Dissolving the cerium-substituted molybdenum-based polyoxometalate in sterile water to obtain a third solution, wherein the concentration of the cerium-substituted molybdenum-based polyoxometalate in the third solution is 11-13 μg / μL; The first solution, the second solution and the third solution are mixed in a volume ratio of (27-33):(4.5-5.5):4 to obtain a mixed solution.

7. The preparation method according to claim 6, characterized in that: include: Dissolving methotrexate in dimethyl sulfoxide to obtain a first solution, wherein the concentration of methotrexate in the first solution is 10 μg / μL; Dissolving the transdermal peptide in sterile physiological saline to obtain a second solution, wherein the concentration of the transdermal peptide in the second solution is 100 μg / μL; Dissolving the cerium-substituted molybdenum-based polyoxometalate in sterile water to obtain a third solution, wherein the concentration of the cerium-substituted molybdenum-based polyoxometalate in the third solution is 12 μg / μL; The first solution, the second solution and the third solution are mixed in a volume ratio of 30:5:4 to obtain a mixed solution.

8. The preparation method according to claim 3, characterized in that: The preparation method of cerium-substituted molybdenum-based polyoxometalate comprises: preparing a mixed solution containing an inorganic cerium salt, a reducing agent, an inorganic acid and a molybdate, wherein the mixed solution is acidic; The mixed solution is dried to obtain cerium-substituted molybdenum-based polyoxometalate.

9. The preparation method according to claim 7 or 8, characterized in that: include Dissolving CeCl3·7H2O and hydrazine hydrochloride in deionized water to obtain a first mixed solution, wherein the ratio of the mass of CeCl3·7H2O to the volume of deionized water is (3.6-4.4):1, and the ratio of the mass of hydrazine hydrochloride to the volume of deionized water is (2.7-3.3):5; adding HCl to the first mixed solution to obtain a second mixed solution, wherein the concentration of the added HCl is 0.07-0.08 M; Adding Na2MoO4·2H2O to the second mixed solution to obtain a mixed solution, wherein the ratio of the mass of Na2MoO4·2H2O to the volume of deionized water is (9-11):1; The mixed solution is placed in a controlled evaporation state, and a dark blue CMB solution is obtained after 2-4 days; freeze-drying the CMB solution and storing it; or Dissolving CeCl3·7H2O in deionized water to obtain a first solution, wherein the ratio of the mass of CeCl3·7H2O to the volume of the deionized water is (18-22):1; Dissolving hydrazine hydrochloride in deionized water to obtain a second solution, wherein the ratio of the mass of hydrazine hydrochloride to the volume of deionized water is (2.7-3.3):1; Dissolving Na2MoO4·2H2O in deionized water to obtain a third solution, wherein the ratio of the mass of Na2MoO4·2H2O to the volume of the deionized water is (45-55):1; The first solution, the second solution and deionized water are mixed to obtain a first mixed solution, wherein the ratio of the volume of the deionized water, the volume of the first solution and the volume of the second solution is (1.8-2.2):(0.9-1.1):1; adding HCl to the first mixed solution to obtain a second mixed solution, wherein the concentration of the added HCl is 0.09-0.11 M; Mixing the third solution with the second mixed solution to obtain a mixed solution, wherein the ratio of the volume of the third solution to the volume of deionized water is (0.9-1.1):2; The mixed solution is placed in a controlled evaporation state, and a dark blue CMB solution is obtained after 2-4 days; The CMB solution was freeze-dried and stored.

10. Use of the composition according to any one of claims 1 to 2 or the composition prepared by the preparation method according to any one of claims 3 to 9 in preparing a drug for treating inflammatory skin diseases.

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