JPS5827548A - Annealed polydioxane surgical instrument and production thereof - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

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 in many and various surgical procedures the implantation of synthetic devices, ie, devices made of IA material, is very frequent. An example of such a procedure is surgery that uses tantalum or stainless steel or other metal clips to control bleeding by ligating 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 considerable period of time, in some cases it is necessary to remove them at some time thereafter or to be rejected by the human body's natural physiological functions. Even.

In many cases, these metal instruments, although not causing any harm from a medical standpoint,
It is desirable not to allow it to remain in the human body since it would seriously interfere with imaging for treatment and subsequent patient diagnosis.

Metallic materials not only interfere with X-ray imaging, but also modern computerized 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, therapeutic devices made of absorbable polymers are used so that they are not absorbed by the human body after performing their desired function and thus do not affect subsequent diagnostic imaging, etc. It is further desirable to manufacture. 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 U.S. Pat. No. 4.052. ? No. 88 discloses this in further detail. Specific methods for the manufacture of such surgical instruments made of these absorbable polymers are disclosed in co-pending patent applications filed on the same date as this specification. This patent application describes a method for manufacturing molded surgical instruments from polymers of p-dioxanone.

The surgical instrument manufactured according to the method described in the above patent application is
Although possessing the strength and other properties desired for many surgical procedures, the strength, functional integrity, flexibility, and especially tactility and audibility of surgical instruments made from these polymers are Further improvements are still important. These improved properties expand the possible applications for the instruments and also improve the reliability, reliability, and reliability of such surgical instruments.
Improves stability and in vivo behavior.

What we have discovered is that thermally formed surgical instruments made from polymers of p-dioxanone increase the strength and functional integrity of the instrument while also improving the audibility and tactility of the instrument. This is a method of tempering or heat treatment. 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. When working in this way, the advantage that the clip according to the invention has over conventional clips is that the surgeon can rely on tactile and auditory sensations to know when a particular stage of the surgical procedure has been completed. That's what it means. 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 burr 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 thermally formed surgical instruments made of polymers of p-dioxanone to improve both of the properties mentioned above consists of:
The thermally formed 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. Keep dry instruments free of oxygen.
5 in an inert dry atmosphere, preferably an atmosphere of nitrogen.
Heat at a temperature of 0-90°C, preferably 80-85°C, for at least 7 hours.

The novel product of the invention thus obtained has at least 15
A thermally formed round surgical instrument made of a polymer of p-dioxanone having a density of 84.9/ffl and a crystallinity of at least 45≦, preferably at least 45%.

The novel surgical instruments of the present invention are made from a polymer consisting of units having the general formula O where X is the degree of polymerization in the desired polymer. Manufacture.

Generally, the surgical instruments of the present invention are manufactured by injection molding processes. A specific and preferred method of injection molding is described in co-filed patent application Ser. here,
Although described as manufacturing surgical instruments by injection molding, these instruments can also be manufactured by compression molding, extrusion molding, and the like. Drying the shaped polymer removes substantially all of the moisture in the shaped product. 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 shaped product, it is placed in an atmosphere of a dry, inert, oxygen-free gas, preferably nitrogen for economy, although inert gases other than nitrogen may be used. . Products molded in a dry, inert atmosphere,
Temperature of 50°C to 90°C, preferably 80 to 85°C
Heat for at least 7 hours at a temperature of . During this heating operation, the device is preferably placed under non-constrained conditions.

The shaped product is then packaged, sterilized, dried, and ready for use. Generally, the polymers used in accordance with the present invention are sterilized by treatment with ethylene fluoride, 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 treatment according to the present invention includes:
Furthermore, improving both the tactile and audible responses of surgical instruments produced by the method of the present invention and increasing their hydrolytic resistance greatly improves the shelf life of the instruments. 4 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.

Novel surgical instruments of the present invention made from polymers and copolymers of p-dioxanone, at least t3845p/α1
It has a density of It is essential that the device has this density in order to have the improved properties mentioned above. Furthermore, the novel surgical instrument of the present invention has a degree of tying of at least 43%, preferably 45%.

The crystallinity of the clip is a measure of its strength and functional integrity. X@ diffraction is a convenient method for determining the location and type of crystallization in a clip. Xls crystallinity data are obtained using a Philips vertical goniometer equipped with a graphite crystal monochromator and a scintillation detector connected to a strip chart recorder. (Using 'u[s-rays and mounting the sample, measurements are taken using parafocusing geometry. The diffractogram obtained for the sample is analyzed for crystallinity and amorphous content using a DuPont curve analyzer. do.

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 clip 10 for ligation. 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 is hooked and fixed at both ends 14 and 15. 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. This 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 includes a thin elongated section 26;
It consists of horizontal bars 27 located at both ends. Using a suitable tool with a hollow needle to hold the device, insert the needle into the tissue and use the device to create a long section 26 across the wound area and the wound, as shown in FIG. The wound is closed by crossbars 27 that grip both sides of the area.

Other surgical instruments within the scope of the invention include solid articles such as orthopedic bottles, 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 insertion tubes, connective wire supports; and vertebropelvises, and others. This is a similar device.

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 wire according to the present 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. 1. Stir these clips in isopropyl alcohol.
Wash twice for 5 minutes.

In the cleaning process, approximately 111
Use the isoproper tool d. Pour off the alcohol, place one layer of clips in a flat dish and dry under vacuum for 16 hours to remove the alcohol.

Twenty cleaned clips are removed, their density measured and tested for opening and hinge forces.

Density is measured using a density gradient column prepared according to the method of Human 8TM D-1505. (The density gradient used spans densities from 1350 to t400, encompassing the typical range observed for polydioxanone clips). A standard calibrated density float is placed in a millimeter scale 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 Kara people 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. The grip is moved using an extension rate of 5 sec/min and the force required to break the hinge is measured in q.

Clip opening force 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 has a diameter of 4 cm and a length of 1781111
11 thickness is 1076m.

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 grasper using an extension rate of 5 sa 7 minutes and measure the force required to open the clip in units of force.

The crystallinity of the clip is determined as described above.

Place the remaining clip in a heater and heat treat it.

Pass nitrogen over the clips at a rate of 2.50 cubic feet per minute at room temperature. The temperature in the heater is then increased 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 and placed in a desiccator and cooled under vacuum. Place 10 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.

1st surface tempering 8 hours 16 hours None Tempering Tempering crystallinity, % 58 47 46
Density (y/cc) 13829 t5B76
15881 Opening strength Kf) 2,30
2.30 2.43 Hinge strength - 1752,1
32,14 Audible/Tactile Response None Significant Significant As can be seen from the table above, the clips treated according to the present invention have a greater degree of crystallinity, are denser and have improved strength than the untreated clips. It has a certain quality.

The clips for the untempered, 8-hour tempered, and 16-hour tempered clips are shown below.
Test for strength retention in vivo. In-vivo strength properties are measured as follows.

Open the package containing the clips from each loft and remove the clips. These clips are divided into groups of 10 each without any obvious bias. Each group corresponds to one interval of the joint strength test. Specialized Long-Evans rats weighing 150-500 Ii are allowed to acclimate for at least one week before surgery.

After each mouse is prepared for surgery and anesthetized, two clips are implanted into each mouse. Graft the clip into the dorsal skin of the right and left buttocks of the mouse. Five rats 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 in-plane tensile tester. The grip has a steel surface. Using an extension rate of 5-7 minutes, move the grip and measure the force required to break the pair in q.

The results of the test are shown in Table 2 below.

Table 2: Pair strength retention (Kp) 3 days 166 2. Mouth 0
2.0110 days 162
'199 19321 days [192173
1715 28th Ot18 1.50 The above results clearly demonstrate an unexpectedly large improvement in the in vivo properties of the clips treated according to the invention.

Although this invention has been described herein, including several specific embodiments, those skilled in the art will recognize that modifications and changes may be made thereto without departing from the spirit and scope of the invention. One thing should be obvious.

[Brief explanation of the drawing]

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. Figure 5 is a cutaway showing the instrument of Figure 4 in the closed wound position;
kJli! ! It is I. 10: Ligation clip, 11, 12: Leg member, 15: Hinge part, 16: Blood vessel, 20: Fastener, 21: Staple, 22: Receiver

Claims (1)

Claims: A polymer made from monomers having formula 1, comprising at least t! +845p/am” density and at least 43%
A thermally formed surgical instrument having a crystallinity of . where X is the degree of polymerization to give a thermally moldable device, consisting of a polymer having units of at least t3845
11/cs" and a crystallinity of at least 43%. & A device according to claim 1 or 2 having a crystallinity of at least 45%. 4. 5. The device according to claim 1, wherein the device is a ligation device. Ligation clip. 6. The ligation clip according to claim 5, wherein the tip of the leg member is characterized by a hooking means. l. The ligation clip according to claim 1 or claim 2, wherein the device is an injection molded device. A thermally formed device. a. A ligation clip according to claim 4 or 5, wherein the clip is an injection molded clip. 9(a) Drying the thermally formed device at a temperature below 30°C. and (b) heating the dried device at a temperature of 50 to 90° C. for at least 7 hours in a dry inert atmosphere, thereby increasing the strength and functional integrity of the device. A method for treating a thermally formed surgical instrument comprising a polymer made from a monomer having the formula: 1α (m) Drying the thermally formed surgical instrument at a temperature below 50°C. removing substantially all moisture from the device by; (b) subjecting the dried device to an inert atmosphere at a temperature of 5° to 90° C. for a period sufficient to increase the crystallinity of the device to at least 43%; from a polymer having the units of where X is the degree of polymerization giving a thermally moldable polymer. 11. The method of claim 10, wherein the dry instrument is heated for at least 7 hours. 12. The method of claim 10, wherein the instrument is a ligation clip. The method according to item 10. 15. Heating the dry instrument to a temperature of 80 to 85°C.
14. The method according to claim 9.10 or claim 13, wherein the inert atmosphere is a substantially moisture-free nitrogen atmosphere. 15. The method of claim 9.10 or ti15, wherein the device is an injection molded device.