An iontophoresis gel contact lens and a method for manufacturing the same
By designing an iontophoresis gel scleral contact lens and fabricating it using printed electronics and DLP photopolymerization technology, the problem of complex structure and low drug delivery efficiency of existing devices has been solved. This achieves efficient drug penetration and sustained release, and improves the convenience and safety of drug delivery.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- ZHONGSHAN FLASHLIGHT POLYTECHNIC
- Filing Date
- 2023-09-21
- Publication Date
- 2026-06-30
AI Technical Summary
Existing iontophoresis ocular drug delivery devices are complex in structure, have low ease of use, lack effective drug delivery methods, and have low drug delivery efficiency and controllability. Furthermore, the manufacturing process limits the optimization of the devices.
An iontophoresis gel scleral contact lens was designed, comprising a contact lens skeleton, a drug-loaded layer, an electrode layer, and a flexible material. The electrode layer and sensor were fabricated using printed electronics technology, and nano-sustained-release drug microspheres were deposited on the flexible material. Combined with DLP photocuring technology, a gel layer was formed, which simplifies the device structure and improves drug delivery efficiency.
It achieves efficient drug penetration and sustained release, simplifies the drug administration process, improves patient compliance and drug efficacy, reduces drug loss, and lowers the frequency of drug administration.
Smart Images
Figure CN117281683B_ABST
Abstract
Description
[Technical Field]
[0001] This invention relates to the field of iontophoresis technology, and in particular to an iontophoresis gel scleral contact lens and its preparation method. [Background Technology]
[0002] Iontoosmotic drug delivery is a non-invasive drug delivery technique based on the principle that like charges repel and unlike charges attract. During use, charged drugs are propelled into the eyeball by electrodes carrying the same charge under the influence of an electric field, facilitating the drug's crossing of the ocular barrier and penetration into the eye. This method offers convenient drug delivery, minimal systemic adverse reactions, and improved drug permeability and targeting.
[0003] Problems with existing iontophoresis non-invasive ocular drug delivery methods include:
[0004] Iontoosmotic ocular drug delivery devices are complex in structure and have low usability. The circuitry of existing electronic electroosmotic drug delivery devices is manufactured using traditional electronic component processing methods based on etching-electroplating technology, while the physical support structure consists of plastic supports and silicone rings fabricated through molding. Due to the limitations of these manufacturing methods, ocular drug delivery devices are large in size and cannot achieve effective fit with the patient. This results in poor usability, a poor patient experience, and compromised drug delivery efficacy. Therefore, research is needed to improve the design and manufacturing process to optimize and upgrade the form of iontoosmotic drug delivery devices.
[0005] Iontoosmosis lacks effective drug delivery methods, and improvements are needed in drug delivery efficiency, controllability of drug initiation and discontinuation, and pH monitoring of the drug ion solution during drug delivery. Drug delivery efficiency can be divided into drug penetration and delivery efficiency and overall drug utilization. Iontoosmosis technology undoubtedly increases drug penetration and delivery efficiency, but it does not function as a drug carrier. Drugs are mostly applied externally, thus failing to address drug loss due to ocular physiological barriers, including tear film barriers such as tear flow, nasolacrimal duct drainage, and blink reflex, as well as mucus barriers, resulting in low overall utilization. Reducing the frequency of manual drug replenishment and enhancing drug retention and sustained release are important directions for optimizing ocular iontoosmosis devices.
[0006] The anatomy of the eyeball can be divided into the anterior segment and the posterior segment, with the lens as the boundary. The anterior segment includes the cornea, conjunctiva, iris, ciliary body, aqueous humor, and lens, while the posterior segment includes the sclera, choroid, retina, and vitreous body. The cornea, conjunctiva, and sclera form the outermost layer of the eyeball, preventing the entry of exogenous substances and making the eyeball a relatively closed organ. The sclera region has relatively low drug delivery resistance; therefore, iontophoresis in this area can reduce the barrier layer and effectively improve drug delivery efficiency.
[0007] Therefore, the challenge lies in providing an effective drug delivery method that increases drug penetration and delivery efficiency while addressing drug loss due to ocular physiological barriers, including tear film barriers and mucus barriers such as tear flow, nasolacrimal duct drainage, and blink reflex, resulting in low overall utilization rates through scleral iontophoresis drug delivery. [Summary of the Invention]
[0008] To address the shortcomings of existing electroosmotic ocular drug delivery devices, such as complex structure, low usability, lack of effective drug delivery methods, low drug delivery efficiency and controllability of drug delivery start and stop, and limitations imposed by manufacturing and processing methods, this invention proposes an ionoosmotic gel scleral contact lens and its preparation method that increases drug penetration and delivery efficiency, is not limited by manufacturing and processing methods, and has an effective drug delivery method.
[0009] This invention is achieved by the following technical solution:
[0010] An iontophoresis gel scleral contact lens includes a contact lens frame. The contact lens frame is provided with a drug-loaded layer, an electrode layer and a flexible material covering the electrode layer from the side closest to the sclera outward. The outer side of the contact lens frame is also covered with a gel layer. The drug-loaded layer (2) is coated on the electrode layer (3). The drug-loaded layer is a polymer porous microsphere loaded with a nano-sustained-release drug.
[0011] Preferably, the drug-carrying layer (2) may also be ionic gelatin nanoparticles or polymer micelles containing drug components.
[0012] Preferably, the method for preparing the flexible material includes the following steps: immersing cellulose paper in an acrylamide solution, heating it under a nitrogen atmosphere, removing it, drying it, and cutting it to obtain hydrogel-reinforced cellulose paper, i.e., the flexible material.
[0013] Preferably, the electrode layer is an electrode pattern formed by inkjet printing conductive ink onto the surface of the flexible material and then sintering it at a low temperature. The electrode layer is disposed around the periphery of the sclera region of the eyeball. The contact lens frame also includes a sensor disposed on one side of the electrode layer near the center for measuring pH changes during iontophoresis. The electrode layer contains at least one electrode structure, which is connected to an external current or voltage source. Each electrode structure may have the same or different polarities to provide iontophoresis voltage.
[0014] Preferably, the sensor preparation method includes the following steps: using a flexible material as a substrate, applying protective film tape to both sides, drilling holes and adding conductive carbon paste to connect the front and back sides, printing working electrode lines, insulating ink, carbon electrode lines, Ag / AgCl reference electrode lines, and insulating ink on the front side, and then printing contrast electrode lines and insulating ink on the back side to obtain the sensor.
[0015] Preferably, the gel layer (5) is further provided with through holes (7) through the drug-carrying layer (2) for gas discharge and drug addition.
[0016] A method for preparing an iontophoresis gel scleral contact lens as described in any of the preceding claims includes the following steps:
[0017] S1. Preparation of flexible materials;
[0018] S2. On the surface of the flexible material obtained in the step, conductive ink is used to inkjet print the corresponding electrode layer on the periphery of the sclera region of the eyeball and sinter it to obtain a flexible material containing the electrode layer.
[0019] S3. Take the flexible material containing the electrode layer obtained in the previous step, coat the drug-loaded layer onto the electrode layer of the flexible material, and after drying, obtain the contact lens skeleton.
[0020] S4. Immerse the contact lens skeleton from the previous step into the gel solution, use a DLP device to fix and pull it out for printing, and use ultraviolet light to cure it to form a gel layer covering its surface, thus obtaining a gel scleral contact lens.
[0021] Preferably, in step S2, the conductive ink material is a metal with a lower ionization tendency than hydrogen, and the metal is preferably nano-silver conductive ink to prevent gas evolution during ion electroosmosis.
[0022] Preferably, in step S4, the main components of the gel cured during the DLP process include: 2-hydroxyethyl methacrylate, 1-vinyl-2-pyrrolidone, silane coupling agent, thermoplastic polyolefin elastomer, polyethylene glycol diacrylate, and prepolymer.
[0023] Preferably, in step S1, the heating temperature is 30-90℃ and the heating time is 3-9h; in step S2, the heating temperature is 100-150℃ and the heating time is 10-30min.
[0024] Iontoosmosis generates an electric field through two or more electrodes, causing the charged active substances in the electric field to migrate towards the target tissue under the influence of like charges repelling and unlike charges attracting, thereby achieving the therapeutic purpose. Iontoosmosis is a non-invasive technique that is easy to operate, has a definite curative effect, high patient compliance, and is widely used in clinical practice.
[0025] Compared with the prior art, the present invention has the following advantages:
[0026] This invention proposes an iontophoresis gel scleral contact lens, comprising a contact lens frame, a polymer porous microsphere drug-carrying layer containing sustained-release nanoparticles, an electrode layer, and a flexible material covering the electrode layer, with a gel layer further covering the outer side of the contact lens frame. This iontophoresis gel scleral contact lens has a simple structure, facilitates convenient and safe drug delivery, minimizes eye damage, allows patients to self-administer medication, directly delivers the drug to the scleral lesion site, avoids adverse reactions in other tissues or systemically, and has a sustained-release function to reduce the frequency of administration.
[0027] This invention proposes a method for preparing iontophoresis gel scleral contact lenses. By using printed electronics technology, an electrode layer and a sensor are printed on a prepared flexible substrate material to form a microelectrode cellulose paper. Nanoparticle sustained-release drugs are deposited on the surface of the microelectrode cellulose paper to form a microsphere drug-carrying layer, thus obtaining a gel cellulose skeleton. This skeleton is then immersed in a gel solution, and the scleral contact lens is prepared by DLP photocuring technology. This method has a simple preparation process and is highly operable. [Attached Image Description]
[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below.
[0029] Figure 1 This is a schematic diagram of the scleral contact lens forming process of the present invention;
[0030] Figure 2 This is a schematic diagram illustrating the technical route and experimental scheme of the present invention;
[0031] Figure 3 This is a schematic diagram of the scleral contact lens structure of the present invention;
[0032] Figure 4 This is a cross-sectional schematic diagram of the scleral contact lens of the present invention;
[0033] Figure 5 This is a test diagram of iontophoresis drug delivery using the scleral contact lens of the present invention.
Detailed Implementation Methods
[0034] To make the technical problems solved, the technical solutions, and the beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
[0035] Example 1:
[0036] An iontophoretic gel scleral contact lens and its preparation method, the method comprising the following steps:
[0037] (1) Take a piece of cellulose paper and immerse it in an acrylamide solution with a mass ratio of methylene bisacrylamide to potassium sulfate of 150:1. Heat it continuously for 6 hours under a nitrogen atmosphere at 60°C. After heating, transfer it to a vacuum drying oven to dry. Once drying is complete, hydrogel-reinforced cellulose paper is obtained. Cut the hydrogel-reinforced cellulose paper to the size that matches the scleral contact lens to obtain a flexible matrix material.
[0038] (2) Take a flexible substrate material and use nano-silver conductive ink to print two electrodes, anode and cathode, on the surface of the substrate to form a dual electrode pattern. After sintering at 120°C for 20 minutes, the electrode layer with dual electrode structure is obtained. Protective film tape is applied to the front and back sides, and then holes are drilled and conductive carbon paste is added (to connect the front and back sides). The working electrode line (WE line), insulating ink, carbon electrode line, Ag / AgCl reference electrode line (RE line), and insulating ink are printed on the front side. Then the control electrode line (CE line) and insulating ink are printed on the back side. After sintering at 120°C for 20 minutes, the pH sensor is obtained.
[0039] (3) On the surface covered with the electrode layer and sensor, polymer porous microspheres loaded with drugs are coated on the electrode area with the same charge as the drug on the flexible substrate material. The surface is naturally dried to allow the drug to deposit and form a microsphere drug-loaded layer. A layer of reinforced cellulose paper is laminated on the microsphere drug-loaded layer as a drug protective layer, thus completing the preparation of the scleral contact lens skeleton structure.
[0040] (4) Immerse the scleral contact lens skeleton structure in the gel solution, use DLP equipment to fix and pull it out for printing, and use ultraviolet light to cure it to form a gel covering its surface to build a gel layer until a complete scleral contact lens shape is formed. Then, the gel layer is cut by laser to make through holes, thus obtaining the iontophoresis gel scleral contact lens. When in use, the dual electrodes and pH sensor are connected to the controller to implement iontophoresis drug delivery under the action of electric field.
[0041] An iontophoretic gel scleral contact lens containing a dual-electrode electrode layer was prepared using the above method.
[0042] Example 2:
[0043] An iontophoretic gel scleral contact lens and its preparation method, the method comprising the following steps:
[0044] (1) Take a piece of cellulose paper and immerse it in an acrylamide solution with a mass ratio of methylene bisacrylamide to potassium sulfate of 150:1. Heat it continuously for 6 hours under a nitrogen atmosphere at 60°C. After heating, transfer it to a vacuum drying oven to dry. Once drying is complete, hydrogel-reinforced cellulose paper is obtained. Cut the hydrogel-reinforced cellulose paper to the size that matches the scleral contact lens to obtain a flexible matrix material.
[0045] (2) Take a flexible substrate material and use nano-silver conductive ink to print on its surface to form a single electrode pattern. After sintering at 120°C for 20 minutes, an electrode layer with a single electrode structure is obtained. Protective film tape is applied to the front and back sides, followed by drilling and adding conductive carbon paste (to connect the front and back sides). The working electrode line (WE line), insulating ink, carbon electrode line, Ag / AgCl reference electrode line (RE line), and insulating ink are printed on the front side. Then, the control electrode line (CE line) and insulating ink are printed on the back side. After sintering at 120°C for 20 minutes, a pH sensor is obtained.
[0046] (3) On the surface covered with the electrode layer and sensor, polymer porous microspheres loaded with drugs are coated on the electrode area with the same charge as the drug on the flexible substrate material. The surface is naturally dried to allow the drug to deposit and form a microsphere drug-loaded layer. A layer of reinforced cellulose paper is laminated on the microsphere drug-loaded layer as a drug protective layer, thus completing the preparation of the scleral contact lens skeleton structure.
[0047] (4) The scleral contact lens skeleton structure is immersed in the gel solution, and the DLP device is used to fix and pull it out for printing. The gel is cured by ultraviolet light to form a gel covering its surface, and a gel layer is constructed until a complete scleral contact lens shape is formed. Then, the gel layer is cut by laser to make through holes, thus obtaining the iontophoresis gel scleral contact lens. When in use, the single electrode is connected to the same polarity external power supply, and the counter electrode is attached to the ear or the back of the head, etc., to form an iontophoresis electric field and a pH sensor is connected to the controller to implement iontophoresis drug delivery under the action of the electric field.
[0048] An ion-electroosmotic gel scleral contact lens with a single electrode layer was prepared using the above method.
[0049] Example 3:
[0050] An iontophoretic gel scleral contact lens and its preparation method, the method comprising the following steps:
[0051] (1) Take a piece of cellulose paper and immerse it in an acrylamide solution with a mass ratio of methylene bisacrylamide to potassium sulfate of 150:1. Heat it continuously for 6 hours under a nitrogen atmosphere at 60°C. After heating, transfer it to a vacuum drying oven to dry. Once drying is complete, hydrogel-reinforced cellulose paper is obtained. Cut the hydrogel-reinforced cellulose paper to the size that matches the scleral contact lens to obtain a flexible matrix material.
[0052] (2) Take a flexible substrate material, use nano-silver conductive ink to print a ring-shaped conductive coil on its surface to form a ring-shaped coil pattern, and sinter at 120°C for 20 minutes to obtain an electrode layer with a coil structure. Apply protective film tape to the front and back sides, then drill holes and add conductive carbon paste (to connect the front and back sides). Print the working electrode line (WE line), insulating ink, carbon electrode line, Ag / AgCl reference electrode line (RE line), and insulating ink on the front side. Then print the control electrode line (CE line) and insulating ink on the back side. After sintering at 120°C for 20 minutes, obtain a pH sensor.
[0053] (3) On the surface covered with the electrode layer and sensor, polymer porous microspheres loaded with drugs are coated on the electrode area with the same charge as the drug on the flexible substrate material. The surface is naturally dried to allow the drug to deposit and form a microsphere drug-loaded layer. A layer of reinforced cellulose paper is laminated on the microsphere drug-loaded layer as a drug protective layer, thus completing the preparation of the scleral contact lens skeleton structure.
[0054] (4) The scleral contact lens skeleton structure is immersed in the gel solution, and the DLP device is used to fix and pull it out for printing. The gel is cured by ultraviolet light to form a gel covering its surface, and a gel layer is constructed until a complete scleral contact lens shape is formed. Then, the gel layer is cut by laser to drill through holes, thus obtaining the iontophoresis gel scleral contact lens. A wireless power supply is used to provide an electric field for the drug delivery process on the ring conductive coil to realize iontophoresis drug delivery.
[0055] An ion-electroosmotic gel scleral contact lens containing a ring-shaped conductive coil as an electrode layer was prepared using the above method.
[0056] Example 4:
[0057] An iontophoretic gel scleral contact lens and its preparation method, the method comprising the following steps:
[0058] (1) Take a piece of cellulose paper and immerse it in an acrylamide solution with a mass ratio of methylene bisacrylamide to potassium sulfate of 150:1. Heat it continuously for 6 hours under a nitrogen atmosphere at 60°C. After heating, transfer it to a vacuum drying oven to dry. Once drying is complete, hydrogel-reinforced cellulose paper is obtained. Cut the hydrogel-reinforced cellulose paper to the size that matches the scleral contact lens to obtain a flexible matrix material.
[0059] (2) Take a flexible substrate material and use nano-silver conductive ink to print two electrodes, anode and cathode, on the surface of the substrate to form an electrode pattern. After sintering at 120°C for 20 minutes, an electrode layer is obtained. Protective film tape is applied to the front and back sides, followed by drilling and adding conductive carbon paste (to connect the front and back sides). The working electrode line (WE line), insulating ink, carbon electrode line, Ag / AgCl reference electrode line (RE line), and insulating ink are printed on the front side. Then, the control electrode line (CE line) and insulating ink are printed on the back side. After sintering at 120°C for 20 minutes, a pH sensor is obtained.
[0060] (3) On the surface covered with the electrode layer and sensor, polymer porous microspheres are coated on the electrode area on the flexible substrate material with the same charge as the drug. The microsphere drug-carrying layer is formed by natural drying and deposition on its surface. A layer of reinforced cellulose paper is then laminated on the microsphere drug-carrying layer as a drug protection layer, thus completing the preparation of the scleral contact lens skeleton structure.
[0061] (4) Immerse the scleral contact lens skeleton structure in the gel solution, use DLP equipment to fix and pull it out for printing, and use ultraviolet light to cure it to form a gel covering its surface, build a gel layer until a complete scleral contact lens shape is formed. Then, use laser to cut the gel layer to make through holes, thus obtaining the iontophoresis gel scleral contact lens. When using the iontophoresis gel scleral contact lens, add drug solution through the reserved through holes to achieve controlled and sustained drug release during the drug administration process.
[0062] The above method was used to prepare iontophoresis gel scleral contact lenses for sustainable drug supplementation.
[0063] The iontophoretic gel scleral contact lens prepared in Example 1 was subjected to performance testing. The testing steps are as follows:
[0064] Two equal portions of dexamethasone solution with the same composition were weighed. One portion was applied directly to the eye via passive drug delivery, while the other portion was administered through an iontophoresis gel scleral contact lens with an externally applied current of 5 mA / cm². 2 For ocular iontophoresis drug delivery. Further, by modifying dexamethasone with cationic and anionic forms, passive and iontophoresis drug delivery tests were conducted. The drug concentration in the aqueous humor 2 hours after passive ocular administration and 5 minutes after iontophoresis drug delivery were compared. Figure 5 As shown, the modified iontophoresis drug delivery efficiency was significantly improved.
[0065] Using this method and the iontophoresis gel scleral contact lens prepared by this method, the drug administration is simple and easy, safe and effective, with minimal damage to the eyes. It allows patients to administer the drug themselves, and the drug is delivered directly to the scleral lesion site, avoiding adverse reactions in other tissues or the whole body. It also has a sustained-release function to reduce the frequency of administration.
[0066] The above description is one embodiment provided in conjunction with specific content, and does not imply that the specific implementation of the present invention is limited to these descriptions. Furthermore, due to differences in industry naming conventions, the invention is not limited to the above names or English names. Any methods or structures similar to or identical to those of the present invention, or any technical deductions or substitutions made based on the concept of the present invention, should be considered within the scope of protection of the present invention.
Claims
1. An iontophoresis gel contact lens, characterized by: The contact lens includes a contact lens frame (1), which has a drug-loaded layer (2), an electrode layer (3), and a flexible material (4) covering the electrode layer (3) in sequence from the side closest to the sclera outwards. The contact lens frame (1) is also covered with a gel layer (5). The drug-loaded layer (2) is coated on the electrode layer (3). The drug-loaded layer (2) includes polymer porous microspheres loaded with nano-sustained-release drugs. The preparation method of the iontophoretic gel scleral contact lens includes the following steps: (1) Preparation of flexible materials (4); (2) On the surface of the flexible material (4) obtained in step (1), the corresponding electrode layer (3) on the periphery of the sclera region of the eyeball is printed by inkjet printing with conductive ink and sintered at 100-150℃ for 10-30 min to obtain a flexible material (4) containing the electrode layer (3). (3) Take the flexible material (4) containing the electrode layer (3) obtained in step (2), coat the drug loading layer (2) on the electrode layer (3) of the flexible material (4), and after drying, obtain the contact lens skeleton (1). (4) Immerse the contact lens skeleton (1) in step (3) into the gel solution, and form a gel layer (5) by casting and / or photopolymerization 3D printing to cover its surface, thus obtaining the gel scleral contact lens.
2. The iontophoresis gel scleral contact lens according to claim 1, characterized in that: The drug-loaded layer (2) also includes ionic gelatin nanoparticles or polymer micelles containing drug components.
3. The iontophoresis gel scleral contact lens according to claim 1, characterized in that: The preparation method of the flexible material (4) includes the following steps: immersing the substrate in an acrylamide solution, heating it at 30-90°C for 3-9 hours under a nitrogen atmosphere, removing it, drying it, and cutting it to obtain the flexible material (4).
4. The iontophoresis gel scleral contact lens according to claim 1, characterized in that: The electrode layer (3) is an electrode pattern formed by inkjet printing of conductive ink onto the surface of the flexible material (4) and sintering at low temperature. The electrode layer (3) is located around the sclera region of the eyeball. The contact lens frame (1) also includes a sensor (6) located on the side of the electrode layer (3) near the middle for measuring pH changes during iontophoresis.
5. The iontophoresis gel scleral contact lens according to claim 4, characterized in that: The sensor (6) is prepared by means of the following steps: using a flexible material (4) as a substrate, a protective film tape is applied to its front and back sides, holes are drilled and conductive carbon paste is added to make the front and back sides connected. The working electrode line (WE line), insulating ink, carbon electrode line, Ag / AgCl reference electrode line (RE line), and insulating ink are printed on the front side. Then, the contrast electrode line (CE line) and insulating ink are printed on the back side.
6. The iontophoresis gel scleral contact lens according to claim 1, characterized in that: The gel layer (5) is also provided with a through hole (7) that connects to the outside and the drug-carrying layer (2). The through hole (7) is used for gas discharge and drug addition.
7. The iontophoresis gel scleral contact lens according to claim 1, characterized in that: The drug-carrying layer (2) is further provided with a drug protective layer (20) on the side near the sclera for covering the drug-carrying layer (2).
8. The iontophoresis gel scleral contact lens according to claim 1, characterized in that: In step (2), the metal material in the conductive ink is a metal material with a lower ionization tendency than hydrogen.
9. The iontophoresis gel scleral contact lens according to claim 8, characterized in that: In step (4), the main components of the curing gel during the photocuring 3D printing process include: 2-hydroxyethyl methacrylate, 1-vinyl-2-pyrrolidone, silane coupling agent thermoplastic polyolefin elastomer, polyethylene glycol diacrylate and prepolymer.