Preparation method of photo-crosslinking hydrogel microneedle loaded with finasteride medicine
By preparing photocrosslinked hydrogel microneedles loaded with finasteride, the problems of slow onset and large side effects of existing androgenetic alopecia drugs have been solved. The drugs are uniformly dispersed and slowly released, making them suitable for female patients and improving the treatment effect.
Patent Information
- Application Number
- CN202511628314.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-07
- Publication Date
- 2026-02-10
AI Technical Summary
Existing treatments for androgenetic alopecia, such as minoxidil and finasteride, have problems such as slow onset of action, significant side effects, and limited efficacy. In particular, topical finasteride is not suitable for female patients, and oral finasteride may affect male function.
The photocrosslinked hydrogel microneedles loaded with finasteride were used to prepare methacryloyl hyaluronic acid and polyhydroxy fatty acid ester nanoparticles, which were then crosslinked with ultraviolet light to form hydrogel microneedles, thereby achieving uniform dispersion and sustained release of the drug.
It achieves uniform dispersion and slow release of finasteride, reduces systemic exposure, minimizes side effects, is suitable for female patients, and improves treatment efficacy.
Smart Images
Figure CN121489843A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of hydrogel preparation, specifically to the preparation of a photocrosslinked hydrogel microneedle for treating androgenetic alopecia. Background Technology
[0002] Androgenetic alopecia (AGA) is a common non-scarring type of hair loss. Data shows that the prevalence rate in Chinese men is 21.3%, while in women it is 6.0%. Furthermore, hair loss is increasingly affecting younger people, with 63.1% of those under 35 years old experiencing hair loss in my country alone. Currently, the U.S. Food and Drug Administration (FDA) has approved only two drugs for the treatment of AGA: minoxidil (MIN) and finasteride (FIN). However, topical MIN has a slow onset of action, can cause local scalp contact dermatitis, and has a high relapse rate after discontinuation; while FIN may have drawbacks during oral treatment, such as affecting male function, increasing the risk of depression, and being unsuitable for female patients. Both drugs have limited efficacy, therefore, exploring new treatment methods to improve drug efficacy is of significant clinical importance.
[0003] Topical finasteride (FIN) is considered an effective treatment option for alopecia areata (AGA) with relatively few side effects. To avoid the potential adverse reactions of oral administration, research on topical finasteride (FIN) for AGA has become increasingly focused. Results show that in male patients, compared with placebo, 0.25% topical finasteride (FIN) solution significantly improved hair count, with efficacy comparable to oral finasteride (FIN), while significantly reducing systemic exposure, having less impact on DHT concentration, and exhibiting good tolerability.
[0004] Hydrogels are highly malleable and can be molded into microneedles for transdermal drug delivery. As a novel type of microneedle, hydrogel microneedles exhibit excellent biocompatibility and mechanical properties, while also possessing the properties and advantages of hydrogels, including adhesion, moisturizing, waterproofing, mechanical properties, and degradation capabilities. Therefore, hydrogel microneedles can be completely removed from the skin after interaction, leaving no residue; and through their unique swelling properties, they can achieve minimally invasive collection of substances for human testing and sustained drug release. Summary of the Invention
[0005] The purpose of this invention is to provide a photocrosslinked hydrogel microneedle loaded with finasteride drug to solve the problems mentioned in the background art.
[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing photocrosslinked hydrogel microneedles loaded with finasteride drug, comprising the following steps: S1: Preparation of hydrogel; S2: Preparation of methacrylamide hyaluronic acid: Weigh hyaluronic acid and dissolve it in deionized water, then add methacrylic acid solution, add NaOH solution dropwise, adjust the pH to 8-9, and then stir the reaction. After the reaction solution returns to room temperature, centrifuge to collect the supernatant, dialyze for 3 days, and freeze-dry to obtain the product: S3: Preparation of F-PHA NPs: Finasteride (FIN) and polyhydroxyalkanoate (PHA) were weighed and dissolved in dichloromethane (DCM), and then the solution was added to the PVA solution. The mixture was sonicated to ensure thorough mixing, and then reacted at room temperature. After the reaction was completed, the mixture was centrifuged, the supernatant was removed, the solid was washed three times with deionized water, and finally freeze-dried to obtain the product. S4: Preparation of F-HAMA hydrogel microneedles: Methacrylamide hyaluronic acid (HAMA) was dissolved in PBS solution, and then finasteride (FIN) was added to the HAMA solution. The mixture was ultrasonically dispersed for a period of time to ensure thorough mixing. Then, the photoinitiator lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP) was added. The solution was repeatedly heated and concentrated in an oven. The hydrogel was obtained by irradiation with ultraviolet light. PVA solution was added and the solution was heated and concentrated once more.
[0007] Specifically, in step S2, the stirring temperature for preparing methacrylated hyaluronic acid is -4 to 10°C, and the stirring time is 5 to 30 hours.
[0008] Specifically, in step S2, the mass-to-volume ratio of hyaluronic acid, methacrylic acid, and deionized water is 0.5-2g:1-10ml:10-200ml, and the NaOH concentration is 1-10mol / L.
[0009] Specifically, in the S3 step of preparing F-PHANPs, the ultrasonic time is 1-10 min and the reaction time is 1-20 h.
[0010] Specifically, in step S3, the mass and volume ratio of finasteride (FIN), polyhydroxy fatty acid ester (PHA), dichloromethane (DCM) solution, and PVA solution in the preparation of oxidized hyaluronic acid is 0-25mg: 50-200mg: 1-10ml: 5-200ml.
[0011] Specifically, in step S4, the volume-to-mass ratio of methacrylamide hyaluronic acid (HAMA), PBS buffer, F-PHANPs, and LAP in the preparation of F-HAMA hydrogel microneedles is 1-10g: 10-500ml: 10-100mg: 10-100mg.
[0012] Specifically, in the preparation method of F-HAMA hydrogel microneedles, the heating and concentration temperature is 20-80℃, the concentration is repeated 1-5 times, and the ultraviolet light irradiation time is 1-30 min.
[0013] Compared with the prior art, the beneficial effects of the present invention are: 1. Using PHA-coated finasteride (FIN) nanoparticles, polyhydroxy fatty acid esters (PHA) not only achieve more sustained drug release but also have a gentler effect on tissues. In addition, their degradation products are safe and non-genotoxic, making them more suitable for the biomedical field.
[0014] 2. The prepared methacrylamide hyaluronic acid (HAMA) can rapidly form a hydrogel by external ultraviolet light irradiation. The internal morphology of the hydrogel will not be destroyed by stirring, which allows the drug to be more evenly dispersed inside the hydrogel and not to be destroyed by external forces. Attached Figure Description
[0015] Figure 1 The images show the 1H NMR spectrum and infrared spectrum of hyaluronic acid (HA) and methacrylamide hyaluronic acid (HAMA) in Example 1 of this invention.
[0016] Figure 2 The images show scanning electron microscope images and swelling performance diagrams of the hydrogel in Embodiment 1 of the present invention.
[0017] Figure 3 The image shows the size distribution curve and scanning electron microscope image of F-PHANPs in Embodiment 1 of the present invention.
[0018] Figure 4 The image shows the drug release curve of finasteride (FIN) in the F-HAMA hydrogel in Example 1 of this invention and the mechanical properties of the hydrogel.
[0019] Figure 5 This is a scanning electron microscope image showing the changes of the hydrogel microneedles under different external forces in Embodiment 1 of the present invention.
[0020] Figure 6 This is a biocompatibility experiment diagram of the hydrogel and hydrogel microneedles in Embodiment 1 of the present invention. Detailed Implementation
[0021] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example
[0022] Please see Figures 1-6 This invention provides a technical solution: the preparation of FIN-loaded photocrosslinked hydrogel microneedles, comprising the following steps: S1: Preparation of hydrogel; A1: Preparation of Methacrylamide Hyaluronic Acid (HAMA): Hyaluronic acid (HA) (1 g, 20-40 w Da) was completely dissolved in deionized water (100 mL). Then, methacrylic acid solution (5 mL) was added to the HA solution, and NaOH solution (1 M) was added dropwise to adjust the pH of the mixture to 8-9. The mixture was stirred at 4°C for 24 h. After the reaction solution returned to room temperature, the reaction mixture was centrifuged at 5000 rpm for 10 minutes, and the supernatant was collected. The mixture was dialyzed in a dialysis bag (molecular weight cutoff 8000-14000 Da) for 3 days, with the water changed 3 times daily. The resulting white, spongy solid, HAMAA, was obtained by freeze-drying.
[0023] A2: Preparation of F-PHA NPs: FIN (10 mg) and PHA (100 mg) were dissolved in dichloromethane (DCM, 10 mL), and then the solution was added to 1% PVA solution (50 mL). The mixture was sonicated for 5 min to ensure thorough mixing, and then reacted at room temperature for 8 h. After the reaction was completed, the mixture was centrifuged at 12000 rpm for 10 min, the supernatant was removed, the solid was washed three times with deionized water, and finally freeze-dried to obtain the product.
[0024] A3: Preparation of methacrylamide hyaluronic acid (HAMA) hydrogel: methacrylamide hyaluronic acid (HAMA) was dissolved in PBS solution (1% w / v), and 0.3% w / v of photoinitiator lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP) was added. The methacrylamide hyaluronic acid (HAMA) hydrogel was prepared by irradiation with ultraviolet light for 1 min.
[0025] A4: Preparation of F-HAMA hydrogel: Methacrylamide hyaluronic acid (HAMA) was dissolved in PBS solution (1% w / v), and then finasteride (FIN) was added to the HAMA solution (0.25%). The mixture was ultrasonically dispersed for 10 min to ensure thorough mixing. Then, 0.3% w / v of the photoinitiator lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP) was added, and the mixture was irradiated with ultraviolet light for 1 min to prepare F-HAMA hydrogel.
[0026] like Figure 1 The figures show the 1H NMR spectra of hyaluronic acid (HA) and methacrylamide hyaluronic acid (HAMA) prepared in Example 1, as well as the infrared spectra of hyaluronic acid (HA), methacrylic anhydride, and methacrylamide hyaluronic acid. The NMR spectrum of methacrylamide hyaluronic acid (HAMA) shows three new peaks at 1.91, 5.71, and 6.15 ppm, confirming the successful preparation of methacrylamide hyaluronic acid (HAMA). The infrared spectrum of methacrylamide hyaluronic acid (HAMA) shows a peak at 1720 cm⁻¹. -1 A new characteristic peak appeared, which is attributed to the stretching vibration peak of the aldehyde group.
[0027] Figure 2 The images shown are scanning electron microscope images and swelling performance diagrams of the hydrogel in Example 1. The hydrogel exhibits a three-dimensional network structure. Figure 2 a) such as Figure 2 As shown in b, the methacryloyl hyaluronic acid (HAMA) hydrogel exhibits significant water absorption capacity. In the first hour, the hydrogel shows a strong water absorption rate, gradually approaching saturation, with the equilibrium swelling ratio eventually stabilizing at approximately 3600%.
[0028] Figure 3 The images show the size distribution curve and scanning electron microscope image of F-PHA NPs in Example 1. The size distribution of the nanoparticles is mostly between 100-200 nm.
[0029] Figure 4 The figures show the drug release curve of FIN in the F-HAMA hydrogel and the mechanical properties of the hydrogel in Example 1. Figure 4The study showed that finasteride was released explosively in the first 5 days of the hydrogel, followed by a slow release after 5 days. Overall, about 70% was released by 8 days, and the release continued slowly thereafter. Both F-HAMA and methacryloyl hyaluronic acid (HAMA) exhibited excellent mechanical strength. Compared with methacryloyl hyaluronic acid (HAMA) hydrogel, F-HAMA showed a higher compressive strain, rupturing at 58% compressive strain, while methacryloyl hyaluronic acid (HAMA) ruptured at 54%. In addition, the maximum compressive strength of F-HAMA increased from 13.36 kPa to 25.78 kPa compared with methacryloyl hyaluronic acid (HAMA) hydrogel.
[0030] Figure 5 This is a scanning electron microscope image showing the changes in the hydrogel microneedles under different external forces in Example 1. Pressures of 100 g and 200 g were applied to the two types of microneedles, respectively. The results are as follows... Figure 5 As shown, when a pressure of 100g was applied, both methacryloyl hyaluronic acid (HAMA) MN and F-HAMA MN exhibited a small number of needle tip breakages or slight deformations, with proportions of approximately 11% and 7% of the total, respectively. However, when a pressure of 200g was applied, both microneedles showed more significant deformation and breakage. Nevertheless, the damage rate of F-HAMA MN was still lower than that of methacryloyl hyaluronic acid (HAMA) MN, at 17% and 32%, respectively.
[0031] Figure 6 This image shows the biocompatibility experiment of the hydrogel and hydrogel microneedles in Example 1. Compared with the control group (cell viability 98.2%), the relative cell viability of each experimental group decreased slightly, at 85.94%±3.34%, 84.96%±2.32%, and 83.34%±7.67%, respectively. Nevertheless, all experimental groups still showed high cell survival rates, indicating that the prepared hydrogel has good biocompatibility.
[0032] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
Claims
1. A method for preparing photocrosslinked hydrogel microneedles loaded with finasteride drug, characterized in that, Includes the following steps: S1: Preparation of hydrogel; S2: Preparation of methacrylamide hyaluronic acid (HAMA): Hyaluronic acid (HA) was weighed and dissolved in deionized water, then methacrylic acid solution was added, and NaOH solution was added dropwise to adjust the pH to 8-9. The reaction was then stirred. After the reaction solution returned to room temperature, the supernatant was collected by centrifugation, dialyzed for 3 days, and then freeze-dried to obtain the product. S3: Preparation of F-PHANPs: Finasteride (FIN) and polyhydroxyalkanoate (PHA) were weighed and dissolved in dichloromethane (DCM), and then the solution was added to the PVA solution. The mixture was sonicated to ensure thorough mixing, and then reacted at room temperature. After the reaction was completed, the mixture was centrifuged, the supernatant was removed, the solid was washed three times with deionized water, and finally freeze-dried to obtain the product. S4: Preparation of F-HAMA hydrogel microneedles: Methacrylamide hyaluronic acid (HAMA) was dissolved in PBS solution, and then finasteride (FIN) was added to the HAMA solution. The mixture was ultrasonically dispersed for a period of time to ensure thorough mixing. Then, the photoinitiator lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP) was added. The solution was repeatedly heated and concentrated in an oven. The hydrogel was obtained by irradiation with ultraviolet light. PVA solution was added and the solution was heated and concentrated once more.
2. The method for preparing a photocrosslinked hydrogel microneedle loaded with finasteride according to claim 1, characterized in that, In step S2, which involves the preparation of methacryloyl hyaluronic acid (HAMA), the stirring temperature is -4 to 10°C and the stirring time is 5 to 30 hours.
3. The method for preparing a photocrosslinked hydrogel microneedle loaded with finasteride according to claim 1, characterized in that, In step S2, which prepares methacrylated hyaluronic acid (HAMA), the mass-to-volume ratio of hyaluronic acid (HA), methacrylic acid, and deionized water is 0.5-2g:1-10ml:10-200ml, and the NaOH concentration is 1-10mol / L.
4. The method for preparing a photocrosslinked hydrogel microneedle loaded with finasteride according to claim 1, characterized in that, In the S3 step of preparing F-PHANPs, the ultrasonic time is 1-10 min and the reaction time is 1-20 h.
5. The method for preparing a photocrosslinked hydrogel microneedle loaded with finasteride according to claim 1, characterized in that, In the S3 step of preparing F-PHANPs, the mass and volume ratio of finasteride (FIN), polyhydroxy fatty acid ester (PHA), dichloromethane (DCM) solution, and PVA solution is 0-25mg: 50-200mg: 1-10ml: 5-200ml.
6. The method for preparing a photocrosslinked hydrogel microneedle loaded with finasteride according to claim 1, characterized in that, In step S4, the volume-to-mass ratio of methacryloyl hyaluronic acid (HAMA), PBS buffer, F-PHANPs, and LAP in the preparation of F-HAMA hydrogel microneedles is 1-10g: 10-500ml: 10-100mg: 10-100mg.
7. The method for preparing a photocrosslinked hydrogel microneedle loaded with finasteride according to claim 1, characterized in that, The method for preparing F-HAMA hydrogel microneedles involves heating and concentrating at a temperature of 20-80℃, concentrating 1-5 times, and irradiating with ultraviolet light for 1-30 minutes.