Process for medical components and uses thereof

Abstract

The invention relates to a process for making a medical component such as a medical implant for example a graft or stent-graft, said medical component comprising ultra high molecular weight polyethylene (UHMWPE) fibers, a medical component obtainable by said process as well as uses of said process and medical component.

Claims

1. A process for making a medical component C, wherein the process comprises the steps of: a) providing: i) an article A comprising a fabric assembly, wherein the fabric assembly comprises ultrahigh molecular weight polyethylene (UHMWPE) fibers, and wherein the article A is hollow having an inner surface and includes at least one opening which allows access to the inner surface of article A; and ii) a shaping member B which maintains its shape when it is subjected to heating at a temperature and for a time period as described in step c); b) positioning in close proximity article A and shaping member B in such a way that at least part of the outer surface of shaping member B is surrounded by at least part of the inner surface of article A; c) heat-shrinking article A by heating at least a portion of article A that is in close proximity with a portion of shaping member B at a temperature of at least 110° C. and of most 140° C. for a time sufficient to cause said portion of article A to shrink and conform to the shape of said portion of shaping member B, thus to obtain a heat-shrunk article A having an inner surface that was contacted with the shaping member B during heat-shrinkage with Ra surface roughness as defined in ISO 4287 that is at least 10% lower as compared to an outer surface of the article A which was not contacted with the shaping member B during heat-shrinkage; and d) removing said heat-shrunk article A from shaping member B to obtain the medical component C comprising the heat-shrunk article A that is freestanding to a height of at least 4 times its diameter.

2. The process according to claim 1, wherein during the heat-shrinking of article A atmospheric pressure and/or reduced pressure is/are applied.

3. The process according to claim 1, wherein the fabric assembly consists of the UHMWPE fibers.

4. The process according to claim 1, wherein the fabric assembly comprising the UHMWPE fibers is selected from the group consisting of woven fabrics, non-woven fabrics, knitted fabrics, braided fabrics and combinations thereof.

5. The process s according to claim 4, wherein the fabric assembly is a woven fabric.

6. The process according to claim 1, wherein the positioning of article A and shaping member B is a positioning of female-to-male members, wherein article A is the female member, and shaping member Bis the male member.

7. The process according to claim 1, wherein article A is tubular.

8. The process according to claim 7, wherein article A is a tube having a longitudinal axis with at least one opening at each end thereof.

9. The process according to claim 1, wherein article A is a medical implant.

10. The process according to claim 1, wherein article A is a graft or a stent-graft.

11. The process according to claim 1, wherein medical component C is a medical implant.

12. The process according to claim 11, wherein medical component C is a graft or a stent-graft.

13. The process according to claim 1, wherein the Ra surface roughness of the inner surface is at least 25% lower than the Ra surface roughness on the outer surface of the heat-shrunk article A.

14. The process according to claim 1, wherein the Ra surface roughness of the inner surface is at least 50% lower than the Ra surface roughness on the outer surface of the heat-shrunk article A.

15. The process according to claim 1, wherein the heat-shrunk article A is freestanding to a height of at least 5 times and less than 20 times its diameter.

Description

EXAMPLES

Examples According to the Invention: Examples 1-14

(1) Fourteen grafts in the form of tubes, each of diameter slightly above 8 mm and 2 cm in length made of Dyneema Purity® 25 dTex fiber, were used as article A in Examples 1-14 (Tables 1a and 1b) to measure circumferential and longitudinal strength.

(2) Two types of grafts according to the invention were made.

Examples 1-7, Article A

(3) One type of graft was a plain weave with 8 yarns/mm, yarn directions at 90° angle (Examples 1-7, Table 1a). The number of yarns was measured on the tubes (article A). The cover factor for this type of graft was 12.6.

Examples 8-14, Article A

(4) The other type of graft was a 4-4 twill weave with 12 yarns/mm in the longitudinal axis direction and 11 yarns/mm in the circumferential direction, yarn directions at 90° angle (Examples 8-14, Table 1b). The number of yarns was measured on the grafts (article A). The cover factor for this type of grafts was 18.

Example 1-14, Shaping Member B

(5) Steel cylindrical rods, each of 8 mm in diameter and 10 cm or 50 cm in length and with a smooth surface, were used as shaping members (shaping member B in the language of the present invention) for each of the grafts of Examples 1-14.

(6) Each graft of Examples 1-14 was positioned in close proximity to the steel cylindrical rod in such a way that at least part of each steel cylindrical rod was surrounded by the total inner surface of said graft.

(7) Heat-shrinking of the grafts of Examples 1-14 has taken place for 5 min in an air-circulated oven, at temperatures as indicated in Tables 1a and 1b. Each graft was subjected to the indicated and constant temperature for 5 min and then removed from the oven and cooled at room temperature in air. The heat-shrunk grafts obtained upon removing the grafts from their metallic cylindrical rods, were the medical components C as defined herein.

(8) The rigidity of the grafts of the Examples 1-14 was assessed via tactile inspection.

(9) The smoothness of the inner surface of the grafts of the Examples 1-14 was assessed via tactile inspection and reported on a scale from 1 to 5. The rating of smoothness of the inner surface of the grafts is from 1 to 5, with 1 representing the roughest inner surface and 5 representing the smoothest inner surface. Smoothness of at least 2, preferably of at least 3 is desirable.

(10) The circumferential strength of the grafts of the Examples 1-14 was measured according to ISO 7198 section 8.3.1 on a Zwick z010 tensile meter for the non-treated grafts as well as on the heat-shrunk grafts.

(11) The circumferential strength is expressed in N/mm and is defined as:
[Maximum Load at break/twice the Length]=T.sub.max/2L (N/mm)  (1),
wherein L is the original length of the sample. The load is carried by the two sidewalls of the graft, so the line strength has to be defined using the double length

(12) The longitudinal strength of the grafts of the Examples 1-14 was measured according to ISO 7198, section 8.3.2 on a Zwick z010 tensile meter for the non-treated grafts as well as on the heat-shrunk grafts with a modification as explained herein. Due to the extremely low friction coefficient of the Dyneema® fibers and the enhanced slippage, proper clamping of the samples to the tensile meter was impossible. Therefore, the method described in ISO 7198, section 8.3.2 was modified as follows: rubber pads of 1 mm in thickness were placed between the clamps and the samples to improve grip.

(13) The longitudinal strength is also expressed in N/mm (Newton/mm) and is defined as:
Maximum Load at break/circumferential length=T.sub.max/(π.Math.D)(N/mm)  (2),
wherein D is the diameter of the graft.

Example 1-14: Permeability Testing

(14) In the case of permeability measurements fourteen grafts in the form of tubes, each of 8 mm in diameter and 40 cm in length made of Dyneema Purity® 25 dTex were used. Similarly to grafts used for circumferential and longitudinal strength tests, grafts of plain weave and grafts of 4-4 twill weave was utilized. Pieces of the grafts were placed on a steel rod of 8 mm in diameter and heat-shrunk at for 5 min at the temperatures indicated in Table 1a and 1b. Measurements to assess the permeability of the grafts were conducted on the non-treated grafts as well as on the heat-shrunk grafts as follows: The grafts (40 cm in length and 8 mm in diameter) were cleaned ultrasonically in water prior to testing. Subsequently, the grafts were closed at one end and suspended at a sidewall location such that the closed end is positioned at the lower side and the open end of the grafts was positioned at the top. After this, distilled water was being injected into the grafts from their open end with the help of syringe. The filling of the grafts with water was continued until a first water droplet was observed at the closed (lower) end of the graft. The height of the water column present in the graft at the point in time where the first water droplet was observed was recorded as a measure of permeability (10 cm water column is equivalent to a pressure of 1 kPa). The higher the height of the water column, the higher the pressure that needs to be applied in order the material to start leaking, subsequently the lower the permeability of said material is.

(15) All measurements reported herein for Examples 1-14 were carried out at room temperature.

Comparative Examples: Comp. Ex 1-4

(16) Four grafts in the form of tubes, each of 8 mm in diameter and 2 cm in length made of Dyneema Purity® 25 dTex, are used as article A in Comp. Ex 1-4 to measure circumferential and longitudinal strength.

(17) Two types of grafts are made.

Comp Ex 1-2: Article A

(18) One type of graft is a plain weave with 8 yarns/mm, yarn directions at 90° angle (Comp. Ex 1-2, Table 1a). The number of yarns is measured on the tubes (article A). The cover factor for this type of graft is 12.6. Article A of Comp. Ex 1-2 are hence similar to Article A of Examples 1-7.

Comp Ex 3-4: Article A

(19) The other type of graft is a 4-4 twill weave with 12 yarns/mm in the longitudinal axis direction and 11 yarns/mm in the circumferential direction, yarn directions at 90° angle (Comp. Ex 3-4, Table 1b). The number of yarns is measured on the grafts (article A). The cover factor for this type of grafts is 18. Article A of Comp. Ex 3-4 are hence similar to Article A of Examples 8-14

Comp Ex 1-4: Shaping Member B

(20) Steel cylindrical rods, each of 8 mm in diameter and 10 cm or 50 cm in length and with a smooth surface, are used as shaping members (shaping member B in the language of the present invention) for each of the grafts of Comp. Ex 1-4.

(21) Each graft of Comp. Ex 1-4 is positioned in close proximity to the steel cylindrical rod in such a way that at least part of each steel cylindrical rod is surrounded by the total inner surface of said graft.

(22) Heat-shrinking of the grafts of the Comp. Ex 1-4 is taken place for 5 min in an air-circulated oven, at temperatures as indicated in Tables 1a and 1b. Each graft is subjected to the indicated and constant temperature for 5 min and then removed from the oven and cooled at room temperature in air. The heat-shrunk grafts that are obtained upon removing the grafts from their metallic cylindrical rods are the medical components C as defined herein. Here it needs to be stressed out that in the case of Comp. Ex 2 and Comp. Ex 4 wherein the heat-shrinking of the grafts is taken place at 160° C., a medical component C is not obtained due to partial/full melting of article A during heating at 160° C. So, no measurements are performed on these grafts (medical component C).

(23) The rigidity and smoothness of the inner surface of the grafts of the Comp. Ex 1-4 is assessed according to the way applied in the case of Examples 1-14.

(24) The circumferential strength of the heat-shrunk grafts of the Comp. Ex 1-4 is measured according to ISO 7198 section 8.3.1 on a Zwick z010 tensile meter.

(25) The longitudinal strength of the heat-shrunk grafts of the Comp. Ex 1-4 is measured according to ISO 7198, section 8.3.2 on a Zwick z010 tensile meter with a modification as explained herein.

(26) In the case of permeability measurements four grafts in the form of tubes, each of 8 mm in diameter and 40 cm in length made of Dyneema Purity® 25 dTex are used. Similarly to grafts used for circumferential and longitudinal strength tests, grafts of plain weave and grafts of 4-4 twill weave was utilized. Pieces of the grafts were placed on a steel rod of 8 mm in diameter and heat-shrunk at for 5 min at the temperatures indicated in Table 1a and 1b. Measurements to assess the permeability of the heat-shrunk grafts of the Comp. Ex 1-4 is conducted according to the way described herein in the case of Examples 1-14.

(27) All measurements reported herein for Comp. Ex 1-4, are carried out at room temperature.

(28) TABLE-US-00001 TABLE 1a Graft (article A) Process Graft (medical component C) Permeability (only one Permeability (Pressure feature is (Pressure Smooth- [kPa] Circum- Longi- shown) [kPa] Smooth- Circum- ness applied up ferential tudinal Temperature applied up ness ferential Longitudinal Ex- Type of inner to leak strength strength (° C.) for heat- to leak of inner strength strength ample graft Rigidity surface occurs) (N/mm) (N/mm) shrinking Rigidity occurs) surface (N/mm) (N/mm) Comp. plain Supple 1 2.5 71.6 69 60 Supple 2.5 1 71.6 69 Ex 1 weave 1 plain Supple 80 Rigid 2.8 2 71.6 69 weave 2 plain Supple 90 Rigid n.m. 3 71.5 n.m. weave 3 plain Supple 100 Rigid n.m. 3 75.1 n.m. weave 4 plain Supple 110 Rigid 3   4 86.3 65 weave 5 plain Supple 120 Rigid n.m. 4 70.7 n.m. weave 6 plain Supple 130 Rigid n.m. 5 75.3 n.m. weave 7 plain Supple 140 Rigid 3.1 5 69 64 weave Comp. plain Supple 160 Medical component C is not obtained due to Ex 2 weave partial/full melting of article A during heating n.m.: Not measured

(29) TABLE-US-00002 TABLE 1b Graft (article A) Process Graft (medical component C) Permeability (only one Permeability (Pressure feature is (Pressure Smooth- [kPa] Circum- Longi- shown) [kPa] Circum- Longi- ness applied up ferential tudinal Temperature applied up Smoothness ferential tudinal Type of inner to leak strength strength (° C.) for heat- to leak of inner strength strength Example graft Rigidity surface occurs) (N/mm) (N/mm) shrinking Rigidity occurs) surface (N/mm) (N/mm) Comp. 4-4 Supple 1 2.7 67.9 37 60 Supple 2.7 1 67.9 37 Ex 3 twill w  8 4-4 Supple 80 Rigid 3   2 65.9 39 twill w  9 4-4 Supple 90 Rigid n.m. 3 66.3 n.m. twill w 10 4-4 Supple 100 Rigid n.m. 3 64.6 n.m. twill w 11 4-4 Supple 110 Rigid 3.1 3 60.6 39 twill w 12 4-4 Supple 120 Rigid n.m. 4 62.1 n.m. twill w 13 4-4 Supple 130 Rigid n.m. 4 67.6 n.m. twill w 14 4-4 Supple 140 Rigid 3.1 5 61.4 36 twill w Comp. 4-4 Supple 160 Medical component C is not obtained due to Ex 4 twill w partial/full melting of article A during heating n.m.: Not measured

(30) As it can be seen from the Examples shown in Tables 1a and 1b, medical components C (grafts in the case of the Examples) that have been prepared by a process comprising the steps of: providing: i) an article A comprising a fabric assembly said fabric assembly comprising UHMWPE fibers, said article A is hollow having at least one opening which allows access to the inner surface of article A; and ii) a shaping member B which maintains its shape when it is subjected to heating at a temperature and for a time period as described in said process; positioning in close proximity article A and shaping member B in such a way that at least part of the outer surface of shaping member B is surrounded by at least part of the inner surface of article A; and heat-shrinking article A by heating at least a portion of article A that is in close proximity with a portion of shaping member B at a temperature of at least 80° C. and of most 155° C. for a time sufficient to cause said portion of article A to shrink and conform to the shape of said portion of shaping member B, thus to obtain a heat-shrunk article A; and removing said heat-shrunk article A from shaping member B to obtain the medical component C which medical component C comprises said heat-shrunk article A,
had significantly higher rigidity, lower permeability, inner surfaces of enhanced smoothness, had substantial mechanical strength whilst at the same time the circumferential strength and longitudinal strength of the grafts were not compromised by the process.

(31) Moreover, upon visual inspection once formed the shape of each graft (medical component C) was characterized of enhanced precision in respect to the desired end shape.

Example 15: Measuring of Freestanding Height of the Grafts

(32) The freestanding Article A from Experiment 3 and Experiment 10 as well as Component C from Experiment 3 and 10 was measured according to the following method.

(33) The freestanding height of a graft is measured by inserting a cylindrical soft plastic tube in the fibrous tube. The wall thickness of the tube should be about 25% of the diameter of the tube. The outer diameter of the inserted tube should be about 90% of the diameter of the graft. The assembly of graft and inserted tube is then cut perpendicular to the longitudinal axis of the graft with a sharp hot knife having a temperature of 200° C. to 300° C. to obtain sections of the graft with a length of 4 times the diameter or more. Thereafter, the inserted plastic tube is removed. Using tweezers, the sections of the graft are thereafter placed with the longitudinal axis vertically on a horizontal flat surface with the cut edge in contact with the horizontal surface and after 10 seconds it is observed if the graft will stand or collapse.

(34) For the present experiment, a tube of 7.5 mm and wall thickness of 1.8 mm was used. The hot knife had a temperature of ca. 250° C. with a cutting speed of about 2 seconds per cut. Each graft was cut into sections of 4, 5, and 6 times the diameter of the graft. Thereafter it was established if the graft sections were freestanding.

(35) TABLE-US-00003 TABLE 2 Section height Sample 4 × diameter 5 × diameter 6 × diameter Component C Experiment 3 Freestanding Freestanding Freestanding (heat-shrunk) Component C Experiment 10 Freestanding Freestanding Freestanding (heat-shrunk) Article A Experiment 3 Not Not Not (not heat-shrunk) freestanding freestanding freestanding Article A Experiment 3 Not Not Not (not heat-shrunk) freestanding freestanding freestanding
Experimental results are presented in Table 2. It was found that grafts not being subjected to the process of the invention typically will top over at a length of less than 4 times the diameter of the graft. Grafts according to the invention however typically are freestanding for length of at least 4 times the diameter of the graft and may be freestanding even up to lengths of 10 times the diameter if the process is performed under the most preferred conditions.

(36) The large freestanding height of the grafts according to the invention allow shipping when packed in long rigid tubes without flattening, thus allowing arrival to the location where they are combined with a stent or (if no stent is connected to the graft) directly to the surgery room, still exhibiting the shape of the shaping member B and free of folds or wrinkles.