Chitosan fiber

Abstract

A fluid-swellable fiber in particular for the use as a surgical suture, the fiber comprising chitosan, the fiber's swelling ratio being less than 100%, and a fabric comprising the fiber. Moreover, a method of manufacturing from a chitosan-containing solution a fiber comprising chitosan, wherein during manufacture, the solution is brought into contact with a coagulation medium containing at least one organic solvent, a method of removing a fiber from a living organism, wherein the fiber is at least partly dissolved in a solvent applied from the outside, and a kit comprising a chitosan containing fiber and a solvent for at least partly dissolving the fiber.

Claims

1. A fluid-swellable fiber comprising more than 90% by weight of chitosan, wherein: the diameter of the fiber is at least 0.05 millimeters, the fiber's swelling ratio is 80% or less, and the swelling ratio defines a change in mass calculated according to formula:
(m.sub.w−m.sub.d)/m.sub.d×100%,  wherein: m.sub.d is the mass of the dry fiber before contact with an aqueous solution, and m.sub.w is the mass of the fiber after saturation with a physiological solution.

2. The fiber of claim 1, wherein the fiber's swelling ratio is between 60% and 70%.

3. The fiber of claim 1, wherein the fiber's swelling ratio is more than 10%.

4. The fiber of claim 1, comprising a chitosan component that is dissolvable in an aqueous medium, the solubility of the chitosan component depending on the pH.

5. The fiber of claim 1, comprising a chitosan component that has a degree of acetylation of more than 60% or less than 40%.

6. The fiber of claim 1, comprising non-cross-linked chitosan.

7. The fiber of claim 1, comprising a native chitosan.

8. The fiber of claim 1, comprising a combination of chitosan and at least one other polymer.

9. A process for carrying out surgical suturing comprising: using a fluid-swellable fiber comprising chitosan as a surgical suture, wherein: the fiber comprises more than 90% by weight of chitosan, the diameter of the fiber is at least 0.05 millimeters, the fiber's swelling ratio is 80% or less, and the swelling ratio defines a change in mass calculated according to formula:
(m.sub.w−m.sub.d)/m.sub.d×100%,  wherein: m.sub.d is the mass of the dry fiber before contact with an aqueous solution, and m.sub.w is the mass of the fiber after saturation with a physiological solution.

10. A fabric comprising at least one fiber of claim 1.

11. A method for manufacturing, from a chitosan-comprising solution, a fluid-swellable fiber comprising chitosan, wherein: the fluid-swellable fiber comprises more than 90% by weight of chitosan, the diameter of the fluid-swellable fiber is at least 0.05 mm, the swelling ratio of the fluid-swellable fiber is 80% or less, the swelling ratio defines a change in mass calculated according to formula:
(m.sub.w−m.sub.d)/m.sub.d×100%,  wherein: m.sub.d is the mass of the dry fiber before contact with an aqueous solution, and m.sub.w is the mass of the fiber after saturation with a physiological solution, the method comprising: bringing the chitosan-comprising solution into contact with a coagulation medium, wherein the coagulation medium comprises at least one organic solvent.

12. The method of claim 11, wherein the coagulation medium comprises at least 50% of the at least one organic solvent.

13. The method of claim 11, comprising the step of acylating the chitosan in the fluid-swellable fiber.

Description

BRIEF DESCRIPTION OF THE DRAWING

(1) The invention is illustrated in greater detail with the aid of a schematic drawing.

(2) FIG. 1 shows a fiber according to the invention formed into a simple knot. Not drawn to scale.

(3) FIG. 2 shows a suture material according to the invention. Nat drawn to scale.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS OF THE INVENTION

Example 1

Fabrication of Chitosan Monofilament

(4) 50 ml of a solution of 4% chitosan in 2% acetic acid were mixed with an equal amount of N-methylpyrrolidone (NMP) and filled in a 0.1 liter (L) glass container equipped with a cap containing 2 outlets. One outlet is connected to an air compressor, and the other outlet connects the chitosan solution to a needle of 50 mm in length and an inner diameter of 1.0 mm. The needle is dipped into a coagulation bath containing a mixture of 2 L of NMP and 3 milliliters of 25% aqueous ammonia solution. The air pressure is adjusted to 490 millibar±20 millibar, to extrude the chitosan solution into the coagulation bath.

(5) After completion of the extrusion, the fiber is left in the coagulation bath over night. It is then washed in a mixture of distilled water containing 0.1% by weight of a 25% aqueous ammonia solution for 2 hours. For a second washing step, the solution is replaced by a mixture of distilled water containing 0.1% by weight of a 25% by weight aqueous ammonia solution and 1% by weight of glycerol as plasticizer to wash the fiber for another 2 hours. In some experiments, 0.01% by weight of indigocarmine was added to this mixture for blue staining. After the washing steps, the fiber is removed from the bath, and dried at room temperature while being wound up at a speed of 1 meters/min.

(6) Monofilaments 1 (schematically shown in FIG. 1) of several hundred meters length were obtained by this method. Moreover, short-length monofilaments (as sufficient for sutures) were obtained by winding up the monofilament 1 directly on metallic holders being 50 centimeters (cm) apart from each other for drying at room temperature over night. The chitosan monofilament 1 resulting this way had a diameter of approximately 0.17 mm.

(7) Chitosan monofilaments 1 of different diameters were produced by using needles of different inner diameters.

Example 2

Acetylation of Chitosan Monofilament

(8) 29.3 g of chitosan monofilaments 1 manufactured as described in Example 1, except of the drying step, were treated with 1 L of a 0.01% by weight solution of acetic anhydride in a mixture of NMP/water at a ratio of 60/40 by volume for 2 hours under gentle shaking, and then washed and dried as described in Example 1, resulting in an N-acetylchitosan monofilament.

(9) Fabrication of Chitosan Suture

(10) Monofilaments 1 fabricated as described in Examples 1 and 2 (dried on holders) were cut to a length of 45 cm, and needles 2 of the type DS 19 (for 0.17 mm monofilaments 1) and DS 30 (for 0.34 mm monofilaments 1) were attached, using standardized procedures, by Feuerstein GmbH (Berlin, Germany). An example of a chitosan suture is shown in FIG. 2.

(11) Swellability

(12) Chitosan monofilaments 1 and sutures produced as described in Examples 1 to 3, were weighted, and then placed in a 0.9% aqueous NaCl solution of pH 7.0 for 1 hour. The mass of the wet monofilament 1 was compared to the mass of the dry monofilament 1, and the swelling ratio calculated. Examples are given in Table 1.

(13) TABLE-US-00001 TABLE 1 No. Sample Diameter (mm) Swelling ratio (%) 1 chitosan 0.05 42 2 chitosan 0.08 47 3 chitosan 0.17 65 4 chitosan 0.34 63 5 chitosan 0.44 76 6 N-acetylchitosan 0.34 97

(14) Mechanical Properties

(15) Mechanical strength of chitosan and N-acetylchitosan monofilaments 1 and sutures produced as described in Examples 1 to 3 were tested according to the procedure specified in the European Pharmacopoeia 4, ref. 01/2002:0666. Knots 2 as shown in FIG. 1 where formed and knot strengths were measured. Examples for knot strengths are given in Table 2.

(16) TABLE-US-00002 TABLE 2 Breaking load No. Sample Diameter (mm) (N) 3 chitosan 0.17 5.7 4 chitosan 0.34 16.9 6 N-acetylchitosan 0.34 7.0

(17) Needle Attachment

(18) Needle 2 attachment of chitosan and N-acetylchitosan sutures produced as described in Examples 1 and 2 were tested according to the procedure specified in the European Pharmacopoeia 4, ref. 01/2002:0666. Examples for needle 2 attachment strengths are given in Table 3.

(19) TABLE-US-00003 TABLE 3 Breaking load No. Sample Diameter (mm) (N) 3 chitosan 0.17 6.5 4 chitosan 0.34 11.1 6 N-acetylchitosan 0.34 13.3

(20) Biocompatibility

(21) Chitosan suture (0.24 mm diameter) was fabricated as described in Example 3 and sterilized using an electron beam. 10 NMRI mice were anesthetized, and a 1.5 cm long piece of the suture implanted subcutaneously in the neck of each animal. The neck incision was closed by a conventional, non-absorbable suture. No infection or immunogenic reaction was observed in the macroscopic follow-up. After 4, 8, and 12 weeks, the chitosan samples were explanted, and the area of implantation was analyzed histologically. None of the tissue samples showed signs of inflammation or other changes. After 4 weeks, blood samples were taken and controlled for chronic inflammation, by analysis of the number of leukocytes. It was found that in all animals the number of leukocytes was in the normal range indicating no inflammatory reaction to the chitosan material.

(22) Biodegradation

(23) Samples of chitosan suture, obtained from the implantation study described in Example 7, were tested for tensile strength 4, 8, and 12 weeks post-implantation. Breaking loads were found to decrease to 41, 26, and 11%, respectively.

(24) Controlled Dissolution

(25) Chitosan suture of 0.24 mm in diameter was fabricated as described in Example 3 and sterilized using electron beam. 6 NMRI mice were anesthetized, and the suture, using 3 stitches each, applied to the neck of each animal. One week post-implantation, a gelatin gel, adjusted to pH 5 using diluted acetic acid, was applied externally to the implant area of three of the animals. Essentially complete dissolution of the accessible suture material was observed within 4 hours of gel application. The remaining three animals were treated the same way 4 weeks post-implantation, leading to similar results.

(26) The features described in the above description, claims and figures can be relevant to the invention in any combination. The reference numerals in the claims have merely been introduced to facilitate reading of the claims and are by no means meant to be limiting.