A flexible microneedle patch for photodynamic therapy and its preparation method

Abstract

The present invention discloses a flexible microneedle patch for photodynamic therapy, which includes patch needle tips, a patch substrate, a wireless light source, and a light source induction unit; the patch needle tips are fixed on the patch substrate, and the wireless light source is fixed in the patch substrate; the patch needle tips and the patch substrate respectively use a polymerizable polymer as a matrix and are both cured by ultraviolet light; the wireless light source is used for photodynamic assisted therapy and simultaneously promotes the absorption and release of drugs; the light source induction unit realizes the on-off control of the wireless light source by using the principle of electromagnetic induction. The preparation method includes the following steps: preparation of a PDMS mold, preparation of patch needle tips, and preparation of a flexible substrate of the microneedle patch carrying an LED light source. It can achieve simultaneous light-assisted therapy, which can promote the release and diffusion absorption of some drugs and also perform photodynamic therapy on the target affected area.

Description

Technical Field

[0001] The present invention relates to the technical field of microneedles, and particularly relates to a flexible microneedle patch for photodynamic therapy and a preparation method thereof. Background Art

[0002] Microneedle transdermal drug delivery is a new and efficient transdermal drug delivery technology. Microneedles with sufficient length and mechanical strength can pierce the stratum corneum of the skin, breaking the barrier effect of the stratum corneum on drug delivery. After the application of microneedles, the drug delivery efficiency can be significantly improved. Compared with traditional transdermal drug delivery systems, microneedle drug delivery is a painless method because it does not stimulate the nerves of deep tissues. The most commonly used microneedle materials are metals, silicon, and polymers. Metal microneedles cause immune inflammation and have safety problems of intradermal retention caused by easy fracture, while silicon materials are fragile and have poor biocompatibility. In contrast, polymer microneedles have good biocompatibility and are biodegradable, have sufficient mechanical strength to pierce the stratum corneum of the skin, can achieve good flexibility, have simple processing methods, and relatively low processing costs. At the same time, they can achieve drug-loading capacity with drug sustained release. These advantages make polymer microneedles a research hotspot in the current field of transdermal drug delivery technology and have more development prospects.

[0003] Currently, the preparation methods of microneedles mainly include various methods such as microinjection compression molding process, ultraviolet light curing molding process, hot embossing molding process, and casting molding process. Among them, ultraviolet light curing molding is an automated operation by machine, which can reduce labor costs; there is no solvent volatilization during use, and it will not cause air pollution; the microneedle preparation time is greatly shortened, improving production efficiency.

[0004] Photodynamic therapy, also known as photochemotherapy or photobiological therapy, is widely used in multiple clinical disciplines, such as pediatrics, obstetrics and gynecology, and dermatology and other clinical fields. Photodynamic therapy is widely used to treat various benign tumors, malignant tumors, precancerous lesions, and certain infectious diseases, such as hemangioma, carcinoma in situ or precancerous lesions in children. Obstetrics and gynecology and dermatology often use photodynamic therapy to treat condyloma acuminata in the vulva, genital area, perianal area or within the anus. Photodynamic therapy is a treatment method that uses the photochemical reaction of photosensitizers in the human body to produce light after receiving specific laser irradiation, achieving the effect of removing tumors or removing infectious microorganisms. The treatment effect is relatively good, the effective rate is relatively high, and the recurrence rate is relatively low. Photodynamic therapy is a relatively good treatment method. Summary of the Invention

[0005] One technical problem solved by the present invention is a flexible microneedle patch for photodynamic therapy;

[0006] Another technical problem solved by the present invention is a preparation method of a flexible microneedle patch for photodynamic therapy; it can achieve light-assisted therapy while administering drugs through microneedles, which can promote the release and diffusion absorption of some drugs, and can also perform photodynamic therapy on the target affected area.

[0007] To achieve the above technical objectives, the technical solutions adopted by the present invention are as follows:

[0008] A flexible microneedle patch for photodynamic therapy of the present invention includes a patch tip 1, a patch base 2, a wireless light source 3, and a light source induction unit 4; the patch tip 1 is fixed on the patch base 2, and the wireless light source 3 is fixed in the patch base 2; the patch tip 1 and the patch base 2 respectively use a polymer-soluble polymer as a matrix and are both cured by ultraviolet light; the wireless light source 3 is used for photodynamic-assisted therapy and simultaneously promotes the absorption and release of drugs; the light source induction unit 4 uses the principle of electromagnetic induction to realize the on-off control of the wireless light source 3.

[0009] Further, the polymer-soluble polymer of the patch tip 1 is formed by fully mixing hydroxyethyl acrylate solution, hexanediol diacrylate solution, photoinitiator, and photocurable composite resin and then curing with ultraviolet light.

[0010] Further, the polymer-soluble polymer of the patch base 2 is formed by mixing hydroxyethyl acrylate solution, hexanediol diacrylate solution, and photoinitiator and then curing with ultraviolet light.

[0011] Further, the wireless light source 3 uses a micro wireless LED light source wrapped with a coil.

[0012] Further, the light source induction unit 4 is composed of a transmitting coil and a transmitting coil driving board.

[0013] Further, the height of the patch tip 1 is 200 - 2000 microns, the bottom diameter is 100 - 500 microns, the tip gradually tapers, and the tip width is 10 - 50 microns.

[0014] Further, the patch tip 1 is formed by mixing a photocurable resin with a mass fraction of 70% and a hydroxyethyl acrylate solution, hexanediol diacrylate solution, and photoinitiator solution with a mass fraction of 30%.

[0015] Further, different components of photocurable composite resin are added to the polymer-soluble polymer of the patch base 2 according to specific requirements to prepare bases with different flexibilities.

[0016] A preparation method for a flexible microneedle patch for photodynamic therapy includes the following steps:

[0017] 1) Preparation of PDMS mold: The prepolymer of polydimethylsiloxane and the curing agent are fully mixed and degassed in a vacuum. Then, the degassed mixed solution is poured into a pre-prepared microneedle patch for mold replication, and then placed in the air to dry.

[0018] 2) Preparation of patch needle tips: First, the high-molecular soluble polymer of the patch needle tips is fully mixed, and then dropped into the pre-prepared PDMS mold. After sufficient grinding, vacuum treatment is carried out to allow the solution to fully enter the patch needle tip part. Then, the solution at the base part of the mold is wiped clean, leaving only the solution at the patch needle tip part, and then the remaining patch needle tips are cured by ultraviolet light.

[0019] 3) Preparation of microneedle patch flexible substrate with LED light source: First, the fully mixed solution of the high-molecular soluble polymer of the patch substrate is dropped into the PDMS substrate. Then, while the patch substrate is cured by ultraviolet light, the wireless light source is placed in the PDMS mold substrate for ultraviolet light curing. The wireless light source is fixed in the substrate while the patch substrate is cured by ultraviolet light.

[0020] The beneficial effects of adopting the above technical solutions are as follows:

[0021] 1. Simultaneous photo-assisted treatment can promote the release and diffusion absorption of some drugs, and can also perform photodynamic therapy on the target affected area;

[0022] 2. The preparation process is automated, the processing method is simple, the processing cost is low, and the production efficiency is high; there is no solvent volatilization during use, and air pollution will not be caused. Description of the drawings

[0023] Figure 1 It is a schematic diagram of a flexible microneedle patch for photodynamic therapy;

[0024] Figure 2 It is a schematic diagram of a flexible microneedle patch with a light source;

[0025] Figure 3 It is a cross-sectional view of a flexible microneedle patch;

[0026] Figure 4 It is a schematic diagram of a wireless light source;

[0027] Figure 5 It is a forward bending diagram of a flexible microneedle patch;

[0028] Figure 6 It is a reverse bending diagram of a flexible microneedle patch;

[0029] Figure 7 It is a schematic diagram of a mold for the preparation method of a flexible microneedle patch for photodynamic therapy;

[0030] In the figure: 1. patch needle tip, 2. patch base, 3. wireless light source, 4. light source sensing unit, 5. LED light source, 6. coil. DETAILED DESCRIPTION

[0031] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0032] like Figure 1 As shown, the flexible microneedle patch for photodynamic therapy of the present invention comprises a patch needle tip 1, a patch substrate 2, a wireless light source 3, and a light source sensing unit 4; the patch needle tip 1 is fixed on the patch substrate 2, and the wireless light source 3 is fixed in the patch substrate 2;

[0033] The patch needle tip 1 and the patch base 2 respectively use high molecular soluble polymer as the matrix, and are both formed by ultraviolet light curing; the high molecular soluble polymer of the patch needle tip 1 is formed by ultraviolet curing after fully mixing hydroxyethyl acrylate solution, hexanediol diacrylate solution, photoinitiator and photocurable composite resin.

[0034] The high molecular weight soluble polymer of the patch substrate 2 is obtained by mixing hydroxyethyl acrylate solution, hexanediol diacrylate solution and a photoinitiator and then curing with ultraviolet light.

[0035] The wireless light source 3 is used for photodynamic assisted therapy and promotes the absorption and release of drugs; the wireless light source 3 is a miniature wireless LED light source wrapped with a coil.

[0036] The light source sensing unit 4 uses the electromagnetic induction principle to realize the switch control of the wireless light source 3; the light source sensing unit 4 is composed of a transmitting coil and a transmitting coil driving board.

[0037] The patch needle tip 1 has a height of 200-2000 microns, a bottom diameter of 100-500 microns, a gradually tapering tip, and a tip width of 10-50 microns. The patch needle tip 1 is a mixture of 70% by mass of a photocurable resin and 30% by mass of a hydroxyethyl acrylate solution, a hexanediol diacrylate solution, and a photoinitiator solution.

[0038] The patch substrate 2 is a high molecular weight soluble polymer, and light-curable composite resins of different components are added according to specific needs to prepare substrates with different flexibility.

[0039] A method for preparing a flexible microneedle patch for photodynamic therapy comprises the following steps:

[0040] 1) Preparation of PDMS mold: The prepolymer of polydimethylsiloxane and the curing agent are fully mixed and degassed in vacuum. Then, the degassed mixed solution is poured into the previously prepared microneedle patch for mold replication, and then left to dry in air.

[0041] 2) Preparation of patch needle tips: First, the high - molecular soluble polymer of the patch needle tips is fully mixed, then dropped into the previously prepared PDMS mold. After sufficient grinding, vacuum treatment is carried out to allow the solution to fully enter the patch needle tip part. Then, the solution in the base part of the mold is wiped clean, leaving only the solution in the patch needle tip part. Then, ultraviolet light curing is performed on the remaining patch needle tips.

[0042] 3) Preparation of flexible substrate of microneedle patch carrying LED light source: First, the fully mixed solution of the high - molecular soluble polymer of the patch substrate is dropped into the PDMS substrate. Then, while performing ultraviolet curing on the patch substrate, the wireless light source is placed in the PDMS mold substrate for ultraviolet light curing. The wireless light source is fixed in the substrate while the patch substrate is being ultraviolet - cured.

[0043] Example 1

[0044] A flexible microneedle patch for photodynamic therapy of the present invention mainly uses hydroxyethyl acrylate, hexanediol diacrylate, photoinitiator and ultraviolet - curable composite resin as raw materials. By separately preparing the patch needle tips and the patch substrate, the patch needle tips are hard and the substrate is soft, which can better adhere to the skin and achieve precise and efficient drug delivery. The softness of the patch substrate can also be changed by changing the proportion of the ultraviolet - curable composite resin.

[0045] The patch needle tips are formed by ultraviolet curing after fully mixing a solution of hydroxyethyl acrylate, a solution of hexanediol diacrylate, a photoinitiator and an ultraviolet - curable composite resin.

[0046] The patch needle tips are a mixture of a photocurable resin with a mass fraction of 70%, a solution of hydroxyethyl acrylate with a mass fraction of 30%, a solution of hexanediol diacrylate and a photoinitiator solution.

[0047] When preparing the patch needle tips, the solution of hydroxyethyl acrylate, the solution of hexanediol diacrylate, the initiator and the ultraviolet - curable composite resin need to be fully stirred for about 10 minutes to completely dissolve the colloidal ultraviolet - curable composite resin into a solution state.

[0048] The flexible microneedle patch can coat drugs on the surface of the microneedles and can achieve precise drug delivery to the target affected area.

[0049] The patch needle tips of the flexible microneedle patch can penetrate the skin or organ to play a role in fixing the LED light source.

[0050] The patch substrate is prepared by mixing hydroxyethyl acrylate solution, hexanediol diacrylate solution and a photoinitiator and then curing with ultraviolet light.

[0051] When making the patch base, light-curing composite resins of different components can be added according to specific needs to make a patch base with different required flexibility.

[0052] The light source used in the present invention adopts a relatively low-power LED light source, which will not cause serious heat generation even if it emits light for a long time. In addition, this light source does not require external wires and can achieve near-field wireless control of the light source.

[0053] When the microneedle patch equipped with a light source in the present invention is used, it is only necessary to keep the microneedle patch about 15 cm above or below the wireless power supply coil to enable the LED light source to emit light.

[0054] This microneedle patch can promote drug release and absorption through illumination by LED light sources, and can also perform light-assisted therapy.

[0055] The LED light source in this microneedle patch uses the principle of electromagnetic induction to achieve wireless control switching of the light source, avoiding infection and other risks caused by external wires.

[0056] The UV curing process used in this microneedle patch can achieve rapid molding of microneedles. It only takes about 15 minutes to make a piece of microneedle, realizing rapid mass production.

[0057] When preparing the PDMS mold, the polydimethylsiloxane (PDMS) prepolymer and the curing agent are first thoroughly mixed and degassed in a vacuum for 20 minutes. The degassed mixed solution is then poured into the previously prepared microneedle patch for mold casting and then placed in the air to dry naturally for 48 hours.

[0058] The above description is only a preferred specific implementation of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that a person skilled in the art can think of within the technical scope disclosed in the present invention should be included in the protection scope of the present invention.

Claims

1. A flexible microneedle patch for photodynamic therapy, characterized in that, include: Patch needle tip (1), patch substrate (2), wireless light source (3), light source sensing unit (4); The patch needle tip (1) is fixed on the patch substrate (2), and the wireless light source (3) is fixed in the patch substrate (2); The patch needle tip (1) and the patch base (2) respectively use high molecular weight soluble polymers as matrices, and are both cured by ultraviolet light; The wireless light source (3) is used for photodynamic assisted therapy and promotes the absorption and release of drugs; The light source sensing unit (4) uses the principle of electromagnetic induction to realize on / off control of the wireless light source (3); The high molecular weight soluble polymer of the patch needle tip (1) is prepared by fully mixing hydroxyethyl acrylate solution, hexanediol diacrylate solution, photoinitiator and photocurable composite resin and then ultraviolet curing; The high molecular weight soluble polymer of the patch substrate (2) is prepared by mixing hydroxyethyl acrylate solution, hexanediol diacrylate solution and a photoinitiator and then curing with ultraviolet light; The wireless light source (3) adopts a miniature wireless LED light source (5) wound with a coil (6); The light source sensing unit (4) is composed of a transmitting coil and a transmitting coil driving board; The patch needle tip (1) has a height of 200-2000 microns, a bottom diameter of 100-500 microns, a tip that gradually tapers, and a tip width of 10-50 microns; The patch needle tip (1) is formed by mixing 70% by mass of a photocurable resin and 30% by mass of a hydroxyethyl acrylate solution, a hexanediol diacrylate solution, and a photoinitiator solution; The patch substrate (2) is a high molecular weight soluble polymer to which light-curable composite resins of different components are added according to specific needs to prepare substrates of different flexibility.

2. A method for preparing the flexible microneedle patch for photodynamic therapy according to claim 1, comprising the following steps: 1) Preparation of PDMS mold: The prepolymer of polydimethylsiloxane and the curing agent are fully mixed and degassed in a vacuum, and then the degassed mixed solution is poured into the previously prepared microneedle patch for mold turning, and then placed in the air to dry; 2) Preparation of patch needle tip: First, the high molecular soluble polymer of the patch needle tip is fully mixed, and then dripped into the pre-prepared PDMS mold. After sufficient grinding, vacuum treatment is performed to allow the solution to fully enter the needle tip. Then, the solution at the base of the mold is wiped clean, leaving only the solution at the needle tip, and then the remaining patch needle tip is UV-cured; 3) Preparation of a microneedle patch flexible substrate equipped with an LED light source: First, a fully mixed solution of a high-molecular-weight soluble polymer of the patch substrate is dripped into the PDMS substrate, and then the wireless light source is placed in the PDMS mold substrate while the patch substrate is UV-cured and UV-cured. While the patch substrate is UV-cured, the wireless light source is fixed in the substrate.

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