Bioactive gel for treating alopecia and preparation method and application thereof

Abstract

The invention discloses bioactive gel for treating alopecia as well as a preparation method and application of the bioactive gel. The bioactive gel for treating alopecia is prepared from the following raw materials: a therapeutic agent, lipidosome, oxidized dextran and carboxymethyl chitosan quaternary ammonium salt. In the preparation raw materials of the bioactive gel, the mass fraction of the therapeutic agent is 1-3 wt%, the mass fraction of the oxidized dextran is 1-3 wt%, the mass fraction of the carboxymethyl chitosan quaternary ammonium salt is 4-6 wt%, and the ratio of the therapeutic agent to the lipidosome is 1: (5-15). The bioactive gel for treating alopecia is prepared by taking the safe and non-toxic liposome which easily penetrates through the skin cuticle as a carrier and by virtue of the advantages of good biocompatibility, adhesion and the like of the gel, and the gel has good biocompatibility and adhesion in vitro and high transdermal rate in vivo, and can be used for treating alopecia. The defects that the minoxidil tincture and foaming agent in the prior art are easy to flow and low in transdermal rate are overcome.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, and in particular to a bioactive gel for treating hair loss, and a preparation method and application thereof. Background Art

[0002] In recent years, with the increase of work and life pressure, hair loss has become more and more common. The mental stress it brings has had a serious negative impact on people's lives, so the demand for hair loss treatment has soared. From the perspective of clinical diagnosis, hair loss is mainly divided into alopecia areata, androgenic alopecia (AGA), drug-induced anagen effluvium, etc. Among them, androgenic alopecia (AGA) is the most common type of hair loss. Minoxidil (MXD) is an adenosinetriphosphate (ATP)-sensitive potassium ion channel opener and has been approved by the US FDA for the treatment of hair loss. Currently, the commonly used minoxidil products on the market are tinctures and foams, but tinctures and foams have the disadvantages of easy flow and low transdermal penetration. Summary of the invention

[0003] To overcome the above disadvantages, the present invention provides a bioactive gel for treating hair loss, which has good adhesion and high skin penetration rate.

[0004] In order to achieve the above purpose, the technical solution adopted by the present invention is: a bioactive gel for treating hair loss, wherein the raw materials for preparing the bioactive gel include: a therapeutic agent, liposomes, oxidized dextran, and carboxymethyl chitosan quaternary ammonium salt.

[0005] Furthermore, in the raw materials for preparing the bioactive gel, the mass fraction of the therapeutic agent is 1-3wt%, the mass fraction of oxidized dextran is 1-3wt%, the mass fraction of carboxymethyl chitosan quaternary ammonium salt is 4-6wt%, and the weight ratio of the therapeutic agent to the liposome is 1:5-15. Exemplarily, the mass fraction of the therapeutic agent is 1wt%,

[0006] 1.5wt%, 2wt%, 2.5wt%, 3wt%, the mass fraction of oxidized dextran is 1wt%, 1.5wt%, 2wt%, 2.5wt%, 3wt%, the mass fraction of carboxymethyl chitosan quaternary ammonium salt is 4wt%, 4.5wt%, 5wt%, 5.5wt%, 6wt%, and the weight ratio of therapeutic agent and liposome is 1:5, 1:8, 1:10, 1:12, 1:15.

[0007] Further, the liposome includes soybean lecithin and cholesterol, and the weight ratio of soybean lecithin to cholesterol is 1:1 to 3. Exemplarily, the weight ratio of soybean lecithin to cholesterol is 1:1, 1:2, 1:3.

[0008] Further, the therapeutic agent is minoxidil.

[0009] Another aspect of the present invention provides a method for preparing the bioactive gel as described above, comprising the following steps:

[0010] S1, synthetic minoxidil-loaded liposomes;

[0011] S2. Adding minoxidil-loaded liposomes to the oxidized dextran solution and mixing the mixture, and then mixing the mixture with the carboxymethyl chitosan quaternary ammonium salt solution to obtain a bioactive gel.

[0012] Further, in S1, the steps of synthesizing minoxidil-loaded liposomes are:

[0013] S11, weighing soybean lecithin and cholesterol, dissolving them in an organic solvent, and removing the organic solvent to obtain liposomes, wherein the weight ratio of soybean lecithin to cholesterol is 1:1-3;

[0014] S12, dissolving minoxidil, and then mixing it with liposomes, wherein the weight ratio of minoxidil to liposomes is 1:5-15.

[0015] Further, in S2, the concentration of the oxidized dextran solution is 4-8wt%, the concentration of the carboxymethyl chitosan quaternary ammonium salt solution is 6-10wt%, and the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt solution is 1:1 to 2. Exemplarily, the concentration of the oxidized dextran solution is 4wt%, 5wt%, 6wt%, 7wt%, 8wt%, the concentration of the carboxymethyl chitosan quaternary ammonium salt is 6wt%, 7wt%, 8wt%, 9wt%, 10wt%, and the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt is 1:1, 1:1.5, 1:2.

[0016] Furthermore, in S2, the oxidized dextran is prepared by oxidizing dextran, and the carboxymethyl chitosan quaternary ammonium salt is prepared by grafting quaternary ammonium salt onto carboxymethyl chitosan.

[0017] Further, in S11, the organic solvent is a mixed solution of methanol and chloroform, wherein the volume ratio of methanol to chloroform is 1:2 to 4. Exemplarily, the volume ratio of methanol to chloroform is 1:2, 1:3, 1:4.

[0018] The present invention also provides the use of the bioactive gel or the preparation method described above in preparing a drug for treating hair loss.

[0019] The beneficial effects of the present invention are:

[0020] 1) The present invention uses liposomes that are easy to penetrate the stratum corneum of the skin and are safe and non-toxic as carriers, and takes advantage of the advantages of the gel such as good biocompatibility and adhesion to prepare a bioactive gel for treating hair loss. The gel has good biocompatibility and adhesion in vitro and a high transdermal rate in vivo, thus solving the shortcomings of the current minoxidil tincture and foam, such as easy flow and low transdermal rate.

[0021] 2) The bioactive gel provides the adhesion required for skin residence and sustained release to achieve a sustained therapeutic effect.

[0022] 3) The ODex-QCMC hydrogel prepared by the present invention has antibacterial properties, self-healing properties and injectability.

[0023] 4) The gel raw materials oxidized dextran and carboxymethyl chitosan quaternary ammonium salt used in the present invention are widely available, low in cost, simple in preparation process, and are expected to be industrially applied, and the product market demand is large. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The drawings constituting a part of this application are used to provide a further understanding of the present invention. The illustrative embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0026] Figure 1 is the TEM image of minoxidil-loaded liposomes;

[0027] Figure 2 This is the dynamic light scattering graph of minoxidil-loaded liposomes;

[0028] Figure 3 Schematic diagram of ODex-QCMC hydrogel formation;

[0029] Figure 4 is the SEM image of ODex-QCMC hydrogel;

[0030] Figure 5 Schematic diagram of hydrogel self-healing;

[0031] Figure 6 Schematic diagram of hydrogel injection;

[0032] Figure 7 This is a graph showing the relationship between time and release amount of the Lip@MXD-GEL gel drug prepared in Example 1. DETAILED DESCRIPTION

[0033] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below.

[0034] Except as shown in the operating examples or otherwise indicated, all numbers used in the specification and claims to indicate the amount of ingredients, physicochemical properties, etc. are understood to be adjusted by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters listed in the above specification and the attached claims are approximate values, and those skilled in the art can use the teachings disclosed herein to seek to obtain the desired properties and appropriately change these approximate values. The use of numerical ranges expressed as endpoints includes all numbers within the range and any range within the range, for example, 1 to 5 includes 1, 1.1, 1.3, 1.5, 2, 2.75, 3, 3.80, 4 and 5, etc.

[0035] The applicant has found that the commonly used minoxidil products on the market are tinctures and foams, but the tinctures and foams have the disadvantages of being easy to flow and having low skin penetration rate. Therefore, one embodiment of the present invention provides a bioactive gel for treating hair loss, which has good biocompatibility and adhesion and has a high skin penetration rate in vivo. The preparation method thereof comprises the following steps:

[0036] S1, synthetic minoxidil-loaded liposomes;

[0037] In a round-bottom flask, weigh soybean lecithin and cholesterol and dissolve them in an organic solvent, the weight ratio of soybean lecithin to cholesterol is 1:1-3, the organic solvent is a mixed solution of methanol and chloroform, wherein the volume ratio of methanol to chloroform is 1:2-4, and the organic solvent is removed by rotary evaporation to form a liposome film (lipid membrane) on the wall of the round-bottom flask. Then, minoxidil is dissolved in a mixed solution of deionized water and anhydrous ethanol (water-to-alcohol ratio is 1:1), poured into a round-bottom flask, and rotary evaporation is continued to obtain a white emulsion (minoxidil-loaded liposome solution Lip@MXD), which is ultrasonically reduced in size for 20 minutes. The weight ratio of minoxidil to liposome is 1:5-15.

[0038] S2. Adding minoxidil-loaded liposomes to the oxidized dextran solution and mixing the mixture, and then mixing the mixture with carboxymethyl chitosan quaternary ammonium salt to obtain a bioactive gel.

[0039] The oxidized dextran is prepared by oxidizing dextran, and the concentration of the oxidized dextran solution is 4-8wt%; the carboxymethyl chitosan quaternary ammonium salt is prepared by grafting quaternary ammonium salt onto carboxymethyl chitosan, and the concentration of the carboxymethyl chitosan quaternary ammonium salt solution is 6-10wt%; the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt is 1:1-2.

[0040] Example

[0041] The following examples describe the disclosure of the present invention in more detail, and these examples are intended for illustrative purposes only, as various modifications and variations within the scope of the disclosure of the present invention will be apparent to those skilled in the art. Unless otherwise stated, all parts, percentages, and ratios reported in the following examples are by weight, and all reagents used in the examples are commercially available or synthesized according to conventional methods and can be used directly without further processing, and the instruments used in the examples are commercially available.

[0042] Example 1

[0043] S1, synthetic minoxidil-loaded liposomes;

[0044] In a round-bottom flask, weigh soybean lecithin and cholesterol and dissolve them in an organic solvent, the weight ratio of soybean lecithin to cholesterol is 1:2, the organic solvent is a mixed solution of methanol and chloroform, wherein the volume ratio of methanol to chloroform is 1:3, and the organic solvent is removed by rotary evaporation to form a liposome film (lipid membrane) on the wall of the round-bottom flask. Then, minoxidil is dissolved in a mixed solution of deionized water and anhydrous ethanol (water-to-alcohol ratio is 1:1), poured into a round-bottom flask, and rotary evaporation is continued to obtain a minoxidil-loaded liposome solution Lip@MXD (white emulsion) with a minoxidil mass fraction of 8wt%, and the size is reduced by ultrasonication for 20min. The weight ratio of minoxidil to liposome is 1:10.

[0045] S2. Add the minoxidil-loaded liposome solution Lip@MXD to the oxidized dextran solution and mix them, and then mix them with the carboxymethyl chitosan quaternary ammonium salt solution to obtain a bioactive gel.

[0046] Oxidized dextran is prepared by oxidizing dextran, and the concentration of the oxidized dextran (ODex) solution is 6wt%; carboxymethyl chitosan quaternary ammonium salt (QCMC) is prepared by grafting quaternary ammonium salt to carboxymethyl chitosan, and the concentration of carboxymethyl chitosan quaternary ammonium salt is 8wt%, and the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt solution is 1:2. The volume ratio of the white emulsion to the oxidized dextran solution is 1:1.

[0047] In the preparation of raw materials, assuming that the volume of oxidized dextran solution is 1, the volume of carboxymethyl chitosan quaternary ammonium salt solution is 2, and the volume of minoxidil-loaded liposome solution is 1, the mass fraction of minoxidil (MXD) is calculated to be: (8wt%×1) / (1+2+1)=2wt%, the mass fraction of liposomes is: 2wt%*10=20wt%, the mass fraction of oxidized dextran (ODex) is: (6wt%×1) / (1+2+1)=1.5wt%, and the mass fraction of carboxymethyl chitosan quaternary ammonium salt (QCMC) is: (8wt%×2) / (1+2+1)=4wt%.

[0048] Example 2

[0049] S1, synthetic minoxidil-loaded liposomes;

[0050] In a round-bottom flask, weigh soybean lecithin and cholesterol and dissolve them in an organic solvent, the weight ratio of soybean lecithin to cholesterol is 1:1, the organic solvent is a mixed solution of methanol and chloroform, wherein the volume ratio of methanol to chloroform is 1:2, and the organic solvent is removed by rotary evaporation to form a liposome film (lipid membrane) on the wall of the round-bottom flask. Then, minoxidil is dissolved in a mixed solution of deionized water and anhydrous ethanol (water-to-alcohol ratio is 1:1), poured into a round-bottom flask, and rotary evaporation is continued to obtain a minoxidil-loaded liposome solution Lip@MXD (white emulsion) with a minoxidil mass fraction of 5wt%, and the size is reduced by ultrasonication for 20min. The weight ratio of minoxidil to liposome is 1:15.

[0051] S2. Add the minoxidil-loaded liposome solution Lip@MXD to the oxidized dextran solution and mix them, and then mix them with the carboxymethyl chitosan quaternary ammonium salt solution to obtain a bioactive gel.

[0052] Oxidized dextran is prepared by oxidizing dextran, and the concentration of the oxidized dextran (ODex) solution is 7wt%, and carboxymethyl chitosan quaternary ammonium salt (QCMC) is prepared by grafting quaternary ammonium salt onto carboxymethyl chitosan. The concentration of carboxymethyl chitosan quaternary ammonium salt is 10wt%, the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt solution is 1:1, and the volume ratio of the white emulsion to the oxidized dextran solution is 1:2.

[0053] In the preparation of raw materials, assuming that the volume of the oxidized dextran solution is 2, the volume of the carboxymethyl chitosan quaternary ammonium salt solution is 2, and the volume of the minoxidil-loaded liposome solution is 1, the mass fraction of minoxidil is calculated to be: (5wt%×1) / (2+2+1)=1wt%, the mass fraction of the liposome is: 1wt%*15=15wt%, the mass fraction of the oxidized dextran (ODex) is: (7wt%×2) / (2+2+1)=2.8wt%, and the mass fraction of the carboxymethyl chitosan quaternary ammonium salt (QCMC) is: (10wt%×2) / (2+2+1)=4wt%.

[0054] Example 3

[0055] S1, synthetic minoxidil-loaded liposomes;

[0056] In a round-bottom flask, weigh soybean lecithin and cholesterol and dissolve them in an organic solvent, the weight ratio of soybean lecithin to cholesterol is 1:3, the organic solvent is a mixed solution of methanol and chloroform, wherein the volume ratio of methanol to chloroform is 1:4, and the organic solvent is removed by rotary evaporation to form a liposome film (lipid membrane) on the wall of the round-bottom flask. Then, minoxidil is dissolved in a mixed solution of deionized water and anhydrous ethanol (water-to-alcohol ratio is 1:1), poured into a round-bottom flask, and rotary evaporation is continued to obtain a minoxidil-loaded liposome solution Lip@MXD (white emulsion) with a minoxidil mass fraction of 7.5wt%, and the size is reduced by ultrasonication for 20min. The weight ratio of minoxidil to liposome is 1:5.

[0057] S2. Add the minoxidil-loaded liposome solution Lip@MXD to the oxidized dextran solution and mix them, and then mix them with the carboxymethyl chitosan quaternary ammonium salt solution to obtain a bioactive gel.

[0058] Oxidized dextran is prepared by oxidizing dextran, and the concentration of the oxidized dextran (ODex) solution is 8wt%, and carboxymethyl chitosan quaternary ammonium salt (QCMC) is prepared by grafting quaternary ammonium salt onto carboxymethyl chitosan. The concentration of carboxymethyl chitosan quaternary ammonium salt is 10wt%, the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt solution is 1:2, and the volume ratio of the white emulsion to the oxidized dextran solution is 2:1.

[0059] In the preparation of raw materials, assuming that the volume of oxidized dextran solution is 1, the volume of carboxymethyl chitosan quaternary ammonium salt solution is 2, and the volume of minoxidil-loaded liposome solution is 2, the mass fraction of minoxidil is calculated as:

[0060] (7.5wt%×2) / (2+2+1)=3wt%, the mass fraction of liposomes is: 3wt%*5=15wt%, the mass fraction of oxidized dextran (ODex) is: (8wt%×1) / (2+2+1)=1.6wt%, the mass fraction of quaternary ammonium salt of carboxymethyl chitosan (QCMC) is: (10wt%×2) / (2+2+1)=4wt%.

[0061] Example 4

[0062] S1, synthetic minoxidil-loaded liposomes;

[0063] In a round-bottom flask, weigh soybean lecithin and cholesterol and dissolve them in an organic solvent, the weight ratio of soybean lecithin to cholesterol is 1:2, the organic solvent is a mixed solution of methanol and chloroform, wherein the volume ratio of methanol to chloroform is 1:3, and the organic solvent is removed by rotary evaporation to form a liposome film (lipid membrane) on the wall of the round-bottom flask. Then, minoxidil is dissolved in a mixed solution of deionized water and anhydrous ethanol (water-to-alcohol ratio is 1:1), poured into a round-bottom flask, and rotary evaporation is continued to obtain a minoxidil-loaded liposome solution Lip@MXD (white emulsion) with a minoxidil mass fraction of 8wt%, and the size is reduced by ultrasonication for 20min. The weight ratio of minoxidil to liposome is 1:10.

[0064] S2. Adding minoxidil-loaded liposomes to the oxidized dextran solution and mixing the mixture, and then mixing the mixture with carboxymethyl chitosan quaternary ammonium salt to obtain a bioactive gel.

[0065] Oxidized dextran is prepared by oxidizing dextran, and the concentration of the oxidized dextran (ODex) solution is 6wt%, and carboxymethyl chitosan quaternary ammonium salt (QCMC) is prepared by grafting quaternary ammonium salt to carboxymethyl chitosan. The concentration of carboxymethyl chitosan quaternary ammonium salt is 10wt%, and the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt is 1:2. The volume ratio of the white emulsion to the oxidized dextran solution is 1:2.

[0066] In the preparation of raw materials, assuming that the volume of oxidized dextran solution is 1, the volume of carboxymethyl chitosan quaternary ammonium salt is 2, and the volume of minoxidil-loaded liposome solution is 0.5, the mass fraction of minoxidil (MXD) is calculated to be: (8wt%×0.5) / (1+2+0.5)=1.1wt%, the mass fraction of liposome is: 1.1wt%*10=11wt%, the mass fraction of oxidized dextran (ODex) is: (6wt%×1) / (1+2+0.5)=1.7wt%, and the mass fraction of carboxymethyl chitosan quaternary ammonium salt (QCMC) is: (10wt%×2) / (1+2+0.5)=5.7wt%.

[0067] Comparative Example

[0068] Preparation of Minoxidil MXD Tincture: The preparation process is to dissolve minoxidil (4 mg) in a mixed solution of anhydrous ethanol and propylene glycol, heat it in a 40°C water bath to completely dissolve it. Pour the solution into a 10 mL volumetric flask, add distilled water to the mark, and dilute to obtain minoxidil tincture.

[0069] Test Example 1

[0070] The minoxidil-loaded liposomes prepared in step S1 of Example 1 were observed by transmission electron microscopy, see attached Figure 1 As shown, it can be observed that the minoxidil-loaded liposomes are round or oval, indicating that the minoxidil-loaded liposomes were successfully prepared.

[0071] Nanoparticle size analyzer was used to characterize the particle size, PDI and zeta potential of the minoxidil-loaded liposomes in Example 1. Figure 2 As shown, the dynamic light scattering (DLS) results of the minoxidil-loaded liposomes are: the average particle size is 197.7±1.026nm, which meets the size required for skin penetration, the polymer dispersibility index PDI is 0.239±0.008, and the zeta potential is -12.46±1.4mV. This shows that the prepared minoxidil-loaded liposomes are dispersed relatively evenly and have a negative potential.

[0072] Minoxidil encapsulation efficiency: Take 10mL of minoxidil-loaded liposome suspension and centrifuge at 10000r / min for 15min. Measure the absorbance of the supernatant with a UV spectrophotometer and calculate the drug content in the supernatant. From this, the encapsulation efficiency of minoxidil in the liposome can be calculated. The result is 77.58%, indicating that most of the drug is encapsulated in the liposome.

[0073] Test Example 2

[0074] The 6% oxidized dextran (ODex) solution and the 8% carboxymethyl chitosan quaternary ammonium salt (QCMC) solution in Example 1 were mixed at a volume ratio of 1:2 to obtain an ODex-QCMC hydrogel. Figure 3 As shown, Figure 3 Figure a shows the ungelled state. Figure 3 Figure b shows the gelation state. Figure 3 It can be seen that the oxidized dextran (ODex) solution and the quaternary ammonium carboxymethyl chitosan (QCMC) solution are used as raw materials to prepare the gel, which has fast gelation and good viscosity.

[0075] From the attached Figure 4 An obvious three-dimensional interconnected pore structure can be observed in the SEM image of ODex-QCMC hydrogel.

[0076] Test Example 3

[0077] Hydrogel self-healing property: see attached Figure 5 As described above, the complete hydrogel was cut into two halves ( Figure 5 The two halves of the hydrogel were then dyed red and blue ( Figure 5 b), and then put the two stained hydrogels together ( Figure 5 After a while, the boundary in the middle becomes blurred ( Figure 5 Figure d in the figure shows that the two hydrogels are cross-linked again, proving that the gel has self-healing properties.

[0078] Hydrogel injectability: The gel was first stained with red dye and then demonstrated by injection via a syringe. Figure 6 As shown, successful injection of the gel can be observed, proving that the gel is injectable.

[0079] Test Example 4

[0080] Antibacterial experiment: Escherichia coli and Staphylococcus aureus were used to conduct in vitro antibacterial experiments on the hydrogel, and the hydrogel was from the ODex-QCMC hydrogel prepared in Test Example 2. The qualitative antibacterial results showed that no bacteria grew in the area where the hydrogel contacted, proving that the material had a certain antibacterial effect. The quantitative antibacterial test more clearly proved the antibacterial rate of the material, and the antibacterial rate against Escherichia coli and Staphylococcus aureus was about 90%.

[0081] Test Example 3

[0082] In vitro drug release: Franz diffusion cell was used to study the release of MXD in hydrogel. In the experiment, the Lip@MXD-GEL gel prepared in Example 1 was placed on pig skin between the donor chamber and the receptor chamber of the Franz diffusion cell, with the epidermal side facing the donor chamber. The receptor chamber was filled with 0.05M phosphate buffer solution (PBS pH 7.4), stirred continuously and kept at a constant temperature of 37±0.5°C. The donor chamber was filled with the gel prepared in Example 1 or the minoxidil tincture prepared in the comparative example. At a predetermined time, 0.3mL of buffer solution was taken out from the receptor chamber, the MXD content was analyzed by ultraviolet spectrophotometer, and replaced with fresh buffer solution. The amount of MXD released at different time intervals was calculated.

[0083] The test results show that the release amount of the Lip@MXD-GEL gel drug prepared in Example 1 can reach more than 80% in 8 hours, and the release amount gradually increases within 8 hours, indicating that the drug is continuously released (the release amount of the gel drug over a period of time is shown in Figure 7 ), while the MXD tincture in the comparative example completely released the drug within 2 hours. This indicates that the hydrogel provided by the present application provides the adhesion required for skin residence and the sustained release effect to achieve a sustained therapeutic effect.

[0084] Test Example 4

[0085] Animal experiment: First, testosterone was injected into mice to prepare a hair loss mouse model, and the hair loss mice were randomly divided into 3 groups, 10 in each group, namely Lip@MXD-GEL, positive control group (MXD tincture prepared in the comparative example) and negative control group (normal saline). The above formulations were applied to the hair loss area of ​​the mice once a day until the hair could completely cover the flank skin. During this period, the hair growth of the mice was observed daily and photographed for record.

[0086] The results showed that new hair grew in the hair loss area of ​​mice treated with Lip@MXD-GEL and the positive control group, while no new hair grew in the saline group. Moreover, the flank skin of the mice in the Lip@MXD-GEL group was completely covered 30 days after treatment, and the new hair of the mice was denser and more numerous.

[0087] The above implementation modes are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the content of the present invention and implement it, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A bioactive gel for treating hair loss, characterized in that: The raw materials for preparing the bioactive gel include: therapeutic agent, liposome, oxidized dextran and carboxymethyl chitosan quaternary ammonium salt.

2. The bioactive gel according to claim 1, characterized in that In the raw materials for preparing the bioactive gel, the mass fraction of the therapeutic agent is 1-3wt%, the mass fraction of oxidized dextran is 1-3wt%, the mass fraction of carboxymethyl chitosan quaternary ammonium salt is 4-6wt%, and the weight ratio of the therapeutic agent to the liposome is 1:5-15.

3. The bioactive gel according to claim 1, characterized in that The liposome comprises soybean lecithin and cholesterol, and the ratio of soybean lecithin to cholesterol is 1:1-3 by weight.

4. The bioactive gel according to claim 1, characterized in that The therapeutic agent is minoxidil.

5. A method for preparing the bioactive gel according to any one of claims 1 to 4, characterized in that: The steps include: S1, synthetic minoxidil-loaded liposomes; S2. Adding minoxidil-loaded liposomes to the oxidized dextran solution and mixing the mixture, and then mixing the mixture with the carboxymethyl chitosan quaternary ammonium salt solution to obtain a bioactive gel.

6. The method for preparing the bioactive gel according to claim 5, characterized in that: In S1, the steps for synthesizing minoxidil-loaded liposomes are: S11, weighing soybean lecithin and cholesterol, dissolving them in an organic solvent, and removing the organic solvent to obtain liposomes, wherein the weight ratio of soybean lecithin to cholesterol is 1:1-3; S12, dissolving minoxidil, and then mixing it with liposomes, wherein the weight ratio of minoxidil to liposomes is 1:5-15.

7. The method for preparing the bioactive gel according to claim 5, characterized in that: In S2, the concentration of the oxidized dextran solution is 4-8wt%, the concentration of the carboxymethyl chitosan quaternary ammonium salt solution is 6-10wt%, and the volume ratio of the oxidized dextran solution to the carboxymethyl chitosan quaternary ammonium salt solution is 1:1-2.

8. The method for preparing the bioactive gel according to claim 5, characterized in that: In S2, oxidized dextran is prepared by oxidizing dextran, and carboxymethyl chitosan quaternary ammonium salt is prepared by grafting quaternary ammonium salt onto carboxymethyl chitosan.

9. The method for preparing the bioactive gel according to claim 5, characterized in that: In S11, the organic solvent is a mixed solution of methanol and chloroform, wherein the volume ratio of methanol to chloroform is 1:2-4.

10. Use of the bioactive gel according to any one of claims 1 to 4 or the preparation method according to any one of claims 5 to 9 in preparing a drug for treating hair loss.

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