Application of adrenosterone 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 adrenosterone 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 the adrenosterone and the derivative thereof, fibrosis induced by biological materials, 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 present invention belongs to the field of pharmaceutical technology, and particularly relates to the use of adrenosterone and its derivatives in the preparation of drugs for inhibiting fibrosis and promoting local tissue regeneration. Background Art

[0002] As a foreign body, a biomaterial may trigger acute and chronic inflammation in the body. The occurrence of acute inflammation may lead to implant failure, while chronic inflammation may affect the characteristics of the regenerated tissue. Therefore, it is necessary to control the abnormal reaction caused by the implantation of biomaterials. However, a moderate immune response is crucial for normal tissue repair. The broad-spectrum immunosuppressive drugs used in the past have also affected the regeneration process while suppressing the inflammatory response. Therefore, there is an urgent need to develop drugs with selective immunomodulatory functions to inhibit the biomaterial-related inflammatory response and promote the regeneration of local tissues. Summary of the Invention

[0003] To solve the deficiencies of the prior art, the present invention provides the use of adrenosterone and its derivatives in the preparation of drugs for inhibiting fibrosis and promoting local tissue regeneration.

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

[0005] The use of an adrenosterone and its derivatives in the preparation of a drug for inhibiting fibrosis, wherein the adrenosterone and its derivatives have the following general structural formula:

[0006]

[0007] Wherein:

[0008] R1 is a straight-chain or branched-chain alkyl group with 1 to 6 carbons, or is hydrogen;

[0009] R2 is a straight-chain or branched-chain alkyl group with 1 to 6 carbons, or is hydrogen;

[0010] R1 and R2 are the same or different;

[0011] The fibrosis is biomaterial-induced fibrosis.

[0012] The inventors have found that adrenosterone and its derivatives can resist biomaterial-induced fibrosis, the degree of immune cell infiltration, and tissue calcification, and exhibit resistance to acute or chronic inflammation caused by biomaterials.

[0013] Preferably, R1 is hydrogen and R2 is hydrogen, that is, adrenosterone, and the structural formula is as follows:

[0014]

[0015] Specifically, the dosage form of the drug is an oral capsule, an intravenous injection, an external application ointment or a spray.

[0016] Specifically, the dosage of the drug is 1 to 150 mg / ml.

[0017] The present invention also provides an application of adrenosterone and its derivatives in the preparation of a drug for promoting local tissue regeneration, and the adrenosterone and its derivatives have the following general structural formula:

[0018]

[0019] Wherein:

[0020] R1 is a straight-chain or branched-chain alkyl group with 1 to 6 carbon atoms, or is hydrogen;

[0021] R2 is a straight-chain or branched-chain alkyl group with 1 to 6 carbon atoms, or is hydrogen;

[0022] R1 and R2 are the same or different;

[0023] The local tissue includes hair follicles and appendages during the wound healing process.

[0024] The inventors found that adrenosterone and its derivatives can improve the wound regeneration and healing speed and promote local tissue regeneration.

[0025] Preferably, R1 is hydrogen and R2 is hydrogen, that is, adrenosterone.

[0026] Specifically, the dosage form of the drug is an oral capsule, an intravenous injection, an external application ointment or a spray.

[0027] Specifically, the dosage of the drug is 1 to 150 mg / ml.

[0028] The present invention also provides an application of adrenosterone and its derivatives in the preparation of a drug for inhibiting fibrosis and promoting local tissue regeneration, and the adrenosterone and its derivatives have the following general structural formula:

[0029]

[0030] Wherein:

[0031] R1 is a straight-chain or branched-chain alkyl group with 1 to 6 carbon atoms, or is hydrogen;

[0032] R2 is a straight-chain or branched-chain alkyl group with 1 to 6 carbon atoms, or is hydrogen;

[0033] R1 and R2 are the same or different;

[0034] The fibrosis is biomaterial-induced fibrosis;

[0035] The local tissue includes hair follicles and appendages during the wound healing process.

[0036] The inventors found that adrenosterone and its derivatives can not only resist biomaterial-induced fibrosis, the degree of immune cell infiltration, and tissue calcification, but also improve the wound regeneration and healing speed, and simultaneously achieve the effects of anti-fibrosis and promoting local tissue regeneration.

[0037] Preferably, R1 is hydrogen and R2 is hydrogen, which is adrenosterone.

[0038] Specifically, the dosage form of the drug is an oral capsule, an intravenous injection, an external application ointment, or a spray.

[0039] Specifically, the dosage of the drug is 1-150 mg / ml.

[0040] Specifically, the drug includes a pharmaceutically acceptable carrier and excipients.

[0041] Furthermore, the drug further includes any one or more of an absorption enhancer, a surfactant, or a synergist.

[0042] Furthermore, the drug is physically blended with a biomaterial or delivered by drug loading methods such as chemical cross-linking binding, etc., to provide a continuous or short-term therapeutic effect, and the effect of inhibiting the foreign body reaction and promoting regeneration is achieved by combining with the material.

[0043] The beneficial effects of the present invention are as follows:

[0044] The active ingredients involved in the present invention not only include adrenosterone, but also include derivatives having similar functions or structures to adrenosterone;

[0045] 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 adrenosterone had a weaker inflammatory reaction, a significantly reduced degree of fibrosis, and obvious signs of tissue regeneration;

[0046] By using the method of the present invention, the biomaterial containing adrenosterone has a lower capsule thickness, a reduced inflammatory level, and more obvious signs of tissue regeneration.

[0047] The beneficial effects of the present invention are as follows:

[0048] 1) Selecting adrenosterone can resist biomaterial-induced fibrosis, the degree of immune cell infiltration, and tissue calcification, and exhibit anti-biological material-induced acute or chronic inflammation;

[0049] 2) Selecting adrenosterone, with a neutral pH value, does not affect the local pH and physiological characteristics of biological tissues, has a more stable effect, and is more likely to achieve the expected effect;

[0050] 3) Adrenosterone, whose metabolite in the body is a physiological product, is safer and conforms to the normal physiological functions of the body. Description of the Drawings

[0051] Figure 1 It is a control chart of the effect of the implant containing adrenosterone material.

[0052] Figure 2 It is a control chart of the wound regeneration and healing speed of the adrenosterone group.

[0053] Figure 3 It is a control chart of the wound hair follicle regeneration of the adrenosterone group. Detailed Embodiments

[0054] 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.

[0055] Unless otherwise specified, the test methods used in the embodiments of the present invention are all conventional methods; the materials, reagents, etc. used, unless otherwise specified, are reagents and materials that can be obtained from commercial channels.

[0056] Example 1

[0057] Mix the adrenosterone solution with the GELMA hydrogel preparation solution to obtain a gel containing GELMA-ADR (adrenosterone 1 mg / ml), implant it subcutaneously in C57 mice, take out the material at 14 d, and take samples and photographs to observe the formation of the capsule. The results are as Figure 1 shown. It is a control chart of the effect of the implant containing adrenosterone (Adr) material (1 m). The left side in the figure is the control group (Control), and the right side is the experimental group (Adr). After 14 days, the hydrogel containing adrenosterone did not form an obvious capsule structure, while a complete capsule appeared in the blank control group. This indicates that the hydrogel of adrenosterone at the above dose can inhibit the formation of the capsule. After one month, the control group could not grow hair, while the experimental group grew hair.

[0058] As Figure 2 shown, it is a control chart of the wound regeneration and healing speed of the adrenosterone group (staining method). The left side in the figure is the control group (DMSO), and the right side is the experimental group (Adr). The wound healing speed of the mice subcutaneously injected with the hydrogel containing adrenosterone on the right side in the figure is significantly faster than that of the control group DMSO, proving that adrenosterone can promote wound healing.

[0059] As Figure 3As shown, it is a control diagram of wound hair follicle regeneration in the adrenal steroid group. On the left side in the figure is the control group, and on the right side is the experimental group. After the wound of the mouse subcutaneously injected with the hydrogel containing adrenal steroid healed, regenerated hair follicle structures can be seen in the center of the scar, indicating that adrenal steroid can promote the regeneration of hair follicles and appendages during the local wound healing process.

[0060] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

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

2. The use according to claim 1, characterized in that: R1 is hydrogen, and R2 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 1 to 150 mg / ml.

4. Use of adrenosterone and its derivatives in the preparation of a drug for promoting local tissue regeneration, characterized in that: The adrenosterone and its derivatives have the following general structural formula: in: R1 is a straight or branched chain alkyl group of 1 to 6 carbon atoms, or hydrogen; R2 is a straight or branched chain alkyl group of 1 to 6 carbon atoms, or hydrogen; R1 and R2 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 hydrogen, and R2 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 1 to 150 mg / ml.

7. Use of adrenosterone and its derivatives in the preparation of a drug for inhibiting fibrosis and promoting local tissue regeneration, characterized in that: The adrenosterone and its derivatives have the following general structural formula: in: R1 is a straight or branched chain alkyl group of 1 to 6 carbon atoms, or hydrogen; R2 is a straight or branched chain alkyl group of 1 to 6 carbon atoms, or hydrogen; R1 and R2 are the same or different; 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 hydrogen, and R2 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 1 to 150 mg / ml.

10. Use of adrenosteroid 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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