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US-12616652-B2 - Lenses for treating ocular diseases and preparation method thereof

US12616652B2US 12616652 B2US12616652 B2US 12616652B2US-12616652-B2

Abstract

The disclosure provides lenses for treating ocular diseases, including a bowl-shaped silicone hydrogel carrier and umbilical cord mesenchymal stem cells loaded on the carrier; the bowl-shaped silicone hydrogel carrier is polymerized from an organosilicone monomer and a hydrophilic monomer under the action of a cross-linking agent and an initiator; the organosilicone monomer is polymerized from a hydrogenated silicone oil and allyl methacrylate under the action of a polymerization inhibitor and a catalyst; and the umbilical cord mesenchymal stem cells are treated with irradiation.

Inventors

  • Haoyu Zeng
  • Zhenbo Shen
  • Yuanyue Liu
  • Tian Guan
  • Jiexing Chen

Assignees

  • GUANGDONG PROCAPZOOM BIOSCIENCES CO., LTD.

Dates

Publication Date
20260505
Application Date
20221229

Claims (15)

  1. 1 . Lenses for treating ocular diseases, comprising a bowl-shaped silicone hydrogel carrier and umbilical cord mesenchymal stem cells loaded on the carrier; wherein the bowl-shaped silicone hydrogel carrier is polymerized from an organosilicone monomer and a hydrophilic monomer under an action of a cross-linking agent and an initiator; the organosilicone monomer is polymerized from a hydrogenated silicone oil and allyl methacrylate under the action of a polymerization inhibitor and a catalyst; and the umbilical cord mesenchymal stem cells are treated with irradiation.
  2. 2 . The lenses for treating ocular diseases of claim 1 , wherein the hydrophilic monomer is a mixture of hydroxyethyl methacrylate, N-vinylpyrrolidone and N-methyl-N-vinylacetamide.
  3. 3 . The lenses for treating ocular disease of claim 2 , wherein the cross-linking agent is ethylene glycol dimethacrylate, and wherein the initiator is azobisisobutyronitrile.
  4. 4 . The lenses for treating ocular diseases of claim 3 , wherein a weight ratio of the organosilicone monomer to the hydrophilic monomer to the cross-linking agent to the initiator is (25˜30):(55˜60):(0.6˜0.8):(0.4˜0.6).
  5. 5 . The lenses for treating ocular diseases of claim 1 , wherein the polymerization inhibitor is hydroquinone, and the catalyst is chloroplatinic acid.
  6. 6 . The lens for treating ocular diseases of claim 5 , wherein a weight ratio of the hydrogenated silicone oil to allyl methacrylate to the polymerization inhibitor to the catalyst is (500˜520):(34˜35):(0.02˜0.04):(0.06˜0.08).
  7. 7 . The lenses for treating ocular diseases of claim 1 , wherein the bowl-shaped silicone hydrogel carrier has a diameter of 12˜15 mm, a radius of curvature of 8.3˜8.6 mm, a center thickness of 0.07˜0.09 mm, and an oxygen permeability of 135 DK/t or above.
  8. 8 . The lenses for treating ocular diseases of claim 1 , wherein a circular blank area without the umbilical cord mesenchymal stem cells is disposed in a middle of the bowl-shaped silicone hydrogel carrier, and the circular blank area has a diameter of 2˜6 mm.
  9. 9 . The lenses for treating ocular diseases of claim 1 , wherein a quantity of the umbilical cord mesenchymal stem cells loaded on the carrier is 1.0˜2.0×10 5 .
  10. 10 . A preparation method of lenses for treating ocular diseases, comprising steps as follows: 1) culturing and expanding umbilical cord mesenchymal stem cells with a complete medium; 2) adding a complete medium into a culture dish, putting a bowl-shaped silicone hydrogel carrier in the culture dish upside down, and incubating the bowl-shaped silicone hydrogel carrier in an incubator at 30-40° ° C. for 0.5-2 h; 3) taking another new culture dish, adding the complete medium into the new culture dish, taking out the silicone hydrogel carrier incubated in step 2), and placing the silicone hydrogel carrier vertically into the complete medium, with a bowl mouth facing up; 4) dissociating the umbilical cord mesenchymal stem cells cultured in step 1), performing resuspension uniformly, dripping an absorbed cell suspension into a concave surface of the bowl-shaped silicone hydrogel carrier, and placing the cells into an incubator for culture after the cells are settled; 5) performing periodic washing and exchange of the complete medium, performing washing after the umbilical cord mesenchymal stem cells overspread the silicone hydrogel carrier, transferring the silicone hydrogel carrier to a lenses access box filled with the complete medium, and sealing the silicone hydrogel carrier with a sealing film; and 6) irradiating the sealed bowl-shaped silicone hydrogel carrier to obtain lenses; wherein the bowl-shaped silicone hydrogel carrier is polymerized from an organosilicone monomer and a hydrophilic monomer under an action of a cross-linking agent and an initiator; the silicone monomer is polymerized from hydrogenated silicone oil and allyl methacrylate by a polymerization inhibitor and a catalyst.
  11. 11 . The preparation method of the lenses for treating ocular diseases of claim 9 , wherein a preparation method of the organosilicone monomer is as follows: mixing hydrogenated silicone oil, allyl methacrylate, a solvent and a polymerization inhibitor in a solvent uniformly, performing heating under inert atmosphere, adding a catalyst, performing a reaction, and performing distillation under reduced pressure after completion of the reaction to produce the silicone monomer.
  12. 12 . The preparation method of the lenses for treating ocular diseases of claim 9 , wherein a preparation method of the bowl-shaped silicone hydrogel carrier is as follows: mixing an organo-siloxane monomer, a hydrophilic monomer, an initiator and a cross-linking agent in a solvent to obtain a mixed solution, filling a plastic mold with the mixed solution, introducing nitrogen, performing heat curing, lathing a polymer rod obtained after curing to be of a button shape, and finally cutting the button-shaped material on two sides to produce the bowl-shaped silicone hydrogel carrier.
  13. 13 . A method of the lenses of claim 1 in treatment of the chronic ocular graft-versus-host disease.
  14. 14 . A method of the lenses of claim 1 in treatment of Mooren's corneal ulcer.
  15. 15 . A method of the lenses of claim 1 in inhibition of post-keratoplasty rejection.

Description

FIELD The present disclosure belongs to the field of biotechnology, in particular to lenses for treating ocular diseases and a preparation method thereof. BACKGROUND Chronic ocular graft-versus-host disease (oGVHD) is caused by allogeneic hematopoietic stem cell transplantation (allo-HSCT), results from an imbalance in the protective immune mechanism and inflammatory mechanism of the ocular surface, which is essentially that donor's T cells attack recipient's eye tissues including the fibroblasts of the recipient's lacrimal duct, which makes the lacrimal duct fibrotic, severely affecting the secretory function of the lacrimal gland. The clinical manifestations of oGVHD are mainly ocular surface inflammation, dry eye and corneal ulcer, which in severe cases can lead to a series of complications threatening visual function and ocular health, such as corneal perforation and atretoblepharia. Thus, oGVHD severely affects the vision and the quality of life of a patient, and often results in vision loss of the patient if not diagnosed early and properly treated. A strategy to treat oGVHD is to prevent overactive donor's T cells from attacking recipient's lacrimal duct and other eye tissues. There is no specific drug for the treatment of oGVHD at current. The three drugs (imbruvica, belumosudil and ruxolitinib) approved by FDA to treat chronic graft-versus-host disease are not targeted at oGVHD and cannot alleviate the symptoms of oGVHD. Current treatment solutions for oGVHD include systemic administrations, topical treatments, and surgical treatments. The systemic administrations commonly use steroid hormones or combined calcineurin inhibitors/immunosuppressants (e.g., cyclosporine and tacrolimus), but systemic administration is difficult to achieve effective drug concentrations in the eye, has negative impact on the therapeutic effect of allo-HSCT, and easily causes infection. The topical treatments mainly include artificial tears (limitations: corneal calcification caused by long-term use), ophthalmic lubricants (limitations: existence of preservatives, which in turn cause additional problems), topical immunosuppressants (limitations: incapability of reversing the damage that has occurred), autologous serum eye drops (limitations: high cost, difficulty in preservation, and easiness in contamination), lacrimal punctum embolism (disadvantages: prolong the time that inflammatory factors remain in the tears to worsen the disease course), and wearing contact lenses (disadvantages: aggravation of local inflammation in the absence of tears). For severe cases, tarsorrhaphy may be performed (shortcomings: incapability of excluding intraocular secretions normally to result in ocular infections). The above three solutions cannot prevent/repair corneal scarring and have limited application and efficacy. Therefore, the key to treat oGVHD is local prevention of attack of hyperactive donor's T cells on recipient's lacrimal duct and other eye tissues. Umbilical Cord Mesenchymal Stem Cells (UCMSCs) have unique immunomodulatory effects: by secreting soluble cytokines, regulating the release of multiple anti-inflammatory factors, inhibiting the proliferative response of T cells when T cells are stimulated by alloantigens, thereby allowing the body to acquire immunological tolerance, and maintaining immunological homeostasis. Indoleamine 2,3-dioxygenase (IDO) secreted by UCMSCs play a major role in inhibiting the proliferative response of T cells by UCMSCs: by stimulation of interferon γ (IFN-γ), UCMSCs secrete IDO that degrades tryptophan to produce kynurenine, which in turn inhibits proliferation of T cells and promotes the apoptosis of T cells. UCMSCs can also promote the proliferation and activation of regulatory T cell (Treg cells) and inhibit the proliferation and activation of a subset of pro-inflammatory T helper cells (including Th1 and Th17 cells) so as to inhibit expressions of pro-inflammatory cytokines TNF-α, IFN-γ. IL-6, and IL-23, and can promotes expression of the anti-inflammatory factors IL-4, and inhibits expressions of the metalloproteinases MMP1, MMP2 and MMP9, so as to reduce inflammatory damage in the body and maintain self-tolerance of the body, and promote the body to switch from an inflammatory environment to an anti-inflammatory environment to induce immunological tolerance. Thus, the immunomodulatory role of UCMSCs offers the potential for their use in the clinical treatment of oGVHD. UCMSCs are used in a variety of methods internally, externally, systemically, and topically. oGVHD requires a topically external treatment method because intravenous or local injection of UCMSC into the body interferes with or affects the therapeutic effect of allo-HSCT. Whereas topically external UCMSCs can only inhibit the attack of donor's T cells on recipient's lacrimal duct and other eye tissues at the ocular surface without affecting the normal function of the donor's T cells as desired elsewhere in the body. However,