Resorbable laparoscopically deployable hemostat

Abstract

The present invention is directed to a resorbable hemostatic nonwoven felt suitable for use in laparoscopic procedures and to methods for manufacturing said felt.

Claims

1. A method of manufacturing a resorbable hemostatic dressing comprising a single layer of three-dimensionally entangled nonwoven felt that is not separable into distinct layers by hand consisting essentially of oxidized cellulose fibers, wherein the felt has sufficient mechanical strength and flexibility to retain its structural integrity when deployed laparoscopically, said method comprising the steps of: a) providing cellulose yarn having filaments of minimal twist; b) forming a multi-yarn, single feed circular knitted cellulose fabric having minimal twist; c) scouring the cellulose fabric; d) oxidizing the scoured fabric; e) pliabilizing the oxidized fabric; f) de-knitting the pliabilized fabric to form a continuous strand having a crimp from about 5 crimps/inch to about 12 crimps/inch; g) cutting the continuous strand to form staples, said staples having length from about 1 to about 4 inches; h) carding the staples into a carded batt; and i) needle-punching and three-dimensionally entangling the carded batt to form a single layer non-woven felt.

2. The method according to claim 1, wherein the steps of de-knitting and cutting are performed at low tension or minimal time at high tension.

3. The method according to claim 1, wherein the step of de-knitting is performed without subsequent spooling and followed immediately by cutting.

4. The method according to claim 1, wherein the carded batt comprises approximately 10 to 17 layers of carded web.

5. The method according to claim 4, wherein the carded batt comprises about 12 layers of carded web.

Description

DESCRIPTION OF DRAWING

(1) Referring now to FIG. 1, trocar insertion force (dry) for a rectangular sample of the resorbable hemostatic nonwoven felt of the present invention having dimensions of 1 inch2 inches is shown as a function of the basis weight, as measured by an Instron machine for insertion into a 5 mm diameter trocar, for the felt of the present invention, indicating acceptable insertion forces. It was discovered that the felt retained structural integrity after the insertion, as indicated by absence of tear and approximately same geometric area after deployment.

(2) The insertion force was measured by mounting a laparoscopic dissector in a jig to the top moving-head of an Instron material test machine 5544 with a 100 lb load cell. A 5 mm Ethicon Endosurgery Endopath Xcel trocar was then mounted in the non-moving base. The 1 in2 in rectangular test article was grasped at a corner in the dissector and inserted through the trocar at 0.5 inch/sec. by the Instron. The compression stress time-course was measured and recorded by the Instron software.

(3) According to an embodiment of the present invention, the resorbable hemostatic nonwoven felt was further characterized by the insertion force for deploying the rectangular sample having dimensions of 1 inch2 inches through the laparoscopic trocar:

(4) less than 89 newtons [20 LBF] for the felt having the basis weight of from about 150 to about 200 grams per meter squared;

(5) less than 35.6 newtons [8 LBF] for the felt having the basis weight of from about 100 to about 125 grams per meter squared; or

(6) less than 13.3 newtons [3 LBF] for the felt having the basis weight of from about 70 to about 80 grams per meter squared.

(7) Upon exiting from trocar, the felt of this invention was observed to be easier to manipulate and position and the felt was less wrinkled when compared to known knitted hemostats. The felt was exiting from trocar quickly and without additional unfurling effort reverted to the pre-insertion shape, exhibiting resilient compressibility and having sufficient mechanical flexibility, strength, and basis weight for effective use as a hemostat for effective laparoscopic deployment. In comparison marketed non-woven fibrillated non-entangled ORC material with basis weight of from 200 to 400 grams/meter squared was not possible to insert into trocar. When a few layers peeled from the marketed non-woven fibrillated non-entangled ORC material with basis weight of from 200 to 400 grams/meter squared were inserted into the trocar, the inventors found that such modified sample has lost structural integrity during trocar deployment and exhibited tears and damage.

(8) According to an embodiment of the present invention, the resorbable hemostatic nonwoven felt is made of yarn which is 150 Denier 42-filament yarn, 100 Denier 90-filament yarn, 60 Denier 24-filament yarn, or combinations thereof.

(9) According to an embodiment of the present invention, the resorbable hemostatic nonwoven felt is made of yarns characterized by crimp from about 5/inch to about 12/inch and comprises staples having length from about 1 to about 4 inches.

(10) The inventors have unexpectedly discovered a method of manufacturing and a resulting material which has desirable hemostatic and mechanical properties and is deployable laparoscopically. Specifically, the material has hemostatic properties similar to non-woven oxidized regenerated cellulose materials and mechanical properties enabling laparoscopic deployment similar to knit or woven oxidized regenerated cellulose materials

(11) According to an embodiment of the present invention, the resorbable hemostatic nonwoven felt is manufactured by a method comprising the steps of

(12) providing regenerated cellulose yarn having filaments of minimal twist;

(13) forming a multi-yarn, single feed circular knitted cellulose fabric having minimal twist of the yarns;

(14) scouring the cellulose fabric;

(15) oxidizing the fabric;

(16) pliabilizing the fabric;

(17) de-knitting the fabric forming a continuous strand having a crimp from about 5 crimps/inch to about 12 crimps/inch;

(18) cutting the continuous strand to form staples, said staples having length from about 1 to about 4 inches;

(19) carding the staple yarn into a carded batt;

(20) needle-punching and three-dimensionally entangling the carded batt and forming a single layer non-woven felt;

(21) wherein

(22) the steps of de-knitting and cutting are performed at low tension or minimal time at high tension, preserving the crimp;

(23) the step of de-knitting is performed without subsequent spooling but with immediately following step of cutting resulting in preserving crimp;

(24) the carded batt comprises approximately 10 to 17 layers of carded web, preferably about 12 layers of carded web.

(25) The resorbable hemostatic nonwoven felt was further found to have improved properties of being less adherent to the surgical tools and other materials within the surgical operational space, especially when exposed to contact with wet materials and surfaces, and simultaneously provides hemostasis similar to or better than conventional and known cellulose-containing hemostatic wound dressings. Comparative evaluations of the degree to which ORC-based hemostatic agents adhered to surgical instruments and gloves were conducted on the present resorbable hemostatic nonwoven felt in comparison to known marketed non-woven fibrillated non-entangled ORC material. The evaluations were conducted by 21 surgeons (divided between general and trauma surgeons from United States and Europe) with >95% of surgeons finding the inventive resorbable hemostatic nonwoven felt less adhering than known marketed non-woven fibrillated non-entangled ORC material.

(26) In one preferred embodiment, for a 150 denier/42 filament yarn, the diameter of an individual fiber was approximately 18 to 25 microns as measured from SEM image, so the fibers and the yarns used had 150/42 denier per filament (dpf) (3.6 dpf) down to 100/90 (1.1 dpf) or approx 5 microns diameter to 25 microns diameter for the filaments.

(27) In the preferred embodiment, the felt is formed of fibers having uniform staple length and or controlled staple length distribution, and lesser amount of fines which are defined as short easily shed fibers fragments. Known ORC-based non-woven materials have higher amount of fines. In comparison marketed non-woven fibrillated non-entangled ORC material with basis weight of from 200 to 400 grams/meter squared had wider distribution and much shorter staples about 0.5-0.6 inch long.

(28) In the preferred embodiment, the felt is a single layer felt and has no layers peelable from each other. In comparison marketed non-woven fibrillated non-entangled ORC material with basis weight of from 200 to 400 grams/meter squared has a plurality of layers that are separable in layers and has a much lower Z-strength. Material was delaminating when attempted to be mounted in the test jig for peeling test.

(29) In the preferred embodiment, the felt has higher entanglement and interlocking of the fibers compared to the known non-woven oxidized regenerated cellulose based hemostatic materials. Mechanical Z-direction entanglement process of needlepunching is utilized. Other types of 3D entanglement can be utilized for instance hydro-entanglement. In comparison marketed non-woven fibrillated non-entangled ORC material with basis weight of from 200 to 400 grams/meter squared has manufacturing method lacking needlepunching process step providing for 3D entanglement.

Example 2. Wet Insertion Through Trocar

(30) For a wet insertion through trocar for a rectangular sample having dimensions of 1 inch2 inches, it was discovered that the felt retained its structural integrity after the insertion. According to an embodiment of the present invention, the resorbable hemostatic nonwoven felt further has improved properties of being less adherent to the surgical tools and other materials within the surgical operational space, especially when exposed to contact with wet materials and surfaces, and simultaneously provides hemostasis similar to or better than conventional and known cellulose-containing hemostatic wound dressings. Comparative laparoscopic handling evaluations were conducted on the inventive resorbable hemostatic nonwoven felt against marketed fibrillated ORC by 21 surgeons (divided between general and trauma surgeons from United States and Europe) with majority (>80%) favoring laparoscopic handling characteristics of the inventive resorbable hemostatic nonwoven felt.

Example 3. Hemostatic Activity

(31) The Hemostatic activity of the resorbable hemostatic nonwoven felt of the present invention was tested using The Acute Swine Splenic Incision Hemostasis Model. In the Linear Incision Spleen Model 15-mm long3-mm deep incisions were made on the spleen and the test or control article (A, B, C, or E) was applied to a freshly created wound site followed by an occlusive digital pressure (tamponade). Pressure was initially applied for one minute and was timed using an electronic timer. Following the one-minute initial tamponade, digital pressure was discontinued; the gauze pad on the article was immediately removed. A 30-second hemostasis evaluation period was performed. If free flow bleeding was not observed within 30 seconds, the time to hemostasis was noted, in a minutes: seconds format, and testing was concluded for that article. If free flow bleeding was observed, pressure and gauze were reapplied for additional 30 second tamponade and observation periods until hemostasis was achieved or until the testing period reached ten minutes. At ten minutes, the trial was aborted as a complete failure and recorded as >10:00 (greater than ten minutes) in the raw data. Hemostasis was determined by the cessation of free flow bleeding in less than ten minutes.

(32) The results of the testing of hemostatic activity are shown in Tables 1-3. Tables 1 and 2 represent two different sets of experiments. Table 3 represents a summary of the result of Table 2. Test articles for Tables 2 and 3: Control used was gauze which represented negative control. AMarketed woven hemostat, single layer BDouble layer of the article A CSingle layer of resorbable hemostatic nonwoven felt of the present invention, made from 150 denier circular fiber yarn, oxidized, and made into a non-woven of 100-110 gsm basis weight, packaged in foil and gamma sterilized to a minimum of 30 kGy EDouble layer of the article C
Approximately 1.5 cm2.5 cm rectangular pieces of the test articles were used

(33) Fast time to hemostasis for the resorbable hemostatic nonwoven felt of the present invention was observed in all tests. Advantageously, time to hemostasis was independent of the number of layers of the resorbable hemostatic nonwoven felt.

(34) TABLE-US-00001 TABLE 1 Number of Layers of resorbable Hemostasis Hemostasis Hemostasis Hemostasis hemostatic Time, min Time, min Time, min Time, min nonwoven felt Animal 1 Animal 2 Animal 3 Animal 4 1 5:45 5:15 6:16 6:02 2 5:31 5:47 7:33 4:14 3 5:50 6:53 6:25 4:16

(35) TABLE-US-00002 TABLE 2 Time to hemostasis, min Test test test test test test test test test test test test test article 1 2 3 4 5 6 7 8 9 10 11 12 Control >10 >10 >10 >10 >10 >10 >10 >10 >10 >10 >10 >10 A >10 8:25 >10 >10 5:28 >10 9:00 8:22 >10 >10 >10 >10 B 8:18 8:20 9:32 8:36 7:05 6:56 6:09 5:56 9:02 8:45 8:19 7:59 C 5:35 4:32 5:44 5:22 9:30 5:42 9:58 5:43 8:02 7:46 5:04 6:00 E 7:25 4:40 4:13 5:04 3:43 6:02 5:52 3:46 6:44 4:36 4:08 6:22

(36) TABLE-US-00003 TABLE 3 Test article Average Time to hemostasis, min Control >10 A >10 B 8:18 C 5:43 E 4:52

Example 4. Tear Strength

(37) Tear strength in machine direction cut of the resorbable hemostatic nonwoven felt of the present invention was measured. The tear strength was tested using Instron material testing machine and demonstrated high strength for a non-woven ORC material.

(38) Instron material testing machine was 5500R: TJ 8, having 10 lbs load cell and 90 PSI grips with 11.5 inch smooth steel faces. The samples cut in machine direction were provided for tear strength test. Sample preparation included cutting 1 inch in length tear using scissors. This was done to allow clamping of the samples into the Instron grips and to initiate a tear in a controlled direction. The distance between the Instron grips (gauge length) was set at 1 inch. The either side of the cut edge of the sample was loaded on the Instron grips such that 0.5 inch of sample length is inside the grips. The Instron cross head moved at 12 inch/min to propagate the tear along the sample. The test was manually stopped when the tear propagated through the sample. The results of the measurements are presented in Table 4.

(39) TABLE-US-00004 TABLE 4 Machine direction tear strength Cross machine direction Strength Strength (lbs) Extension (in) (lbs) Extension (in) LOT A SAMPLE 1 0.206 6.8 0.279 2.910 LOT A SAMPLE 2 0.244 5.33 0.116 2.640 LOT A SAMPLE 3 0.212 8.48 0.198 2.430 Average LOT A 0.221 6.87 0.198 2.660 LOT B SAMPLE 1 0.188 2.330 0.206 2.510 LOT B SAMPLE 2 0.224 6.010 0.218 2.760 LOT B SAMPLE 3 0.216 6.750 0.192 2.450 Average LOT B 0.209 5.030 0.205 2.573 LOT C SAMPLE 1 0.198 6.920 0.213 6.710 LOT C SAMPLE 2 0.232 6.740 0.098 1.220 Average LOT C 0.215 6.83 0.143 3.926 AVERAGE OF 0.215 6.17 0.19 2.95 ALL SAMPLES

Example 5. Tensile Strength and Water Absorbability

(40) Tensile strength was measured in a similar test as described in the Example 4 using an Instron machine and testing the tensile strength in longitudinal direction. All samples tested were 12 inch rectangular samples. The results of testing are presented in Table 5.

(41) The water absorbability was tested according to the following procedure. The test includes weighing the sample, saturating the sample with water, letting the excess water to drain for a specified time, weighing the sample with water. The results of testing are presented in Table 5.

(42) The water absorbability for different lots of material from over 850% to over 1000% of weight of water retained as a function of the weight of the resorbable hemostatic nonwoven felt. Comparison with marketed woven and knit ORC based hemostats in the same test indicated lower water absorbability: 360% (basis weight 188.1); 333% (basis weight 253); 136% (basis weight 431).

(43) TABLE-US-00005 TABLE 5 LOT NUMBER 150/42 H 60/24 H 100/90 H Average Tensile Strength, lbf, 5.28 2.62 3.42 Machine Direction Average Tensile Strength, lbf, 2.53 1.96 1.16 Cross Machine Direction TEST NUMBER 1 2 3 1 2 3 1 2 3 Basis weight, g/m.sup.2 125.9 93.2 116.1 126.4 116.1 102.7 108.5 110.7 87.3 % Water absorption 1049.9 1065.1 976.7 893.2 858.5 854.4 950.0 896.1 949.4