Hemostatic devices with improved properties and methods of making same
Hemostatic devices and methods of making same are disclosed. Disclosed hemostatic devices include biocompatible non-oxidized regenerated cellulose. The disclosed hemostatic devices are effective in providing and maintaining hemostasis in cases of moderate to severe bleeding caused by non-compressional and/or non-tourniquetable injuries, among other things. The disclosed methods enable manufacture of a bioabsorbable, biocompatible, biodegradable carboxymethyl cellulose having high stability and high adherence.
1. A method of making non-oxidized, non-regenerated sodium carboxymethyl cellulose (Na-CMC) comprising:
alkali treating non-oxidized, non-regenerated Na-CMC by exposing the non-oxidized, non-regenerated Na-CMC to an alkalization agent solution at a first temperature, wherein the alkalization agent solution comprises an alkalization agent, water, and an organic solvent;
forming an acid solution comprising a monohaloacetic acid;
forming a saturated solution comprising the alkali-treated non-oxidized, non-regenerated Na-CMC, the alkalization solution, and the acid solution, wherein the saturated solution further comprises sedimentary salt, and has a water to organic solvent ratio up to about 22%;
dissolving the sedimentary salt by mixing the saturation solution at a second temperature of about 40° C. to about 60° C. for about four hours to about seven hours to form an etherification solution, wherein the second temperature is higher than the first temperature; and
forming the non-oxidized, non-regenerated Na-CMC in the saturated solution for about two to about twenty four hours at a temperature of about 40° C. to about 60° C., wherein the saturated solution has a water to ethanol ratio up to about 22%.
2. The method of claim 1 , wherein the first temperature is room temperature and the second temperature is from about 40° C. to about 60° C.
3. The method of claim 2 , wherein the saturated solution is mixed at a temperature of about 50° C.
4. The method of claim 1 , wherein the saturated solution is mixed for about four hours.
5. The method of claim 1 , wherein the non-oxidized, non-regenerated Na-CMC is biocompatible, water-soluble, water-swellable, or a combination thereof.
6. The method of claim 1 , wherein the non-oxidized cellulose is amorphous, crystalline or a combination thereof.
7. The method of claim 1 , wherein the organic solvent is selected from the group consisting of ethanol, toluene, acetone, 2-propanol or a mixture thereof.
8. The method of claim 7 , wherein the organic solvent is ethanol.
9. The method of claim 1 , wherein the alkalization agent is selected from the group consisting of sodium hydroxide (NaOH), potassium hydroxide (KOH), calcium hydroxide (Ca(OH) 2 ), or a mixture thereof.
10. The method of claim 1 , wherein alkalization solution comprises about 11% w/w NaOH solution, about 21% water, and about 68% ethanol.
11. The method of claim 1 , wherein the monohaloacetic acid is chloroacetic acid.
12. The method of claim 11 , wherein the monohaloacetic acid is sodium monochloroacetic acid (ClCH 2 COON a ).
13. The method of claim 1 , wherein the level of carboxymethyl group substitution of the Na-CMC is about 0.88.
14. A hemostatic device, comprising:
non-oxidized, non-regenerated sodium carboxymethyl cellulose (Na-CMC) having a level of carboxymethyl group substitution of about 0.88; wherein:
the non-oxidized, non-regenerated Na-CMC forms a hemodynamic gel when it contacts blood, wherein the Na-CMC is formed by a process comprising:
an alkali treatment comprising exposing the non-oxidized, non-regenerated Na-CMC to an alkalization agent solution at a first temperature, wherein the alkalization agent solution comprises an alkalization agent, water, and an organic solvent;
forming an acid solution comprising a monohaloacetic acid;
forming a saturated solution comprising the alkali-treated non-oxidized, non-regenerated cellulose, the alkalization agent solution, and the acid solution, wherein the saturated solution comprises sedimentary salt, and has a water to ethanol ratio up to about 22%;
dissolving the sedimentary salt by mixing the saturated solution at a second temperature of about 40° C. to about 60° C. for about four hours to about seven hours to form a solution for etherification, wherein the second temperature is higher than the first temperature; and
forming the non-oxidized, non-regenerated Na-CMC in the saturated solution for about two to about twenty four hours at a temperature of about 40° C. to about 60° C., the saturated solution having a water to ethanol ratio up to about 22%.
15. The hemostatic device of claim 14 , wherein the first temperature is room temperature and the second temperature is from about 40° C. to about 60° C.
16. The hemostatic device of claim 14 , wherein the saturated solution is mixed at a temperature of about 50° C.
17. The hemostatic device of claim 14 , wherein the saturated solution is mixed for about four hours.
18. The hemostatic device of claim 14 , wherein the non-oxidized, non-regenerated Na-CMC is biocompatible, water-soluble, water-swellable, or a combination thereof.
19. The hemostatic device of claim 14 , wherein the non-oxidized cellulose is amorphous, crystalline or a combination thereof.
20. The hemostatic device of claim 14 , wherein the organic solvent is selected from the group consisting of ethanol, toluene, acetone, 2-propanol or a mixture thereof.
21. The hemostatic device of claim 20 , wherein the organic solvent is ethanol.
22. The hemostatic device of claim 14 , wherein the alkalization agent is selected from the group consisting of sodium hydroxide (NaOH), potassium hydroxide (KOH), calcium hydroxide (Ca(OH) 2 ), or a mixture thereof.
23. The hemostatic device of claim 14 , wherein alkalization solution comprises about 11% w/w NaOH solution, about 21% water, and about 68% ethanol.
24. The hemostatic device of claim 14 , wherein the monohaloacetic acid is chloroacetic acid.
25. The hemostatic device of claim 24 , wherein the monohaloacetic acid is sodium monochloroacetic acid (ClCH 2 COON a ).