A pharmaceutical molecule for inhibiting collagen fiber formation and use thereof

Abstract

This invention relates to a drug molecule that inhibits collagen fiber formation and its application. The drug molecule comprises a hydrophilic unit, a lysyl oxidase inhibitory unit, a matrix metalloproteinase 2 (MMP2) responsive peptide, a collagen self-assembly interfering peptide, and a hydrophobic unit connected in sequence. The drug molecule contains two main active ingredients: a lysyl oxidase inhibitory unit that inhibits lysyl oxidase activity during collagen cross-linking, and a collagen self-assembly interfering peptide that inhibits collagen self-assembly. These two components can inhibit the covalent cross-linking process of collagen from multiple perspectives, reducing collagen fiber formation. Simultaneously, the MMP2 responsive peptide in the drug molecule responds to MMP2, causing the drug molecule to disintegrate and releasing the two main active ingredients. This inhibits excessive collagen deposition at wound sites and promotes collagen remodeling at skin wound sites towards characteristics closer to normal skin collagen.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, specifically to a drug molecule that inhibits collagen fiber formation and its application. Background Technology

[0002] Skin scars are a general term for the changes in appearance and histopathology of normal skin tissue caused by various traumas. They are a common fibrotic disease. After scars form, they affect the patient's appearance and are accompanied by itching and pain. Moreover, the resulting contractures can lead to varying degrees of functional impairment, such as tendon contractures, joint dislocations, motor dysfunction, and occupational psychological disorders, which reduce the patient's quality of life and bring a heavy economic and psychological burden to the later treatment.

[0003] During the formation of skin scars, disruption of collagen homeostasis leads to excessive deposition of type I collagen, which is the main cause of scar thickening and hardening. Therefore, developing effective inhibition strategies targeting type I collagen deposition is of great significance for reducing scar formation, shrinking scar area, decreasing scar thickness, and improving scar texture.

[0004] CN114286816A discloses a difluorohaloallylamine sulfone derivative inhibitor of lysyl oxidase, which can inhibit the activity of lysyl oxidase and can be used to treat fibrosis, cancer and / or scar formation.

[0005] However, existing drugs for treating skin scars rely on a single inhibitor, which cannot adequately inhibit collagen cross-linking and thus cannot achieve the best anti-scarring effect.

[0006] Therefore, developing a drug molecule that can inhibit collagen fiber formation from multiple aspects, thereby improving the efficiency of collagen deposition inhibition and anti-scarring effect, has become an urgent technical problem to be solved. Summary of the Invention

[0007] To address the shortcomings of existing technologies, the present invention aims to provide a drug molecule that inhibits collagen fiber formation and its application. This drug molecule can inhibit both the covalent cross-linking process of collagen and the collagen self-assembly process prior to covalent cross-linking, thereby improving the efficiency of collagen deposition inhibition and promoting scarless wound healing.

[0008] To achieve this objective, the present invention adopts the following technical solution:

[0009] In a first aspect, the present invention provides a drug molecule that inhibits the formation of collagen fibers, the drug molecule comprising, in sequence, a hydrophilic unit, a lysine oxidase inhibitory unit (LOX inhibitory unit), a matrix metalloproteinase 2 responsive peptide (MMP2 responsive peptide), a collagen self-assembly interfering peptide, a matrix metalloproteinase 2 responsive peptide (MMP2 responsive peptide), and a hydrophobic unit.

[0010] During collagen fiber assembly, covalent cross-linking promotes the transformation of soluble monomeric collagen molecules into stable, insoluble collagen fibers, playing a crucial role in collagen deposition. This covalent cross-linking is primarily driven by lysyl oxidase, making lysyl oxidase an effective target for intervening in collagen assembly. Collagen self-assembly occurs prior to covalent cross-linking, establishing a regular, periodic arrangement of collagen molecules. This self-assembly forms the basis for subsequent covalent cross-linking, and intervening in collagen self-assembly inhibits various subsequent cross-linking mechanisms.

[0011] Based on this, the present invention develops a drug molecule that inhibits the formation of collagen fibers, which contains two main active ingredients: a lysyl oxidase inhibitory unit (LOX inhibitory unit) that can inhibit the activity of lysyl oxidase (LOX) during collagen cross-linking and a collagen self-assembly interfering peptide that can inhibit collagen self-assembly. This molecule can inhibit the process of collagen covalent cross-linking in multiple ways and reduce the formation of collagen fibers.

[0012] Meanwhile, the drug molecule of this invention contains a matrix metalloproteinase 2 responsive peptide (MMP2 responsive peptide). Matrix metalloproteinase 2 (MMP2) is highly expressed during tissue repair and is the initiator of matrix remodeling. During matrix remodeling, the MMP2 responsive peptide in the drug molecule of this invention can respond to MMP2, thereby causing the drug molecule to disintegrate and release two active ingredients: a lysyl oxidase inhibitory unit (LOX inhibitory unit) and a collagen interfering peptide. This achieves a more comprehensive inhibition of collagen cross-linking and collagen formation, reducing the number of mature collagen fibers generated and weakening their anti-enzymatic ability. It inhibits excessive collagen deposition at the wound site and promotes collagen remodeling at the skin wound site towards characteristics closer to normal skin collagen.

[0013] Preferably, the amino acid sequence of the collagen self-assembly interfering peptide includes SEQ ID NO:1.

[0014] Preferably, the amino acid sequence of the matrix metalloproteinase 2 responsive peptide includes SEQ ID NO:2.

[0015] The specific sequence of SEQ ID NO:1 is GGGYDFGYD, and the specific sequence of SEQ ID NO:2 is PLGIAG.

[0016] Preferably, the lysyl oxidase inhibitory unit comprises a copper ion chelating agent modified with an amino acid residue, wherein the amino acid is selected from lysine or cysteine.

[0017] Preferably, the copper ion chelating agent comprises 1,4,7-triazacyclononane-1,4,7-triacetic acid.

[0018] This invention creatively discovers that 1,4,7-triazacyclononane-1,4,7-triacetic acid can effectively inhibit the activity of LOX and synergistically enhance the inhibition efficiency of collagen deposition with collagen self-assembly interfering peptides.

[0019] Preferably, the hydrophilic unit comprises methoxy-terminated polyethylene glycol.

[0020] Preferably, the number average molecular weight of the polyethylene glycol is 200 to 2000.

[0021] Among them, the specific point values ​​in the range of 200 to 2000 can be selected as 200, 400, 600, 800, 1000, 1200, 1400, 1600, 1800, 2000, etc.

[0022] Preferably, the hydrophobic unit comprises an alkyl chain having 10 to 25 carbon atoms modified with amino acid residues, wherein the amino acid is selected from lysine or cysteine.

[0023] Among them, the specific point values ​​in the range of 10 to 25 can be selected as 10, 12, 14, 16, 18, 20, 22, 25, etc.

[0024] Hydrophilic and hydrophobic units provide hydrophilicity and hydrophobicity to drug molecules, which facilitates the self-assembly of drug molecules into stable micelle structures under specific conditions, thereby improving the solubility, stability and bioavailability of drug molecules.

[0025] Preferably, the drug molecule has a structure as shown in Formula I.

[0026]

[0027] Formula I

[0028] The structural diagram of the drug molecule is shown below. Figure 1 As shown.

[0029] In a second aspect, the present invention provides nanoparticles that inhibit the formation of collagen fibers, the nanoparticles being formed by the self-assembly of drug molecules that inhibit the formation of collagen fibers as described in the first aspect in a solvent.

[0030] Preferably, the nanoparticles have a particle size of 80~150 nm.

[0031] The specific point values ​​in the 80~150 nm range can be selected from 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, etc.

[0032] Preferably, the solvent includes phosphate buffer.

[0033] In this invention, the nanoparticles formed by the self-assembly of drug molecules that inhibit collagen fiber formation have uniform particle size and stable structure. When the nanoparticles are co-incubated with MMP2, the MMP2-responsive peptides in the nanoparticles respond to MMP2, causing the nanoparticles to disintegrate and release the active substance.

[0034] Thirdly, the present invention provides the application of a drug molecule that inhibits collagen fiber formation as described in the first aspect or nanoparticles that inhibit collagen fiber formation as described in the second aspect in the preparation of scar removal drugs.

[0035] Fourthly, the present invention provides a drug-loaded gel that inhibits the formation of collagen fibers, wherein the raw materials for preparing the drug-loaded gel include modified gelatin and the nanoparticles for inhibiting the formation of collagen fibers described in the second aspect.

[0036] The drug-loaded gel constructed in this invention is suitable for skin wound repair applications. The moist healing environment provided by the gel can promote wound closure, and the nanoparticles can interfere with the formation of collagen fibers and inhibit excessive collagen deposition at the wound site.

[0037] Preferably, the modified gelatin includes methacrylated gelatin;

[0038] Preferably, the mass ratio of the modified gelatin to the nanoparticles that inhibit collagen fiber formation is (100~150):1.

[0039] Preferably, the solid content of the drug-loaded gel is 1-5%.

[0040] Among them, the specific point values ​​in the range of 100 to 150 can be 100, 110, 120, 130, 140, 150, etc., and the specific point values ​​in the range of 1 to 5% can be 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, etc.

[0041] When the modified gelatin and the nanoparticles that inhibit the formation of collagen fibers meet the above-mentioned specific ratio, the loading capacity of the nanoparticles can be increased while ensuring the gel properties.

[0042] Fifthly, the present invention provides a method for preparing a drug-loaded gel that inhibits collagen fiber formation as described in the fourth aspect, the method comprising the following steps:

[0043] Modified gelatin, collagen fiber-inhibiting nanoparticles, and a photoinitiator are mixed in a solvent and subjected to a cross-linking reaction under light to form the drug-loaded gel that inhibits collagen fiber formation.

[0044] Preferably, the photoinitiator comprises 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone.

[0045] Preferably, the wavelength of the illumination is 350~380 nm, and the power density is 50~100 mW·cm. −2 .

[0046] The specific point values ​​within the 350–380 nm range can be selected from 350 nm, 360 nm, 370 nm, 380 nm, etc., and the range is 50–100 mW·cm. −2 The specific point value can be selected as 50 mW·cm. −2 60 mW·cm −2 70 mW·cm −2 80 mW·cm −2 90 mW·cm −2 100 mW·cm −2 wait.

[0047] Preferably, the crosslinking reaction is carried out at a temperature of 15-40°C for a time of 10-60 min.

[0048] Among them, the specific point values ​​in the 15~40℃ range can be selected as 15℃, 20℃, 25℃, 30℃, 35℃, 40℃, etc., and the specific point values ​​in the 10~60min range can be selected as 10 min, 20 min, 30 min, 40 min, 50 min, 60 min, etc.

[0049] Preferably, the method for preparing the methacrylated gelatin includes the following steps:

[0050] Gelatin was dissolved in a phosphate buffer solution, and then reacted with methacrylamide. After the reaction was completed, phosphate buffer was added to terminate the reaction, resulting in methacrylated gelatin.

[0051] Preferably, the mixing and dissolving temperature is 40~70℃ and the time is 2~30min.

[0052] Preferably, the temperature for the reaction with methacrylamide is 40~70℃ and the time is 1~5h.

[0053] Among them, the specific point values ​​in the 40~70℃ range can be 40℃, 45℃, 50℃, 55℃, 60℃, 65℃, 70℃, etc.; the specific point values ​​in the 2~30min range can be 2min, 5min, 10min, 15min, 20min, 25min, 30min, etc.; and the specific point values ​​in the 1~5h range can be 1h, 2h, 3h, 4h, 5h, etc.

[0054] The numerical range described in this invention includes not only the point values ​​listed above, but also any point values ​​within the numerical ranges not listed above. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific point values ​​included in the range.

[0055] Compared with the prior art, the present invention has the following beneficial effects:

[0056] This invention develops a drug molecule that inhibits collagen fiber formation, comprising two main active ingredients: a lysyl oxidase inhibitory unit that inhibits lysyl oxidase activity during collagen cross-linking and a collagen self-assembly interfering peptide that inhibits collagen self-assembly. This multi-faceted approach inhibits the covalent cross-linking process of collagen, reducing collagen fiber formation. Simultaneously, the MMP2-responsive peptide in the drug molecule responds to MMP2, causing the drug molecule to disintegrate and release the two main active ingredients. This inhibits excessive collagen deposition at wound sites and promotes collagen remodeling at skin wound sites towards characteristics closer to normal skin collagen. Attached Figure Description

[0057] Figure 1 This is a schematic diagram of the structure of a drug molecule that inhibits collagen fiber formation;

[0058] Figure 2 This is a flowchart illustrating the preparation of the drug-loaded gel that inhibits collagen fiber formation in Example 2;

[0059] Figure 3 This is a transmission electron microscope image of the nanoparticles that inhibit collagen fiber formation prepared in Example 1;

[0060] Figure 4 This is a photograph of the drug-loaded gel that inhibits collagen fiber formation prepared in Example 2;

[0061] Figure 5 This is a scanning electron microscope image of the drug-loaded gel that inhibits collagen fiber formation prepared in Example 2;

[0062] Figure 6 This is a test diagram of the rheological properties of drug-loaded gels with different solid contents in Example 3;

[0063] Figure 7 This is a test diagram showing the inhibitory effect of nanoparticles on collagen fibers in Test Example 1.

[0064] Figure 8 This is a visual representation of the wound changes in rabbits from different experimental groups in Test Example 2;

[0065] Figure 9 These are two-photon imaging images of scar tissue from different experimental groups of rabbits in Test Example 2. Detailed Implementation

[0066] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0067] Example 1

[0068] This embodiment provides nanoparticles that inhibit collagen fiber formation, which are prepared by the following method:

[0069] (1) Synthesize the drug molecule shown in Formula I by solid-phase synthesis. The drug molecule includes a hydrophilic unit, a lysine oxidase inhibitory unit, a matrix metalloproteinase 2 responsive peptide, a collagen self-assembly interfering peptide, a matrix metalloproteinase 2 responsive peptide and a hydrophobic unit connected in sequence.

[0070] The hydrophilic unit is methoxy polyethylene glycol 500 (mPEG). 500 The hydrophobic unit is an 18-carbon alkyl chain (C18) modified with lysine residues; the lysine oxidase inhibitory unit is 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) modified with lysine residues; the amino acid sequence of the collagen self-assembly interfering peptide is SEQ ID NO:1: GGGYDFGYD; and the amino acid sequence of the matrix metalloproteinase 2 responsive peptide (MMP2 responsive peptide) is SEQ ID NO:2: PLGIAG.

[0071] One end of the hydrophilic group: mPEG 500 The structure of the drug molecule prepared is shown in Formula I. The NOTA and MMP2 responsive peptides are linked by lysine residues in the lysine oxidase inhibitory unit. The middle part: the MMP2 responsive peptide, collagen self-assembly interfering peptide, and MMP2 responsive peptide are linked by amide bonds. The hydrophobic side: the MMP2 responsive peptide and C18 are linked by lysine residues in the hydrophobic unit.

[0072]

[0073] Formula I

[0074] In this drug molecule, mPEG 500 The introduction of C18 provides the drug molecule with amphiphilicity, and the critical micelle concentration (CMC) of the drug molecule was measured to be 2.17 µM.

[0075] (2) Preparation of nanoparticles: Select a concentration 50 times that of CMC as the assembly concentration, drop the drug molecules synthesized in step (1) into PBS, sonicate at 25°C for 10 min to start self-assembly, and obtain nanoparticles that inhibit the formation of collagen fibers (abbreviated as NRCIP).

[0076] Example 2

[0077] This embodiment provides a drug-loaded gel with a solid content of approximately 1.8%, which is prepared by the following method:

[0078] (1) Preparation of methacrylated gelatin: Dissolve 1 g of gelatin (purchased from VETEC) in 10 mL of sterile PBS and stir at 50 °C for 10 min to dissolve it. After dissolution, add 50 μL of methacrylamide (MA) dropwise and react at 50 °C in the dark for 3 h. Then add 40 mL of PBS to terminate the reaction. Dialyze the gelatin in deionized water using a 3.5 kD dialysis bag for 36 h to remove unreacted MA. After lyophilization, obtain white solid methacrylated gelatin (GelMA).

[0079] (2) Dissolve 50 mg of lyophilized GelMA in 2 mL of PBS solution containing 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone (Irgacure 2959, 1%, w / v), add 4 μL of NRCIP (1 mg / 10 μL) prepared in Example 1, and immediately expose the mixture to UV-LED light (365 nm UV, 75 mW·cm). −2 The reaction was carried out for 30 min to obtain a drug-loaded gel with a solid content of approximately 1.8% (abbreviated as GelMA@NRCIP). The preparation process of this drug-loaded gel is as follows: Figure 2 As shown.

[0080] Example 3

[0081] This embodiment provides a drug-loaded gel with a solid content of approximately 7.2%. The only difference between this embodiment and Example 2 is that 50 mg of lyophilized GelMA is replaced with 200 mg of lyophilized GelMA, while the remaining steps are the same as in Example 2.

[0082] Verification Example 1

[0083] This verification example characterizes the structure of the nanoparticles that inhibit collagen fiber formation prepared in Example 1.

[0084] The collagen fiber-inhibiting nanoparticles (NRCIP) prepared in Example 1 were dissolved in water three times, sonicated for 15 min, stained with uranium acetate, and their structure was observed under a transmission electron microscope (Hitachi, model HT7700). Figure 3 As shown, the NRCIP particles have a diameter of approximately 115 nm and are uniformly dispersed.

[0085] Verification Example 2

[0086] This verification example characterizes the structure of the drug-loaded gel with a solid content of 2.5% prepared in Example 2.

[0087] The actual image of the drug-loaded gel prepared in Example 2 is shown below. Figure 4 As shown, the drug-loaded gel has a uniform texture and is easy to apply.

[0088] The drug-loaded gel prepared in Example 2 was subjected to liquid nitrogen brittle fracture and freeze-drying, followed by gold sputtering. The structure of the drug-loaded gel was observed under a scanning electron microscope (Hitachi, model SU8220). The results are as follows: Figure 5 As shown, the prepared drug-loaded gel has a porous structure, which can absorb wound exudate, provide a moist healing environment, and is conducive to wound healing.

[0089] Verification Example 3

[0090] This validation example tests the rheological properties of the drug-loaded gels prepared in Examples 2 and 3.

[0091] The rheological properties of the drug-loaded gels with different solid contents obtained in Examples 2 and 3 were tested, and the results are as follows: Figure 6 As shown, the storage modulus and loss modulus of the drug-loaded gel with a solid content of 7.2% both increased to varying degrees, and the gel texture became hard, making it unsuitable for application.

[0092] Test Example 1

[0093] The inhibitory effect of NRCIP on collagen fiber formation was tested.

[0094] (1) Experimental grouping:

[0095] Control group: 50 µL of 3 µg / mL collagen solution was added to a quartz plate and allowed to initiate self-assembly of collagen at 37°C. After 1 hour of self-assembly, the number of fibers formed was observed using an atomic force microscope (Cypher VRS, Oxford Instruments).

[0096] NRCIP group: 50 μL of 100 μM NRCIP solution was mixed with 50 μL of 0.2 μg / mL MMP2 solution and reacted at 37℃ for 3 h to allow NRCIP to be enzymatically hydrolyzed. Then, 2 µL of the above solution was added to 100 µL of 3 µg / mL collagen solution. 50 µL of the collagen solution was placed on a quartz slide, and the collagen was allowed to self-assemble at 37℃. After 1 h of self-assembly, the number of fibers formed was observed using atomic force microscopy.

[0097] (2) Experimental results:

[0098] The results of comparing the inhibitory effects of adding NRCIP on collagen fiber production are as follows: Figure 7 As shown in the figure, the number of collagen fibers formed by collagen self-assembly in the NRCIP group was significantly reduced, proving that NRCIP can effectively inhibit collagen self-assembly.

[0099] Test Example 2

[0100] The effect of drug-loaded gel on promoting wound healing was tested.

[0101] (1) Construction of a wounded rabbit model: New Zealand white rabbits (adult, 2.5kg, purchased from Beijing Jinmuyang Experimental Animal Breeding Co., Ltd.) were anesthetized, and circular incisions with a diameter of 7 mm were made on both sides of the ventral side of the ear. The epidermis, dermis, and perichondrium of each wound were completely removed, while the cartilage was kept intact. Pressure was applied to stop bleeding. One day after the operation, antibiotics were injected to prevent infection. At the same time, routine disinfection of the wound was carried out daily for 1 to 5 days after the operation, and secretions were removed.

[0102] (2) Trial grouping: On the 6th day after surgery, the treatment group was covered with 100 µL of drug-loaded gel per wound and wrapped with gauze. The dressing was changed every other day until the 30th day after surgery. The control group was wrapped with gauze only from the 6th day after surgery, without covering with drug-loaded gel.

[0103] Visual representation of wound changes Figure 8 As shown, the wound in the treatment group showed significant healing on the 10th day after surgery, and the scar protrusion was significantly reduced compared to the control group 30 days after surgery.

[0104] (3) Scar tissue treatment efficacy test:

[0105] All New Zealand white rabbits died from overdose anesthesia after rapid injection of sodium pentobarbital into the marginal auricular vein on postoperative day 30. Hypertrophic scar tissue specimens were rapidly excised, with 0.3 cm of normal tissue preserved at the cut margin, extending to the cartilage. The excised scar tissue was fixed in 4% formaldehyde solution, routinely dehydrated, embedded in paraffin, and then examined for collagen composition under a two-photon microscope. The results are as follows: Figure 9 As shown. By Figure 9 It is evident that obvious and randomly arranged collagen fibers were observed in the control group, while the number of collagen fibers in the treatment group with the drug-loaded gel was less, indicating that the drug in the drug-loaded gel had been released, thereby intervening in the formation of collagen fibers and inhibiting excessive collagen deposition at the wound site.

[0106] The applicant declares that the technical solution of this invention is illustrated by the above embodiments, but this invention is not limited to the above embodiments, that is, it does not mean that this invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the products of this invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

[0107] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0108] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A drug molecule that inhibits collagen fiber formation, characterized in that, The drug molecule comprises a hydrophilic unit, a lysine oxidase inhibitory unit, a matrix metalloproteinase 2 responsive peptide, a collagen self-assembly interfering peptide, a matrix metalloproteinase 2 responsive peptide, and a hydrophobic unit connected in sequence. The drug molecule has a structure as shown in Formula I: Formula I.

2. A nanoparticle for inhibiting collagen fiber formation, characterized in that, The nanoparticles are formed by the self-assembly of the drug molecules that inhibit collagen fiber formation as described in claim 1 in a solvent.

3. The nanoparticles according to claim 2, characterized in that, The nanoparticles have a particle size of 80~150 nm.

4. The nanoparticles according to claim 2, characterized in that, The solvent includes phosphate buffer.

5. The use of a drug molecule that inhibits collagen fiber formation as described in claim 1 or nanoparticles that inhibit collagen fiber formation as described in claim 2 in the preparation of scar removal drugs.

6. A drug-loaded gel that inhibits collagen fiber formation, characterized in that, The raw materials for preparing the drug-loaded gel include modified gelatin and the nanoparticles for inhibiting collagen fiber formation as described in claim 2.

7. The drug-loaded gel according to claim 6, characterized in that, The modified gelatin includes methacrylated gelatin.

8. The drug-loaded gel according to claim 6, characterized in that, The mass ratio of the modified gelatin to the nanoparticles that inhibit the formation of collagen fibers is (100~150):

1.

9. The drug-loaded gel according to claim 6, characterized in that, The drug-loaded gel has a solid content of 1-5%.

10. A method for preparing a drug-loaded gel for inhibiting collagen fiber formation as described in claim 6, characterized in that, The preparation method includes the following steps: Modified gelatin, collagen fiber-inhibiting nanoparticles, and a photoinitiator are mixed in a solvent and subjected to a cross-linking reaction under light to form the drug-loaded gel that inhibits collagen fiber formation.

11. The preparation method according to claim 10, characterized in that, The photoinitiator includes 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone.

12. The preparation method according to claim 10, characterized in that, The wavelength of the illumination is 350~380 nm, and the power density is 50~100 mW·cm. −2 .

13. The preparation method according to claim 10, characterized in that, The cross-linking reaction is carried out at a temperature of 15~40℃ for a time of 10~60 min.

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