Soluble riboflavin microneedle patch
By loading perfluoronaphthane nanoemulsion into soluble riboflavin microneedle patches, riboflavin penetration is promoted and oxygen is released into the corneal stroma, which solves the problems of insufficient penetration and oxygen supply in corneal ectasia, achieving better cross-linking effect and reducing corneal damage.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-07
- Publication Date
- 2026-04-14
AI Technical Summary
Among the existing treatments for corneal ectasia, riboflavin penetration is poor and oxygen supply is insufficient, resulting in unsatisfactory cross-linking effects, and conventional methods cause significant damage to the cornea.
A soluble riboflavin microneedle patch is used, loaded with perfluoronaphthalene nanoemulsion, which forms micropores to promote riboflavin penetration and release oxygen in the corneal stroma, reducing damage to the cornea.
It increased the penetration of riboflavin into the corneal stroma, enhanced the cross-linking effect, and reduced corneal damage, allowing micro-wounds to heal within 12 hours.
Smart Images
Figure CN224113026U_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of medical devices, and more specifically, to an oxidized riboflavin microneedles (O2RF@MNs). Background Technology
[0002] The incidence of corneal ectasia is approximately 1 / 2000-1 / 2500. Clinically, it manifests as early progressive refractive errors, increased irregular astigmatism, and decreased corrected visual acuity. In later stages, it progresses to rupture of the posterior elastic lamina, scarring, and even perforation. Ultimately, 15-20% of patients require deep lamellar or penetrating keratoplasty. Corneal collagen cross-linking is currently the most effective method to prevent or delay the progression of corneal ectasia and has been widely used to treat progressive keratoconus and surgery-related corneal ectasia. However, this response is oxygen-dependent. During cross-linking, oxygen levels in the corneal stroma drop rapidly within 10 to 15 seconds after UV irradiation, and it takes at least 3-4 minutes for oxygen to return to its original level. In a hypoxic environment, cross-linking does not strengthen the cornea. Currently, some studies use goggles, eyelid speculum, face masks, or pulsed light therapy during UV irradiation to increase oxygen supply, finding that these can significantly enhance the effectiveness of cross-linking. However, these methods require additional oxygen supply devices, increasing the complexity of the procedure.
[0003] Currently, commonly used corneal cross-linking methods include ablation corneal collagen cross-linking surgery and transepithelial corneal collagen cross-linking surgery. (1) Ablation corneal collagen cross-linking surgery (Dresden protocol): Before treatment, corneal epithelium with a diameter of 8 mm is removed, and 0.1% riboflavin-5'-monophosphate sodium salt (RF) solution is applied to the debrided corneal center for 30 minutes to allow RF to fully penetrate into the corneal stroma. Then, 3 mw / cm 2 Expose the cornea to ultraviolet light for 30 minutes or 9 mw / cm 2 (1) The cornea is irradiated with ultraviolet light for 10 minutes, but because the corneal epithelium needs to be removed, the damage is greater, and the postoperative pain is obvious, and the incidence of corneal opacity and infection is high. (2) Transepithelial corneal collagen cross-linking surgery is performed while preserving the corneal epithelium. By adding penetration enhancers such as benzalkonium chloride, tromethamine, and ethylenediaminetetraacetic acid to the RF preparation, the penetration of the drug into the corneal epithelium is enhanced. However, in clinical practice, most of these preparations have weak penetration effects, less RF enters the corneal stroma, and the cross-linking effect is poor. It cannot achieve the effect of the classic epithelial removal therapy. A considerable number of patients have experienced the progression of corneal ectasia after transepithelial cross-linking therapy.
[0004] Therefore, there is a need to develop a soluble riboflavin microneedle patch for the treatment of corneal ectasia. Summary of the Invention
[0005] The purpose of this invention is to provide a soluble riboflavin microneedle patch for treating corneal ectasia. The soluble riboflavin microneedle patch is used to improve the amount of RF penetrating into the corneal stroma and increase the oxygen supply during the corneal cross-linking process, thereby enhancing the cross-linking effect in corneal ectasia.
[0006] The soluble riboflavin microneedle patch of this application can form reversible micropores in the corneal epithelium, overcoming the barrier effect of the hydrophobic corneal epithelium on hydrophilic radioactive radium (RF) and promoting RF penetration. Simultaneously, the soluble riboflavin microneedle patch is loaded with an oxygen-releasing nanoemulsion (O2NE). Perfluorodecalin (PFD), due to the low polarity of fluorine, can bind and store oxygen. After the microneedles dissolve, O2NE permeates into the corneal stroma, continuously releasing oxygen within it. During the cross-linking process, no additional oxygen supply device is needed, thereby enhancing the corneal cross-linking effect. Furthermore, the tiny wounds created by the microneedles on the corneal epithelium can heal completely within 12 hours, resulting in minimal corneal damage.
[0007] To achieve the above-mentioned objectives, this application adopts the following technical solution:
[0008] This application provides a soluble riboflavin microneedle patch, the soluble riboflavin microneedle patch including a patch base and a needle array disposed on the patch base, the needle array including a plurality of microneedles.
[0009] Furthermore, the microneedles are loaded with perfluoronaphthane nanoemulsion particles.
[0010] Furthermore, the diameter of the perfluoronaphthalene nanoemulsion particles is 100-300 nm.
[0011] Furthermore, the soluble riboflavin microneedle patch consists of a 14×14 needle array.
[0012] Furthermore, the patch base is 1cm long, 1cm wide, and has a base thickness of approximately 100μm.
[0013] Furthermore, the microneedle has a conical shape, a height of approximately 550 μm, a bottom width of approximately 320 μm, and a distance of approximately 340 μm between the microneedles.
[0014] In summary, this application has the following beneficial effects:
[0015] 1. Excellent RF penetration: After O2RF@MNs delivery, the drug content in the corneal stroma exceeds that of classic deepithelial therapy and commercial transepithelial formulation Peschek TE;
[0016] 2. Minimal corneal damage: O2RF@MNs causes corneal epithelial damage that can be fully recovered within 12 hours, while corneal epithelial damage caused by classic epithelial depigmentation therapy takes 72 hours to fully recover.
[0017] 3. O2RF@MNs can release oxygen in the corneal stroma, increasing the amount of oxygen in the corneal stroma and the overall crosslinking effect during ultraviolet light crosslinking. Attached Figure Description
[0018] Figure 1 Scanning electron microscope (SEM) images of RF@MNs and O2RF@MNs. (A) SEM image of RF@MNs; (B) SEM image of O2RF@MNs.
[0019] Figure 2 Slit-lamp microscopy images of O2RF@MNs and transparent microneedle patches. (A) Slit-lamp microscopy image of O2RF@MNs; (B) Slit-lamp microscopy image of transparent microneedle patches.
[0020] Figure 3 Confocal and inverted fluorescence microscopy images of O2RF@MNs. (A) Side and top views of O2RF@MNs observed using 3D mode of laser confocal microscopy. (B) Images of O2RF@MNs observed under bright field and (C) blue light excitation by inverted fluorescence microscopy. Detailed Implementation
[0021] The technical solutions and effects of this application will be further described in detail below with reference to the embodiments and accompanying drawings. It should be understood that the specific embodiments described herein are merely for explaining the invention and are not intended to limit the invention.
[0022] Example
[0023] The oxygen-releasing riboflavin microneedle patch of this embodiment consists of a 14 × 14 needle array. The patch is 1 cm long and 1 cm wide, with a base thickness of approximately 100 μm. The needles are conical in shape, with a needle height of approximately 550 μm, a base width of approximately 320 μm, and a spacing of approximately 340 μm between the needles. The perfluoronaphthane nanoemulsion particles loaded within the microneedles have a diameter of approximately 100-300 nm.
[0024] The oxygen-releasing riboflavin microneedle patch is prepared by the following steps:
[0025] The O2RF@MNs in this embodiment consists of a 14 × 14 needle array. The patch is 1 cm long and 1 cm wide. The thickness of the microneedle patch base is about 100 μm. The needles are conical in shape, with a needle height of about 550 μm, a needle base width of about 320 μm, and a spacing of about 340 μm between the needles. The diameter of the O2NE loaded in the microneedles is about 100-300 nm.
[0026] The oxygen-releasing O2RF@MNs are prepared by the following steps:
[0027] Step 1: Preparation of O2NE:
[0028] Water, PFD, and fatty alcohol polyoxyethylene ether were mixed in a ratio of 14:5:1 (w / w) and then sonicated in an ice-water bath for 5 minutes to form a perfluoronaphthalene nanoemulsion. The perfluoronaphthalene nanoemulsion was then oxygenated in a hyperbaric oxygen chamber to form O2NE. The oxygenated O2NE was stored in a sealed glass bottle until further use.
[0029] Step 2: Preparation of O2RF@MNs:
[0030] Dissolve 20 mg HA and 3 mg RF (adjusted to 1-5 mg depending on the drug loading of the microneedles) in 1 mL of ultrapure water. Dissolve 6 mg PLA in 0.15 mL of acetone, then vortex to dissolve. Add the 1 mL PLA-HA solution mixture containing 100 μL O2NE to a PDMS mold, then dry in a vacuum oven at 37°C overnight. After drying, carefully remove the O2RF@MNs from the PDMS mold and visually inspect their mechanical strength and homogeneity. Store the O2RF@MNs in oxygen-enriched packaging and protect from light until use.
[0031] In addition, this embodiment also prepared RF@MNs that cannot release oxygen, and the preparation method is as follows:
[0032] Dissolve 20 mg HA and 3 mg RF (adjusted to 1-5 mg depending on the drug loading of the microneedles) in 1 mL of ultrapure water. Dissolve 6 mg PLA in 0.15 mL of acetone and then vortex to dissolve. Add 1 mL of the PLA-HA solution mixture to a PDMS mold and then dry it overnight in a vacuum oven at 37°C. After drying, carefully remove the RF@MNs from the PDMS mold and visually inspect their mechanical strength and homogeneity.
[0033] Scanning electron microscopy observation of the morphology and structure of RF@MNs and O2RF@MNs
[0034] The morphology and structure of RF@MNs and O2RF@MNs were characterized using scanning electron microscopy. The accelerating voltage was set to 2.50 kV, the working distance was 4.8-8.0 mm, and the imaging was performed in SE2 signal mode.
[0035] Please refer to the appendix. Figure 1 The morphological structure of O2RF@MNs and O2RF@MNs was shown. The results showed that both types of microneedles were uniformly arranged in a conical shape. The surface of RF@MNs without O2NE was smoother, while the surface of O2RF@MNs with O2NE was rougher, which may be due to the attached O2NE.
[0036] Characterization of microneedle morphology using slit-lamp microscopy
[0037] First, use micro-tweezers to hold the microneedle sample in front of the lens, adjust the slit-lamp microscope until the microneedles are clearly observed, and obtain front and side views of the microneedle array.
[0038] Please refer to the appendix. Figure 2 The morphology of O2RF@MNs and transparent microneedles under a slit-lamp microscope was shown. The results showed that the microneedle patch was 1 cm long and 1 cm wide, and both microneedle arrays were arranged in a 14 × 14 pattern with conical needle tips. O2RF@MNs appeared yellow, while the blank microneedles without RF loading remained transparent.
[0039] Microneedle morphology characterization using confocal laser scanning microscopy and inverted fluorescence microscopy
[0040] Morphological characterization of O2RF@MNs was performed using 3D imaging mode of confocal laser scanning microscopy and inverted fluorescence microscopy. First, O2RF@MNs were fixed onto a glass slide using nano-adhesive for physical fixation to ensure imaging stability. Continuous tomographic scanning along the Z-axis was performed using either inverted fluorescence microscopy or 3D imaging mode of confocal laser scanning microscopy.
[0041] Please refer to the appendix. Figure 3 The morphology and drug loading of O2RF@MNs were shown. The results showed that O2RF@MNs appeared green under blue light excitation and were loaded with a large amount of RF in the needle, which can serve as a drug reservoir for corneal cross-linking.
[0042] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.
Claims
1. A soluble riboflavin microneedle patch, characterized in that, The soluble riboflavin microneedle patch includes a patch base and a needle array disposed on the patch base, the needle array including multiple microneedles; The microneedles are loaded with perfluoronaphthane nanoemulsion particles; The diameter of the perfluoronaphthalene nanoemulsion particles is 100-300 nm.
2. The soluble riboflavin microneedle patch according to claim 1, characterized in that, The soluble riboflavin microneedle patch consists of a 14×14 needle array.
3. The soluble riboflavin microneedle patch according to claim 1, characterized in that, The patch base is 1cm long, 1cm wide, and has a base thickness of approximately 100μm.
4. The soluble riboflavin microneedle patch according to claim 1, characterized in that, The microneedle has a conical shape, a height of approximately 550 μm, a bottom width of approximately 320 μm, and a distance of approximately 340 μm between the microneedles.