FR2510411A1 - RETICULATED POLYDIOXANONE SURGICAL APPARATUS AND PROCESS FOR PRODUCING THE SAME - Google Patents

Abstract

THE PRESENT INVENTION RELATES TO A THERMALLY SHAPED SURGICAL APPARATUS AND A PROCESS FOR ITS PRODUCTION. THIS IS A THERMALLY SHAPED SURGICAL APPARATUS, MANUFACTURED FROM CROSS-LINKED POLYDIOXANONE, AND HAVING A DENSITY OF AT LEAST 1.3845 GCM AND A CRYSTALLINITY OF AT LEAST 43. APPLICATION IN PARTICULAR TO SURGICAL LIGATURING FORCEPS.

Description

The present invention relates to surgical apparatus made of

  p-dioxanone polymers and more particularly molded surgical devices made of such polymers having improved behavior characteristics in vivo.

  It is well known that in surgical procedures

  In many cases, synthetic devices, that is to say devices made from foreign materials, are often implanted. Examples of such methods are found in surgery where tongs made of tantalum or stainless steel are used. Other metals to counteract bleeding by ligation of various blood vessels or other tubular organs during the surgical procedure In addition, in other surgical procedures, various other sticks, staples, forceps or metal foils for various media or for other reasons during a surgical act In most cases, these devices remain in the body of the patient for considerable periods of time, although in some cases they may be removed at a later date. later date or even rejected by the natural physiological function of the

human conps.

  For most of these metal surgical devices,

  although they may be safe from a medical point of view

  cal, it is desirable not to leave them in the body as they greatly disrupt postoperative procedures

  X-rays and the subsequent obtaining of a diagnostic image

  that of the patient Not only the metal

  distort the formation of X-ray images, but they

  the more recent images obtained by computerized axial tomography, as well as certain other

  new types of procedures for obtaining diag-

  It is therefore desirable that surgical appliances

  to be replaced by non-metallic biocompatible materials which do not have a disruptive effect on the new processes for obtaining diagnostic images It is even more desirable to manufacture medical devices, in many cases from absorbable polymers. so that once they have fulfilled the desired function, they are absorbed by the human body and therefore have no subsequent effect on obtaining diagnostic images etc. Devices made from absorbable polymers also prevent any long-term complication that may

  occurrence of the presence of a foreign body in the tissue.

  Surgical devices and polymers absorb

  The desired beads are described in more detail in US Patent No. 4,052,988 of October 11, 1977 and herein incorporated by reference.

  such a desirable surgical apparatus from these poly-

  absorbable mothers is described in the patent application

  filed by the same Applicant under No. 0288,274 to US A on the same date as the present application In this case, a method for producing a surgical apparatus molded from pdioxanone polymers is described. the method described in the aforementioned patent application have the strength and other properties desired for many surgical purposes, it is still important to further improve the strength, functional integrity, flexibility, and

  particularly the tactile and audible properties of

  These improved properties extend the potential use of the devices and improve their reliability, stability, and reliability.

  the in vivo behavior of such surgical devices.

  What the Applicant has discovered is a crosslinking or heat treatment process for thermally formed surgical devices made from the polymers of p-dioxanone, which improves the strength and functional integrity of the device while improving

  also the audible and tactile properties of the device.

  The audible and tactile properties of the device can be explained in more detail if it is understood that in many surgical procedures the surgeon works

  in a zone of limited vision By working in this way, the

  The advantage of the present forceps over the prior art forceps is that the surgeon can rely on touch and hearing to know when a

  Specific step of the surgical procedure has been completed.

  Thus, when closing a blood vessel with a latch type of clamp, the surgeon may not see this step and therefore rely on resistance to closure of the clamp (tactile property) or a click or snap when the The latch closes (audible property) It has been discovered that the present novel method unexpectedly improves these properties in surgical apparatus made from the polymers of p-dioxanone. The new method also produces a surgical apparatus having a duration of

  improved preservation in that the apparatus is more resistant

  both to the hydrolysis caused by residual moisture in

packaging.

  According to the invention, the present novel process for treating

  A thermally formed surgical apparatus made from p-dioxanone polymers to improve the two properties described above involves drying the thermally formed apparatus under nitrogen cleaning at a temperature not to exceed 300 ° C for a period of time. sufficient time to remove almost all the moisture from the apparatus The dried apparatus is heated in an atmosphere

  dry, inert, oxygen-free, preferably atmospheric

  nitrogen, at a temperature of 500 ° C. to 90 ° C. and preferably at a temperature ranging from 800 ° C. to 850 ° C. for

at least 7 hours.

  The new products resulting from the invention comprise

  thermally-formed surgical devices

  bricks made from p-dioxanone polymers having a density of at least 1.384 grams per cm and a crystallinity of at least 43% and preferably at least 45%. Figure 1 is an enlarged perspective view of a clamp

for ligatures according to the invention.

  FIG. 2 is an enlarged perspective view showing the

  Figure 1 forceps in place ligating a blood vessel.

  Figure 3 is an enlarged perspective view of a

  surgical apparatus still different according to the invention.

  FIG. 4 is a perspective view of a surgical apparatus

  still different according to the invention; and FIG. 5 is a section showing the apparatus of the

  Figure 4 in place and closing an injury.

  The new surgical apparatus of the invention are made from polymers composed of units of general formula

_C-CH 2-0-CH 2 -CH 2 -O

  _ _ x where x is the degree of polymerization giving the polymer

longed for.

  The polymer is prepared from a monomer having the following formula:

CH C = O

CH 1 =

CH 2 H 2

  Generally, the surgical apparatus of the invention

  are produced by injection molding techniques.

  A specific and preferred method of injection molding

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  is described in the patent application also filed by the same Applicant under No. 288,274 to the US at the same date and incorporated herein by reference. Although surgical devices are described as being made by injection molding, they may also be be made by compression molding or extrusion molding, etc. After molding, the polymers are dried to remove almost all the moisture in the molded article. The polymers are dried with a nitrogen cleaning at a temperature below 300 ° C. C so that almost all the moisture is removed for

  to reduce the possible hydrolysis of the absorbable polymer.

  Once the molded article is dried, it is placed in an atmosphere of an inert gas, dry, free of oxygen, preferably, and for the purpose of economy, nitrogen, although

  other dry inert gases can also be used.

  The molded article is heated in the dry inert atmosphere at a temperature of at least 500 ° C. but not exceeding 90 ° C.

  and preferably at a temperature ranging from 80 to 850 C

  for a period of at least 7 hours. It is preferable

  it is not subject to any constraints during this

  Heating ration The molded article is then packaged, sterilized, dried and ready for use Generally, the polymers used according to the invention are sterilized by ethylene oxide treatment as is known to those skilled in the art. It has been found that the method described above improves the strength of the various configurations used in

surgical apparatus.

  It not only improves the basic or initial resistance of the device, but it also reduces the importance

  the loss of resistance of the device with time in vivo.

  The present crosslinking process also improves the

  tactile and audible responses of surgical devices

  bribed according to the process and improve their hydro-

  so that the shelf life of the apparatus is considerably increased. It is believed that the present crosslinking process produces crystallites within the article.

  mold which increases its resistance to hydrolysis and improves

  the strength and functional integrity of the molded apparatus. The present new surgical devices made from polymers and copolymers of p-dioxanone have a density of at least 1.3845 g per cm It is absolutely necessary that the apparatus has this density to have the improved properties here In addition, the present new surgical devices have a crystallinity of at least

  minus 43% and preferably 45%.

  The crystallinity of the forceps is a measure of the resistance

  tance and functional integrity of the forceps

  X-ray is a convenient method for determining

  the importance and type of crystallinity in the forceps.

  X-ray crystallinity data are obtained by

  using a Phillips vertical gonometer with a mono-

  graphite crystal chrometer and a scintilla detector

  a tape recorder is used. Cu Ka radiation is used and a sample is mounted and processed using parallel geometrical focusing ("parafoeusing") The diagrams obtained for a sample are analyzed in order to know crystallinity and content

  amorphous by means of a Du Pont curve separator.

  With reference to the drawings, there are described certain specific types of surgical apparatus of the invention

  which can be manufactured by the process of the invention.

  Figure 1 shows a ligator clamp 10 This clamp is

  used to ligate a blood vessel during the course of

  The forceps comprises two branch elements 11 and 12 joined at their proximal end by a hinge section 13 The branches engage or latch at their distal ends 14 and 15 FIG. 2 shows the forceps of FIG. closed position closing the lumen of a blood vessel 16 The surgeon, when placing this clamp, must often place it in an area he can not see and it is therefore important that he can feel the resistance of the section articulated and the engagement mechanism; in other words, the tactile feedback he wants in the surgical apparatus. The surgeon also wants to hear an audible click.

  when the branch element moves away to catch the element

  FIG. 3 shows another thermally formed surgical apparatus. This apparatus is a two-piece fastener for closing wounds and the like. The clip includes a clip 21 and a receptacle 22 for

  the clip Figure 4 shows yet another heat device

  The apparatus includes a thin elongate section 26 with transverse pieces 27 disposed at each end of the elongated thin section using a suitable instrument. having a hollow needle to hold the apparatus, inserting the needle into the tissue and using the apparatus to close the wound, the elongate section 26 spanning the injured area and the transverse pieces 27 squeezing the sides

  opposite of the injured area as shown in Figure 5.

  Other medical devices contemplated in the invention are solid products such as orthopedic pins, flanges, screws and plates; fasteners, staples, hooks, buttons and clasps; bone substitutes like

  mandibular prostheses; needles; in-house devices

  uterine; various tutular ducts such as urethra, cystic canalos, etc .; surgical instruments, vascular implants, couplers or supports; and records

  vertebral and other similar devices.

  The in vivo resistance properties of chemical devices

  The remedies contemplated by the invention are extremely important.

  It is of critical importance that the surgical device retain its desired functional properties during

  extended periods of time when placed in an environ-

  where it is slowly absorbed, like the living tissue.

  The device must maintain its resistance in such an environment for a period of time sufficient to allow it to

  completing the desired task The new devices according to the invention

  have excellent in vivo properties as shown by

  in more detail the specific example that follows.

Example

  A number of injection-molded pliers are molded

  as is stated in the patent application belonging to the same applicant and filed simultaneously with the present under no. 288 274 to the E U -A The clamps have the configuration that

  Fig. 1a and are processed according to the invention.

  Claws are cleaned in two 15-minute baths of isopro-

  panol with stirring In the cleaning process, about 1 ml of isopropanol is used per clip The alcohol is discarded and a single layer of tongs is placed in a flat bundle and dried under a vacuum for 16 hours to remove the Alcohol 20 cleaned tweezers are removed, their density is determined and the resistance to opening is tested

  and the resistance of the clamp hinges.

  The density is determined using a column with

  Density prepared according to ASTM Method D-1505.

  (The gradient used goes from a density of 1.350 to 1.400 for

  cover the general range observed for the poly-

  dioxanone) Standard calibrated density floats are added

  darts to the column, one graduates in millimeters, and one leaves them

  sinking at various positions in the gradient column.

  We record the density and the position of each float of standard density We draw up the graph of the density opposite the position in the column and we highlight

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  a linear relation There are three clips in the colon

  density gradient and let them rest for 5

  at 10 minutes The position of the tongs is recorded.

  mines the average of the positions of the clamps The corresponding density of the clamp is determined by the linear relation

  from the density to the position in the column.

  The resistance of the hinge of the clamp is the force needed to break the clamp in the region of the hinge,

  and is determined as follows. The engagement mechanism is

  at the distal ends of the forceps and the cut ends of the limbs are placed in the opposing jaws of an Instron tensiometer The jaws are covered

  using a deformation speed of 5 mm / min.

  the jaws are removed and the force required is determined.

re to open the clamp in kg.

  The crystallinity of the clamp is measured as mentioned above.

  The remaining tongs are heat-treated by

  In a furnace Nitrogen was passed over the tongs 7,08 m 3 / min at room temperature. The temperature in the furnace was then raised to 850 ° C and maintained.

  this temperature with a nitrogen flow rate of 1.42 m 3 / minute.

  After 8 hours and 16 days, the tongs are removed and placed in a desiccator and

  transfers to an ambient vacuum for cooling purposes.

  Pliers are wrapped in sheet bags, with pliers per bag. Bags are sterilized with ethylene oxide.

  it is degassed and sealed in an atmosphere of dry nitrogen.

  The density and the crystallinity of the tongs are determined and the resistance to opening and the resistance of the hinges of the tongs is tested. The results of the experiments are

given in Table 1 below.

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Table 1

  No re 8:00 am

  ticulation culation culation% crystallinity 38 47 46 Density (g / cm 3) 1 3829 1 3876 1 3881

Resistance to opening

  ture (kg) 2 30 2 30 2 43 Hinge strength (kg) 1 73 2 13 2 14 Distinct distinct audible / tactile response As can be seen from the table above,

  treated tongs according to the invention have a larger crystal

  are more dense and have higher resistance

  to those of untreated forceps -

  A number of each type of clamp is tested; it is-

  to say non-crosslinked, crosslinked for 8 hours and crosslinked

  for 16 hours to determine their retention properties.

  Resistance in vivo In vivo resistance properties are determined as follows Clams containing packages of each batch are opened and pliers removed. Pliers are separated by attempting to proceed randomly in groups of ten Each group corresponds to an experimental range of hinge resistance. Special Long Evans rats, weighing 150 to 300 g, are acclimated for at least one week before the operation. All the rats are prepared for the operation, then

  they are anesthetized, and two clips are implanted in each rat.

  Pliers are implanted in the dorsal dorsal posterior left

  and right of the rat At the end of each period following the

  Five rats are sacrificed and the forceps are carefully removed. The hinge resistance of the forceps is determined by cutting the locking mechanism at the end.

2 2510411

  distal from the forceps and placing the cut ends of the limbs in the opposite jaws of an Instron tensiometer The jaws are coated with steel Using a deformation rate of 5 mm / minute the jaws are spread apart and the force required to determine break the

hinge in kg.

  The results of the tests are given in Table 2 below.

under.

Table 2

  Retention of hinge resistance (kg) Duration No 8 hours of 16 hours of implantation crosslinking crosslinking crosslinking Starting value 1.72 2.20 2.11 3 days 1.66 2.00 2.01 10 days 1.62 1.99 1.93 21 days 0.92 1.73 1.76 28 days O 1.18 1.50

  The results above clearly show the improvement

  Substantial and unexpected ration of in vivo properties

  pliers treated according to the invention.

  Since the invention has been described with certain specific embodiments, it must be apparent to those skilled in the art that various modifications and alterations can be made.

  of invention without departing from its spirit and scope.

Claims (14)

CLAIMS:   Thermally formed surgical apparatus made from a polymer prepared from a monomer of formula CH 2 CH 2 -   C z CH 2 said apparatus having a density of at least 1.3845 gram   per cubic centimeter and a crystallinity of at least 43%.   Thermally formed surgical apparatus made from a polymer having units of the formula: -C-CH -O -CH 2 -CH 2-O-   x o x is the degree of polymerization giving a thermally formable apparatus, said apparatus having a density   not less than 1.3845 grams per cubic centimeter at least 43% tallinity.   Apparatus according to claim 1 or claim 2   having a crystallinity of at least 45%.   4 Apparatus according to one of claims 1, 2 or 3   o The device is a ligating clamp.   The ligating clip of claim 4 comprising a pair of limbs connected at their proximal end by a hinge section.   6 ligating clamp of claim 5 o the ends   distal branches comprise engagement means.   Thermally formed apparatus of one of the claims   1 or 2 o the device is an injection molded device.   8 ligating clamp of one of claims 4 or 5 o   the clamp is an injection molded clamp.   9 Process for treating a thermal surgical apparatus   formed from a polymer prepared from a monomer of formula X 2 CH 2 CH 2 CH   wherein: (a) the thermally formed apparatus is dried at a temperature below 30 C to remove substantially all moisture from the apparatus; and (b) the dried apparatus is heated in a dry inert atmosphere at a temperature of 50 ° C. to 90 ° C. for at least 7 hours, which improves the strength and the functional integrity of the device.   Method of treating thermal surgical apparatus   formed from polymers having units of formula II -C-CH 2-0-CE 2-CH 2-0-   x o x is the degree of polymerization yielding a thermally formable polymer, wherein: (a) the thermally formed apparatus is dried at a temperature below 30 C to remove substantially all moisture from the apparatus; (b) the dried apparatus is heated in an inert atmosphere at a temperature of from 50% C to 900 C for a time sufficient to bring the crystallinity of the apparatus to   less 43% which improves the resistance and the integrity the device.   The method of claim 10 wherein the apparatus is heated   dried wire for at least 7 hours.   Method according to one of claims 9 or 10 o the   device is a ligating clamp.   13 Method according to one of claims 9 or 10 where one   heats the dried apparatus at a temperature ranging from 80% C to% C.   Method according to one of claims 9, 10 or 13 o   the inert atmosphere is a nitrogen atmosphere practically devoid of moisture.   Method according to claim 9, 10 or 13 o   the device is an injection molded device.