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US-12622997-B2 - Method for treating active bleeding using biocompatible hemostatic and sealant compositions

US12622997B2US 12622997 B2US12622997 B2US 12622997B2US-12622997-B2

Abstract

The present specification describes a biocompatible hemostatic composition and a biocompatible tissue sealant, which when used in combination provides a safe and effective method of achieving hemostasis. The biocompatible composition and sealant may be applied either on a surface of the patient's body, or inside the body cavity. The combination may be used to control bleeding from external wounds and internal injuries, as well as to minimize bleeding during surgical procedures.

Inventors

  • Xin Ji
  • Xueshen Shi
  • Xiaoguang Zhang

Assignees

  • BEIJING UNIVERSAL LIKANG TECHNOLOGY CO., LTD.

Dates

Publication Date
20260512
Application Date
20240424
Priority Date
20180112

Claims (17)

  1. 1 . A method of using a combination of a biocompatible modified starch hemostatic product and a biocompatible sealant gel to treat a bleeding wound within or on a mammal, comprising: applying a first amount of said biocompatible modified starch hemostatic product to said bleeding wound; waiting for a first period of time to permit the biocompatible modified starch hemostatic product to hydrate and adhere to the wound and form a first absorbent layer on the wound surface; and, applying a second amount of said biocompatible sealant gel to the bleeding wound, after formation of the first absorbent layer, wherein the biocompatible sealant gel comprises a material different from the biocompatible modified starch hemostatic product and is adapted to gelatinize in less than three minutes upon contact with the wound and to form a second sealing layer over the first absorbent layer and wherein said first amount and said second amount in combination are sufficient to cause at least one of: hemostasis in said bleeding wound, wound sealing in said wound, reducing exudation of said bleeding wound, promoting tissue healing of said wound, protecting a surface of said wound, and avoiding infection of said wound.
  2. 2 . The method of claim 1 , wherein said biocompatible modified starch hemostatic product comprises at least one of a carboxymethyl starch (CMS) hemostatic powder, pre-gelatinized modified starch hemostatic powder, gelatinized modified starch hemostatic powder, and a crosslinked carboxymethyl starch (CMS) hemostatic powder.
  3. 3 . The method of claim 1 , wherein said biocompatible sealant gel is a biocompatible modified starch gel.
  4. 4 . The method of claim 1 , wherein particle sizes of said biocompatible modified starch hemostatic powder ranges from 1-1000 micrometers, the biocompatible modified starch hemostatic powder has a molecular weight ranging from 1500-250000 Daltons, and the biocompatible modified starch hemostatic powder has a water absorbency capacity greater than or equal to 12 ml/g.
  5. 5 . The method of claim 1 , wherein the biocompatible sealing gel comprises a combination of pentanedioic acid bis-(2,5-dioxo-pyrrolidin-1-yl) ester and a thiol terminated poly(ethylene glycol) polymer.
  6. 6 . The method of claim 1 , further comprising applying the biocompatible sealant gel on top of the biocompatible modified starch hemostatic product.
  7. 7 . The method of claim 1 , further comprising repeating said application of the first amount and the second amount until complete hemostasis is achieved.
  8. 8 . The method of claim 1 , further comprising delaying said application of the biocompatible sealant gel after applying the biocompatible modified starch hemostatic product.
  9. 9 . The method of claim 1 , wherein said biocompatible sealant gel is adapted to gelatinize in approximately less than 3 minutes upon contact with the bleeding wound.
  10. 10 . The method of claim 1 , wherein the biocompatible sealant gel comprises a combination of natural hemostatic polysaccharide and synthetic hemostatic glue.
  11. 11 . The method of claim 10 , wherein the natural hemostatic polysaccharide comprises at least one of a biocompatible modified starch gel, a biocompatible modified starch glue, a cellulose glue and a fibrin glue.
  12. 12 . The method of claim 10 , wherein the synthetic hemostatic glue comprises at least one of hyaluronic acid (HA) gel, hyaluronic acid (HA) glue, polyethylene glycol (PEG) glue, polyethylene oxide (PEO) glue, synthetic polymer glue, and synthetic polymer gel.
  13. 13 . The method of claim 1 , wherein the bleeding wound is located in at least one of the mammal's respiratory tract, digestive tract, genital tract, and gastrointestinal tract.
  14. 14 . The method of claim 1 , wherein the biocompatible sealant gel comprises one or more of a sugar, a polymeric compound, and a protein.
  15. 15 . The method of claim 14 , wherein the sugar is at least one of a Pullulan polysaccharide, maltose, pre-gelatinized starch, Dextran, hydroxypropyl distarch phosphate, sodium carboxymethyl starch, crosslinked CMS, hydroxyethyl starch, oxidized starch, and grafted starch.
  16. 16 . The method of 14 , wherein the polymeric compound is at least one of N-butyl cyanoacrylate, polyethylene glycol/polyethylene oxide (PEG/PEO), polyvinyl acetate (PVA), and polyvinylpyrrolidone (PVP).
  17. 17 . The method of claim 1 , wherein the biocompatible sealant gel comprises two of fibrin glue, bio-glue, a polyethylene glycol (PEG) and PEG combination, carboxymethyl starch (CMS) and glycerol in combination with 5% polyvinyl acetate (PVA) solution, CMS and soybean oil in combination with 5% PVA solution, and CMS and glycerol in combination with 5% hydroxypropyl distarch phosphate (HPDSP).

Description

CROSS-REFERENCE The present application is a continuation application of U.S. patent application Ser. No. 16/959,994, titled “Method for Treating Active Bleeding by Sequentially Applying a Biocompatible Hemostatic Composition and a Sealant Composition” and filed on Jul. 2, 2020, which is a National Stage application of PCT Application Number PCT/CN2019/071108 under 35 U.S.C. 371, which, in turn, claims the benefit of, and priority to, Chinese Patent Application Number 201810031082.4, filed on Jan. 12, 2018. All of the above applications are hereby incorporated by reference in their entirety. FIELD The present specification relates generally to hemostasis and sealing of tissue, and more specifically, to a method that uses biocompatible materials to achieve the functions of hemostasis as well as surgical sealing to control bleeding from a tissue. BACKGROUND Surgical operations and trauma may create bleeding wounds, which can bring a risk of excess blood loss. In such situations therefore, it is necessary to apply hemostats to control bleeding in a timely manner. It is common to apply biocompatible, absorbable hemostatic agents directly to bleeding wound sites to achieve hemostasis (cessation of bleeding) in surgical procedures, trauma treatment and home self-rescue. Products commonly used for treating wounds include tissue sealants and hemostats, such as hemostatic powders and dressings including bandages, hemostatic sponges, and gauzes. Tissue sealants function by solidifying or gelatinizing (gel forming) and/or by interacting with blood to trigger clot formation. Sealants are effective when there is mild bleeding or oozing, such as from a capillary or small vein, in cases of low outflow of blood extruding from a tissue, or as surgical adhesive to seal a tissue after operation. However, when the bleeding is profuse or active, the efficacy of sealants is significantly reduced, as the heavy outflow of blood washes away the sealant gel or glue before it is able to set in at the site and start functioning. Hemostats such as powders, sponges or gauzes are useful to control the bleeding if it is mild to moderate. However, profuse bleeding requires use of other techniques such as manual (topical) compression in addition to hemostats to achieve cessation of bleeding. For example, U.S. Pat. No. 8,912,168, assigned to Xin Ji, discloses hemostat and sealant products based on modified starch. However, one of the main disadvantages of modified starch based compositions is that the gel formed at the site of application is not strong enough to hold when the flow of blood is high. This is because modified starch alone cannot covalently bond to tissue proteins, and is therefore unsatisfactory as a sealant and shows poor efficacy in case of profuse bleeding. U.S. Pat. Nos. 5,874,500 and 6,312,725, both assigned to Cohesion Technologies, dis close polyethylene glycol (PEG) and fibrin glue based sealant compositions. PEG and fibrin glue both have the capability of forming cross links with tissue proteins at the site of bleeding. However, both PEG and fibrin glue work ideally on sealing oozing wounds (exhibiting mild bleeding) or on wounds which are dry (bleeding has stopped). For PEG based compositions, gel forming takes some time so when there is active bleeding the blood tends to wash away the applied composition before it is able to form a gel and set in to seal the wound. In general, a clinician needs to use both a hemostat and a sealant to treat the wound when there is active bleeding, especially when bleeding is accompanied by internal injury or trauma, or needs to be minimized during a surgical procedure. Doctors also frequently need to use surgical sealants within “wet” wounds when there is bleeding and/or extrudates are coming out from the wounds. There is therefore a need for a product which provides the functions of both hemostasis and wound sealing in an effective and timely manner, even when the bleeding is profuse. Further, the product should be convenient to use and capable of being applied topically on a bleeding wound surface outside or within the body cavity. Such a hemostatic product must be capable of being applied directly or by means of ancillary devices, such as a specific delivery device or endoscope, so as to achieve rapid and effective hemostasis, seal the wound and avoid re-bleeding. SUMMARY In some embodiments, the present specification discloses a method of using a combination of a biocompatible hemostatic product and a biocompatible sealant product to treat a bleeding wound within or on a mammal, comprising: applying a first amount of said biocompatible hemostatic product to said bleeding wound; applying a second amount of said biocompatible sealant product to the bleeding wound, wherein said first amount and said second amount in combination are sufficient to cause at least one of: hemostasis in said bleeding wound, wound sealing in said wound, reducing exudation of said bleeding wound, promoting