Application of diacerein and derivative thereof in preparation of medicine for inhibiting fibrosis and promoting local tissue regeneration

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of diacerein and derivatives thereof in preparation of medicines for inhibiting fibrosis and promoting local tissue regeneration. The medicine for inhibiting fibrosis and / or promoting local tissue regeneration is prepared from diacerein and the derivative thereof, so that fibrosis induced by a biological material, the immune cell infiltration degree and tissue calcification can be resisted, the wound regeneration healing speed can be increased, and meanwhile, the effects of resisting fibrosis and promoting local tissue regeneration are achieved.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to the application of diacerein and its derivatives in preparing medicines for inhibiting fibrosis and promoting local tissue regeneration. Background Art

[0002] As a foreign body, biomaterials can induce chronic and acute inflammation in the body. The presence of acute inflammation may lead to implantation failure, and chronic inflammation may affect the characteristics of regenerated tissue. Therefore, it is necessary to control such abnormal reactions induced by the implantation of biomaterials. However, the necessary immune response is also crucial for normal tissue repair. In the past, broad-spectrum immunosuppressive drugs comprehensively inhibited the inflammatory response and impaired regeneration and repair. In general, fibrosis is a tissue repair process, but excessive fibrosis reactions can lead to tissue damage and dysfunction. Therefore, it is necessary to find new drugs with selective immunomodulatory capabilities to inhibit biomaterial-related inflammatory reactions and promote local tissue regeneration. Summary of the invention

[0003] In order to solve the deficiencies of the prior art, the present invention provides an application of diacerein and its derivatives in the preparation of a drug for inhibiting fibrosis and promoting local tissue regeneration.

[0004] The technical solution provided by the present invention is as follows:

[0005] A use of diacerein and its derivatives in preparing a drug for inhibiting fibrosis, wherein the diacerein and its derivatives have the following general structural formula:

[0006]

[0007] in:

[0008] R1 is a straight or branched chain alkyl group of 1 to 6 carbon atoms;

[0009] R2 is a straight or branched alkyl group of 1 to 6 carbon atoms;

[0010] R3 is hydrogen or a straight or branched chain alkyl group of 1 to 6 carbon atoms;

[0011] R1, R2 and R3 are the same or different;

[0012] The fibrosis is fibrosis induced by biomaterials.

[0013] The inventors have found that diacerein and its derivatives can resist fibrosis, immune cell infiltration and tissue calcification induced by biomaterials, and exhibit acute or chronic inflammation caused by biomaterials.

[0014] Preferably, R1 is methyl, R2 is methyl, and R3 is hydrogen, that is, diacerein, with the following structural formula:

[0015]

[0016] Specifically, the drug is in the form of oral capsules, intravenous injections, external ointments or sprays.

[0017] Specifically, the dosage of the drug is 0 to 100 mg / ml (not zero), that is, the concentration in the action area.

[0018] The present invention also provides an application of diacerein and its derivatives in the preparation of a drug for promoting local tissue regeneration. The diacerein and its derivatives have the following general structural formula:

[0019]

[0020] in:

[0021] R1 is a straight or branched alkyl group of 1 to 6 carbon atoms;

[0022] R2 is a straight or branched alkyl group of 1 to 6 carbon atoms;

[0023] R3 is hydrogen or a straight or branched chain alkyl group of 1 to 6 carbon atoms;

[0024] R1, R2 and R3 are the same or different;

[0025] The local tissue includes hair follicles and appendages in the process of wound healing.

[0026] The inventors have discovered that diacerein and its derivatives can increase the speed of wound regeneration and healing and promote local tissue regeneration.

[0027] Preferably, R1 is methyl, R2 is methyl, and R3 is hydrogen.

[0028] Specifically, the drug is in the form of oral capsules, intravenous injections, external ointments or sprays.

[0029] Specifically, the dosage of the drug is 0 to 100 mg / ml (not zero).

[0030] The present invention also provides a use of diacerein and its derivatives in preparing a drug for inhibiting fibrosis and promoting local tissue regeneration. The diacerein and its derivatives have the following general structural formula:

[0031]

[0032] in:

[0033] R1 is a straight or branched alkyl group of 1 to 6 carbon atoms;

[0034] R2 is a straight or branched alkyl group of 1 to 6 carbon atoms;

[0035] R3 is hydrogen or a straight or branched chain alkyl group of 1 to 6 carbon atoms;

[0036] R1, R2 and R3 are the same or different;

[0037] The fibrosis is fibrosis induced by biomaterials;

[0038] The local tissue includes hair follicles and appendages in the process of wound healing.

[0039] The inventors have found that diacerein and its derivatives can not only resist biomaterial-induced fibrosis, immune cell infiltration and tissue calcification, but also increase the speed of wound regeneration and healing, while playing the role of resisting fibrosis and promoting local tissue regeneration.

[0040] Preferably, R1 is methyl, R2 is methyl, and R3 is hydrogen.

[0041] Specifically, the drug is in the form of oral capsules, intravenous injections, external ointments or sprays.

[0042] Specifically, the dosage of the drug is 0 to 100 mg / ml (not zero).

[0043] Specifically, the drug includes pharmaceutically acceptable carriers and excipients.

[0044] Furthermore, the drug also includes any one or more of an absorption promoter, a surfactant or a synergist.

[0045] Furthermore, the drug is physically blended with biomaterials, or delivered by drug-carrying methods such as chemical cross-linking, so as to provide a sustained or short-term therapeutic effect, and inhibit foreign body reactions and promote regeneration by combining with materials.

[0046] The beneficial effects of the present invention are as follows:

[0047] The active ingredients involved in the present invention include not only diacerein, but also derivatives having similar functions or structures to diacerein;

[0048] By using the method of the present invention, the occurrence of material-induced fibrosis can be effectively inhibited and the regeneration of local tissue can be promoted. In the experiment, the biomaterial containing diacerein had a weaker inflammatory response, significantly reduced fibrosis, and obvious signs of tissue regeneration;

[0049] By using the method of the present invention, the use of biomaterials containing diacerein has lower capsule thickness, reduced inflammation levels and more obvious signs of tissue regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 This is a rendering of an implant containing diacerein material.

[0051] Figure 2 This is a comparison chart of wound regeneration and healing speed in the diacerein group.

[0052] Figure 3 This is a comparison chart of hair follicle regeneration in the wound of the diacerein group. DETAILED DESCRIPTION

[0053] The principles and features of the present invention are described below. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0054] Unless otherwise specified, the test methods used in the embodiments of the present invention are all conventional methods; the materials, reagents, etc. used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0055] Example 1

[0056] Diacerein solution (0.1 mg / ml) was mixed with GELMA hydrogel preparatory solution to obtain GELMA-DIA gel, which was implanted subcutaneously in C57 mice. The material was removed at 14 days and photographed to observe the capsule formation. Figure 1 As shown in the figure, the effect of the implant containing diacerein (Dia) material (14d). After 14 days, the hydrogel containing diacerein did not form an obvious capsule structure, while the blank control group had a complete capsule. This shows that the hydrogel containing diacerein can inhibit the formation of the capsule.

[0057] like Figure 2 The figure shows the wound regeneration and healing speed comparison of the diacerein group. The wound healing speed of mice injected subcutaneously with diacerein hydrogel was significantly faster than that of the control group hydrogel, proving that diacerein can promote wound healing.

[0058] like Figure 3 The figure shows the comparison of hair follicle regeneration in the wound of the diacerein group. In the figure, after the wound of the mouse subcutaneously injected with diacerein hydrogel healed, the regenerated hair follicle structure can be seen in the center of the scar, indicating that diacerein can promote the regeneration of hair follicles and appendages in the process of local wound healing.

[0059] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. An application of diacerein and its derivatives in the preparation of a medicament for inhibiting fibrosis, characterized in that: Described diacerein and its derivatives have the following general structural formula: in: R1 is a straight or branched alkyl group of 1 to 6 carbon atoms; R2 is a straight or branched alkyl group of 1 to 6 carbon atoms; R3 is hydrogen or a straight or branched chain alkyl group of 1 to 6 carbon atoms; R1, R2 and R3 are the same or different; The fibrosis is fibrosis induced by biomaterials.

2. The use according to claim 1, characterized in that: R1 is methyl, R2 is methyl, and R3 is hydrogen.

3. The use according to claim 1, characterized in that: The drug is in the form of oral capsules, intravenous injections, external ointments or sprays; The dosage of the drug is 0-100 mg / ml.

4. An application of diacerein and its derivatives in the preparation of a medicament for promoting local tissue regeneration, characterized in that: Described diacerein and its derivatives have the following general structural formula: in: R1 is a straight or branched alkyl group of 1 to 6 carbon atoms; R2 is a straight or branched alkyl group of 1 to 6 carbon atoms; R3 is hydrogen or a straight or branched chain alkyl group of 1 to 6 carbon atoms; R1, R2 and R3 are the same or different; The local tissue includes hair follicles and appendages in the process of wound healing.

5. The use according to claim 4, characterized in that: R1 is methyl, R2 is methyl, and R3 is hydrogen.

6. The use according to claim 4, characterized in that: The drug is in the form of oral capsules, intravenous injections, external ointments or sprays; The dosage of the drug is 0-100 mg / ml.

7. An application of diacerein and its derivatives in the preparation of a medicament for inhibiting fibrosis and promoting local tissue regeneration, characterized in that: Described diacerein and its derivatives have the following general structural formula: in: R1 is a straight or branched alkyl group of 1 to 6 carbon atoms; R2 is a straight or branched alkyl group of 1 to 6 carbon atoms; R3 is hydrogen or a straight or branched chain alkyl group of 1 to 6 carbon atoms; R1, R2 and R3 are the same or different; The fibrosis is fibrosis induced by biomaterials; The local tissue includes hair follicles and appendages in the process of wound healing.

8. The use according to claim 7, characterized in that: R1 is methyl, R2 is methyl, and R3 is hydrogen.

9. The use according to claim 7, characterized in that: The drug is in the form of oral capsules, intravenous injections, external ointments or sprays; The dosage of the drug is 0-100 mg / ml.

10. Use of diacerein and its derivatives in the preparation of medicines, comprising the use according to any one of claims 1 to 9, characterized in that: The drug includes pharmaceutically acceptable carriers and excipients; The drug further comprises any one or more of an absorption promoter, a surfactant or a synergist; The drug is physically blended with the biomaterial, or bound by chemical cross-linking.

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