JPH0370499B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to surgical instruments made from polymers of p-dioxanone, and more particularly to surgical instruments formed from such polymers having improved in-vivo performance characteristics. It is well known that many and various surgical procedures very often involve the implantation of synthetic devices, ie, devices made of foreign materials. An example of such a procedure is surgery that uses tantalum or stainless steel or other metal clips to control bleeding by ligating various blood vessels or other tubular organs during the surgical procedure. Additionally, in other surgical procedures, various other metal rods, staples, clips or sheets of material are implanted for various supports during the surgical procedure or for other reasons. Although in most cases these devices remain in the patient's body for a significant period of time, in some cases they must be removed at some later time or the natural physiology of the human body They may even be rejected. In many cases, these metal instruments, while not causing any harm from a medical standpoint, seriously interfere with the patient's post-operative X-ray procedure and subsequent diagnostic imaging of the patient. , it is desirable not to allow it to remain in the human body. Metallic materials not only interfere with X-ray imaging, but also modern computer-controlled axial tomography and other new diagnostic imaging procedures. Therefore, it is desirable to replace surgical instruments with non-metallic, biocompatible materials that do not have an interfering effect on new diagnostic imaging procedures. In many cases, treatments are made of absorbable polymers that are absorbed by the human body after they have performed their desired function and thus do not affect subsequent diagnostic imaging, etc. It is further desirable to manufacture devices. Absorbable polymer devices also prevent long-term problems that can result from retaining foreign material in the tissue. Surgical instruments and desirable absorbable polymers are disclosed in more detail in US Pat. No. 4,052,988, issued October 11, 1977, which is incorporated herein by reference.
Specific methods for the manufacture of such surgical instruments made of these absorbable polymers are described in co-pending patent application filed on the same date as this specification.
Disclosed in the issue. In this patent application,
A method for manufacturing molded surgical instruments from polymers of p-dioxanone is described. Although surgical instruments made according to the methods described in the above patent applications have strength and other properties desirable for many surgical procedures, the strength and other properties of surgical instruments made from these polymers are limited. Further improvements in functional integrity, flexibility, and especially tactility and audibility are still important. These improved properties expand the potential applications for the instrument and improve the reliability, stability, and in-vivo behavior of such surgical instruments. What we have discovered is a method for thermally molded surgical instruments made from polymers of p-dioxanone that increases the strength and functional integrity of the instrument while also improving its audibility and tactility. Tempering is a heat treatment method. The audibility and tactility of instruments can be further explained by understanding that in many surgical procedures, surgeons work with a limited field of view. The advantages that the clip according to the invention has compared to conventional clips when working in this way are:
This means that surgeons can rely on touch and hearing to know when a particular step in a surgical procedure is complete. For example, when closing a blood vessel with a latch clip, the surgeon cannot see this step and therefore there is no resistance (tactile) to closing the clip and a click or snap when closing the latch. I have no choice but to rely on the sound (audibility). The inventors have found that the novel method of the present invention surprisingly improves these properties in surgical instruments made of polymers of p-dioxanone. The novel method of the present invention also provides surgical instruments with improved shelf life in that the instruments are better resistant to hydrolysis caused by residual moisture in the packaging. In accordance with the present invention, a novel method for treating injection molded surgical instruments made of polymers of p-dioxanone to improve both of the aforementioned properties consists of: The device is dried under a nitrogen atmosphere at a temperature not exceeding 30° C. for a period sufficient to substantially remove all moisture from the device. Dry the utensils in an oxygen-free, inert dry atmosphere, preferably a nitrogen atmosphere, at a temperature of 50-90 °C, preferably 80-80 °C without constraining the dry equipment.
Heat at a temperature of 85°C for at least 7 hours. The novel product of the invention thus obtained is an injection molded surgical instrument consisting of a polymer of p-dioxanone having a density of at least 1.384 g/cm ³ and a crystallinity of at least 43%, preferably at least 45%. . The novel surgical instrument of the present invention has the general formula produced by a polymer consisting of units having
In the above formula, x is the degree of polymerization in the desired polymer. This polymer has the following formula Manufactured from monomers with The surgical instrument of the present invention is manufactured by an injection molding process. A specific and preferred method of injection molding is described in co-filed patent application Ser. By drying the molded polymer, substantially all of the moisture in the molded product is removed. The polymer is dried at a temperature below 30° C. with a nitrogen purge to remove substantially all moisture and reduce the potential for hydrolysis of the absorbent polymer. After drying the molded product, it is
The atmosphere is an inert, oxygen-free gas, preferably nitrogen for economy, although inert gases other than nitrogen may be used. The molded article in a dry, inert atmosphere is heated at a temperature of 50°C to 90°C, preferably 80 to 85°C, for at least 7 hours. During this heating operation, the equipment is placed under unrestrained conditions. Here, "placing the instrument under unrestrained conditions" means that the surgical instrument is not held by restraint means when the surgical instrument is heat treated. This restraining means is often referred to as an "annealing rack." The purpose of conventional annealing racks is to prevent deformation of the device during heat treatment. Unlike this conventional heat treatment process,
In the present invention, restraints such as annealing racks are not used and the surgical instrument is heat treated without restraint. In the present invention, the surgical instrument is heat treated, for example by simply placing it in an oven and heating it to the desired temperature. The molded product is then packaged,
Sterilize, dry and prepare for use. Generally, the polymers used in accordance with the present invention are sterilized by treatment with ethylene oxide, as is known in the art. The above treatments improve the strength of various forms used in surgical instruments. This method not only improves the baseline or initial strength of the device, but also reduces the amount of strength that the device loses while in vivo. The tempering process according to the present invention further improves both the tactile and audible response of surgical instruments manufactured by the method of the present invention and greatly improves the shelf life of the instruments by increasing their hydrolytic resistance. do. The tempering process of the present invention is believed to produce crystallites within the molded article that enhance its hydrolysis resistance and improve the strength and functional integrity of the molded article. The novel surgical instruments of the present invention made from polymers and copolymers of p-dioxanone comprise at least
It has a density of 1.3845g/ ^cm3 . It is essential that the device has this density in order to have the improved properties mentioned above. Furthermore, the novel surgical instruments of the present invention have a crystallinity of at least 43%, preferably 45%. Clip crystallinity is a measure of clip strength and functional integrity. X-ray diffraction is a convenient method for determining the amount and type of crystallization in clips. X-ray crystallinity data are obtained using a Phillips vertical goniometer equipped with a graphite crystal monochromator and a scintillation detector connected to a strip chart recorder.
Using CuKa radiation and mounting the sample, measurements are made using parafocusing geometry. The diffractogram obtained for the sample is analyzed for crystallinity and amorphous content using a DuPont curve analyzer. Reference is now made to the drawings, which illustrate some specific types of surgical instruments of the present invention that can be manufactured by the method of the present invention. FIG. 1 shows a ligating clip 10. This clip is used to ligate blood vessels during various surgical procedures.
The clip consists of two leg members 11 and 12 joined at their proximal ends by a hinged portion 13. This leg member has both ends 14 and 15
to secure it. FIG. 2 shows the clip of FIG. 1 in its closed position, occluding the lumen of blood vessel 16. When using this clip, the surgeon very often has to position it where the eye cannot see, so it is important to feel the resistance of the hinge and latching mechanism: That is, surgical instruments require tactile feedback. The surgeon also desires to hear an audible click as he deflects the leg member 11 and grabs the opposite leg member 12. Another thermally shaped surgical instrument is shown in FIG. This device is a two-part fastener for closing wounds and the like. The fastener consists of a staple 21 and a receiver 22 for the staple. FIG. 4 shows yet another thermally formed device 25 for use in closing wounds, whether in the skin, fascia, or muscles. The device consists of a thin elongated section 26 and crossbars 27 located at its ends. Using a suitable tool with a hollow needle to hold the device, insert the needle into the tissue, as shown in FIG.
A long section 26 that spans the wound area using this instrument.
The wound is closed by crossbars 27 which grip both sides of the wound area. Other surgical instruments within the scope of the invention include solid articles such as orthopedic pins, clamps, screws and plates; clips, clasps, hooks, buttons and clamps; jaw prostheses and the like. needles; intrauterine instruments; various tubes such as ureters, cystic ducts, etc.; surgical instruments, vascular tubes, connectors or supports; and vertebral pelvises, and other similar It is a device of. The in-vivo strength properties of the surgical instrument according to the invention are of critical importance. It is imperative that a surgical instrument retain its desired functionality over an extended period of time when placed in a slowly absorbing environment, such as biological tissue. The instrument must remain strong for a sufficient period of time to perform the desired job in such an environment. The novel device according to the invention has excellent in-vivo properties, as further illustrated in the specific examples below. EXAMPLE A large number of clips are injection molded as described in co-pending patent application no. These clips have the configuration shown in FIG. 1 and are processed in accordance with the present invention. The clips are washed twice for 15 minutes in an isopropanol bath with agitation.
Approximately 1 ml of isopropanol is used per clip in the washing step. Pour off the alcohol and place one layer of paper clips in a flat dish.
Dry under reduced pressure for 16 hours to remove alcohol. 20
Remove individual cleaned clips, measure their density and test for opening and hinge forces. Density is measured using a density gradient column prepared according to the method of ASTM D-1505. (The density gradient used spans densities from 1350 to 1400, encompassing the typical range observed for polydioxanone clips). A standard calibrated density float is placed in a column graduated in millimeters and allowed to settle to various positions in the gradient column.
Record the density and location of each standard density float. Plot the relationship between density and position in the column to obtain a linear relationship. Place the three clips into the gradient density column and allow to settle for 5-10 minutes. Record the position of the clip. Find the average clip position. The corresponding clip density can be determined by the linear relationship between density and column position. Clip hinge strength is the force required to break the clip in the hinge area and is measured as follows: Cut off the latching mechanism at the tip of the clip and place the cut end of the leg member into the opposing grips of the Instron tensile tester.
The grip has a steel surface. Move the grip using an extension rate of 5 mm/min and measure the force in Kg required to break the hinge. The opening force of a clip is the force required to open the clip after it has been closed, and is measured as follows. Close the clip over two pieces of mylar polyester film in a row. The film piece is 4 mm wide, 178 mm long, and 0.076 mm thick. Separate the ends of the film strip and bend into opposing U shapes. One end of the U-shaped piece is placed in the grip of the Instron tensile tester, while the opposite end of the U-shaped piece is placed in the opposite grip of the Instron tensile tester. The grip has a steel surface. Move the grip using an extension rate of 5 mm/min and measure the force in Kg required to open the clip. The crystallinity of the clip is determined as described above. Place the remaining clips in a heater and heat treat. Nitrogen is passed over the clip at a rate of 250 cubic feet per minute at room temperature. The temperature in the heater is then raised to 85°C and maintained at that temperature under a nitrogen flow of 50 cubic feet per minute. After 8 and 16 hours, the clips are removed, placed in a desiccator, and cooled under vacuum. Place 10 paper clips in each bag in foil bags. The bag is sterilized with ethylene oxide, degassed and sealed in a nitrogen atmosphere. The clips are measured for density and crystallinity and tested for opening strength and hinge strength. The results of the test are shown in Table 1 below.

[Table] Audible/tactile response None Significant Significant
As can be seen from the table above, the clips treated according to the invention have a greater degree of crystallinity, are denser and have improved strength than the untreated clips. Untempered, 8 hour tempered, and 16 hour tempered clips are tested for in vivo strength retention. In-vivo strength properties are measured as follows.
Open the package containing the clips from each lot and remove the clips. Divide these clips into groups of 10 each without any obvious bias. Each group corresponds to one interval of the hinge strength test. Specialized Long-Evans rats weighing 150-300 g are allowed to acclimate for at least 1 week before surgery. After each mouse is prepared for surgery and anesthetized, two clips are implanted into each mouse. The clips are implanted into the dorsal skin of the right and left buttocks of the rat. Five mice are euthanized at various times after implantation and the clips are carefully removed. The hinge strength of the clip is measured by cutting off the latching mechanism at the tip of the clip and placing the cut end of the leg portion between the opposing grips of an Instron tensile tester. The grip has a steel surface. The force required to break the hinge is measured in Kg by moving the grip using an extension rate of 5 mm/min. The results of the test are shown in Table 2 below.

TABLE The above results clearly demonstrate an unexpectedly large improvement in the in vivo properties of the clips treated according to the invention. Having described the invention herein in terms of several specific embodiments, those skilled in the art will understand that
It will be apparent that modifications and variations to this invention are possible without departing from its spirit and scope.

[Brief explanation of drawings]

FIG. 1 is an enlarged perspective view of a ligation clip according to the invention. FIG. 2 is an enlarged perspective view showing the clip of FIG. 1 in a closed vessel position.
FIG. 3 is an enlarged perspective view of another surgical instrument according to the present invention. FIG. 4 is a perspective view of yet another surgical instrument according to the present invention. FIG. 5 is a cross-sectional view of the device of FIG. 4 in a closed wound position; 10: Ligation clip, 11, 12: Leg member, 1
3: Hinge part, 16: Blood vessel, 20: Fastener,
21: Staple, 22: Receiver.

Claims (1)

[Claims] 1 formula consisting of a polymer made from a monomer having
Density of at least 1.3845g/ ^cm3 and at least 43%
An injection molded surgical instrument having a crystallinity of . 2. The device of claim 1 having a crystallinity of at least 45%. 3. The device according to claim 1 or 2, wherein the device is a ligation clip. 4. The ligating clip of claim 3, comprising a pair of leg members joined at their proximal ends by a hinge portion. 5. The ligation clip of claim 4, wherein the distal end of the leg member includes a hooking means. 6 (a) Drying the injection molded device at a temperature below 30°C to remove substantially all moisture from the device; and (b) Drying the device at a temperature between 50 and 90°C without constraining the dried device. for at least 7 hours in a dry inert atmosphere, thereby improving the strength and functional integrity of the device. A method of treating an injection molded surgical device comprising a polymer made from a monomer having 7. The method of claim 6, wherein the device is a ligation clip. 8. Heat the dry utensils to a temperature of 80-85℃,
A method according to claim 6. 9. Claim 6 or 8, wherein the inert atmosphere is a nitrogen atmosphere containing substantially no moisture.
The method described in section.