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WO-2026097094-A1 - HEMOSTATIC AND SEALANT COMPOSITIONS

WO2026097094A1WO 2026097094 A1WO2026097094 A1WO 2026097094A1WO-2026097094-A1

Abstract

The present disclosure describes hemostatic and sealant compositions glycidyl methacrylated gelatin (GelMAG); methacrylated dopamine (DMA); poly(diallyldimethylammonium chloride) (pDDA); and a visible light-activated photoinitiator. The present disclosure also describes methods of sealing a wound in a tissue of a subject. These methods comprise contacting the wound of the subject with a therapeutically effective amount of the hemostatic and sealant hydrogel precursor composition; and photo-crosslinking the hemostatic and sealant hydrogel precursor composition by exposing the hemostatic and sealant hydrogel precursor composition to a visible light, thereby forming a hemostatic and sealant hydrogel. Methods of preparing hemostatic and sealant hydrogels are also described herein.

Inventors

  • ANNABI, NASIM
  • JAIN, SAUMYA

Assignees

  • REGENTS OF THE UNIVERSITY OF CALIFORNIA

Dates

Publication Date
20260507
Application Date
20251104
Priority Date
20241104

Claims (20)

  1. 1. A hemostatic and sealant composition comprising: glycidyl methacrylated gelatin (GelMAG); methacrylated dopamine (DMA); poly(diallyldimethylammonium chloride) (pDDA); and a visible light-activated photoinitiator.
  2. 2. The hemostatic and sealant composition of claim 1, wherein the DMA is conjugated to a backbone of the GelMAG.
  3. 3. The hemostatic and sealant composition of claims 1 or 2, wherein the GelMAG is present at a concentration of 20% (w/v).
  4. 4. The hemostatic and sealant composition of any one of claims 1-3, wherein the GelMAG is present at a concentration ranging from 15% (w/v) to about 25% (w/v).
  5. 5. The hemostatic and sealant composition of any one of claims 1-4, wherein the DMA is present at a concentration ranging from about 0.05% (w/v) to about 0.15% (w/v).
  6. 6. The hemostatic and sealant composition of claim 5, wherein the DMA is present at a concentration of about 0.1% (w/v).
  7. 7. The hemostatic and sealant composition of any one of claims 1-6, wherein the pDDA is present at a concentration ranging from about 0.5% (v/v) to about 25% (v/v).
  8. 8. The hemostatic and sealant composition of claim 7, wherein the pDDA is present at a concentration of about 2% (v/v).
  9. 9. The hemostatic and sealant composition of any one of claims 1-8, wherein the GelMAG has a degree of methacryloyl substitution of about 50%.
  10. 10. The hemostatic and sealant composition of any one of claims 1-9, wherein the GelMAG has a degree of methacryloyl substitution between about 40% and about 60%. Attorney Docket No. 50835-0006W01
  11. 11. The hemostatic and sealant composition of any one of claims 1-10, wherein the photoinitiator comprises Eosin Y, triethanolamine (TEA), N-vinyl-s-caprolactam (VC), or any combination thereof.
  12. 12. The hemostatic and sealant composition of any one of claims 1-11, wherein the composition is in a form of a solution or a hydrogel.
  13. 13. The hemostatic and sealant composition of any one of claims 1-12, wherein the composition further comprises a pharmaceutically acceptable carrier or excipient.
  14. 14. The hemostatic and sealant composition of any one of claims 1-13, wherein the hemostatic and sealant composition is formulated for topical use.
  15. 15. The hemostatic and sealant composition of any one of claims 1-14, wherein the visible light-activated photoinitiator is activated upon exposure of light having a wavelength between about 450 nanometers (nm) to about 550 nm.
  16. 16. The hemostatic and sealant composition of any one of claims 1-15, wherein the hemostatic and sealant composition is ionically conductive, biocompatible, biodegradable, adhesive, and antibacterial.
  17. 17. A hemostatic and sealant hydrogel precursor composition comprising the hemostatic and sealant composition of any one of claims 1-16.
  18. 18. A hemostatic and sealant hydrogel formed by photo-crosslinking the hemostatic and sealant hydrogel precursor composition of claim 17.
  19. 19. The hemostatic and sealant hydrogel of claim 18, wherein the hemostatic hydrogel has: (i) a Young’s modulus ranging from about 30 kilopascals (kPa) to about 200 kPa; (ii) an ultimate strength ranging from about 60 kPa to about 150 kPa; (iii) a stretchability ranging from about 80% to about 220%; (iv) a toughness of about 20 kilojoules per cubic meter (kJ/m 3 ) to about 105 kJ/m 3 ; (v) a compression modulus of ranging from about 30 kPa to about 80 kPa; (vi) an energy loss of about 10% to about 30%; (vii) an adhesion strength ranging from about 20kPa to about 50 kPa; (viii) an adhesion energy ranging from about 10 joules per cubic meter (J/m 3 ) to about 50 J/m 3 ; (ix) a burst pressure ranging from about 20 kPa to about 60 kPa; (x) a conductivity Attorney Docket No. 50835-0006W01 ranging from about 0.1 Siemens per meter (S/m) to about 1 S/m; or (xi) any combination of (i)-(iv).
  20. 20. A method of sealing a wound in a tissue of a subject, the method comprising: contacting the wound of the subject with a therapeutically effective amount of the hemostatic and sealant hydrogel precursor composition of claim 17; and photo-crosslinking the hemostatic hydrogel precursor composition by exposing the hemostatic hydrogel precursor composition to a visible light, thereby forming a hemostatic hydrogel.

Description

Attorney Docket No. 50835-0006W01 HEMOSTATIC AND SEALANT COMPOSITIONS FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with government support under EB023052 awarded by the National Institutes of Health. The government has certain rights in the invention. TECHNICAL FIELD The present disclosure describes hemostatic compositions comprising photocrosslinkable gelatin-based composite adhesive hydrogels incorporating methacrylated dopamine (DMA) and poly(diallyldimethylammonium chloride) (pDDA). The disclosure also describes methods of sealing a wound in a tissue of a subject in need thereof using the hemostatic compositions and methods of preparing hemostatic hydrogels. BACKGROUND Trauma is one of the top contributors to the global burden of disease, causing more than five million fatalities per year and depleting hundreds of billions of dollars from the world economy. Even in non-fatal injuries, post-traumatic complications (PTCs) are common and awaken serious concerns including coagulopathy, thromboembolism, infection, sepsis, organ failure, and even stroke. Even though medical response to traumatic injuries has improved, numerous obstacles such as excessive blood loss, bacterial infection, and ineffective wound closure hinder patient survival and physiological recovery. Uncontrollable hemorrhage is a leading contributor to preventable mortality after trauma and therefore requires urgent preventative investigation. Hemostasis has traditionally been achieved by compression with gauze or intravenous delivery of blood products, which have their own limitations. For example, gauze provides poor wound treatment due to weak tissue adhesion, high blood adsorption before hemostasis, and fiber shredding into the wound. Secondary bleeding is also common upon clot-filled gauze removal. Even commercial gauzes infused with hemostatic agents such as chitosan (ChitoGauze PRO®), kaolin (QuikClot Combat Gauze®), and zeolites (QuiCover™) have limited tissue adhesion and may cause thrombosis and damage to crucial organs upon extended exposure. Meanwhile, hemostats derived from blood products (e.g., platelets, fibrinogen concentrate) incur risk of thromboembolism and disease transmission. They can also be expensive, have a short shelf life, and involve complex preparation before transfusion. Overall, there are few efficient hemostatic agents currently used to control hemorrhage. Attorney Docket No. 50835-0006W01 Hemostatic biomaterials such as sprays, sponges, and foams have therefore been developed using natural or synthetic polymers reinforced by blood coagulating agents (e.g., tannic acid, graphene oxide, silica particles). These biomaterials topically conform to injuries and trigger blood coagulation, but most lack the mechanical strength and tissue adhesion required for their clinical applications. Thus, there is an urgent medical need to develop hemostatic biomaterials suited for multi-dimensional wound sealing and repair on elastic organs. SUMMARY Certain aspects of the present disclosure are directed to a hemostatic and sealant composition comprising: glycidyl methacrylated gelatin (GelMAG); methacrylated dopamine (DMA); poly(diallyldimethylammonium chloride) (pDDA); and a visible light-activated photoinitiator. In some embodiments, the DMA is conjugated to a backbone of the GelMAG. In some embodiments, the GelMAG is present at a concentration of 20% (w/v). In some embodiments, the GelMAG is present at a concentration ranging from 15% (w/v) to about 25% (w/v). In some embodiments, the DMA is present at a concentration ranging from about 0.05% (w/v) to about 0.15% (w/v). In some embodiments, the DMA is present at a concentration of about 0.1% (w/v). In some embodiments, the pDDA is present at a concentration ranging from about 0.5% (v/v) to about 25% (v/v). In some embodiments, the pDDA is present at a concentration of about 2% (v/v). In some embodiments, the GelMAG has a degree of methacryloyl substitution of about 50%. In some embodiments, the GelMAG has a degree of methacryloyl substitution between about 40% and about 60%. In some embodiments, the photoinitiator comprises Eosin Y, triethanolamine (TEA), N-vinyl-s-caprolactam (VC), or any combination thereof. In some embodiments, the composition is in a form of a solution or a hydrogel. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier or excipient. In some embodiments, the hemostatic and sealant composition is formulated for topical use. In some embodiments, the visible light-activated photoinitiator is activated upon exposure of light having a wavelength between about 450 nanometers (nm) to about 550 nm. In some embodiments, the hemostatic and sealant composition is ionically conductive, biocompatible, biodegradable, adhesive, and antibacterial. Attorney Docket No. 50835-0006W01 In some embodiments, a hemostatic and sealant hydrogel precursor composition comprises any of the previously mentioned hemos