U.S. patent number 3,620,218 [Application Number 04/852,617] was granted by the patent office on 1971-11-16 for cylindrical prosthetic devices of polyglycolic acid.
This patent grant is currently assigned to American Cyanamid Company, Stamford, CT. Invention is credited to Edward Emil Schmitt, Rocco Albert Polistina.
United States Patent |
3,620,218 |
|
November 16, 1971 |
CYLINDRICAL PROSTHETIC DEVICES OF POLYGLYCOLIC ACID
Abstract
Polyhydroxyacetic ester, also called polyglycolic acid (PGA),
has surgically useful mechanical properties as a solid prosthesis,
such as reinforcing pins, screws, plates, or cylinders. On
implantation, in living mammalian tissue, the polyglycolic acid is
absorbed, and replaced by living tissue.
Inventors: |
Edward Emil Schmitt (Norwalk,
CT), Rocco Albert Polistina (Port Chester, NY) |
Assignee: |
American Cyanamid Company,
Stamford, CT (N/A)
|
Family
ID: |
27406117 |
Appl.
No.: |
04/852,617 |
Filed: |
August 25, 1969 |
Current U.S.
Class: |
606/154; 606/155;
623/1.1 |
Current CPC
Class: |
C08L
67/04 (20130101); A61B 17/11 (20130101); A61L
31/06 (20130101); D01F 6/625 (20130101); A61L
31/06 (20130101); A61B 2017/00004 (20130101) |
Current International
Class: |
A61B
17/11 (20060101); A61L 31/06 (20060101); D01F
6/62 (20060101); A61L 31/04 (20060101); A61B
17/03 (20060101); A61F 13/15 (20060101); A61F
13/20 (20060101); A61F 13/00 (20060101); A61B
17/00 (20060101); A61b 017/11 () |
Field of
Search: |
;128/334,335.5
;3/DIG.1 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Dalton L. Truluck
Attorney, Agent or Firm: Samuel Branch Walker
Parent Case Text
CROSS-REFERENCES
This application is a continuation-in-part of application Ser. No.
608,086, Jan. 9, 1967 now U.S. Pat. No. 3,463,158, Aug. 26, 1969,
"Polyglycolic acid Prosthetic Devices" and Ser. No. 320,543, filed
Oct. 31, 1963 now U.S. Pat. No. 3,297,033, Jan. 10, 1967, "Surgical
Sutures."
Claims
We claim:
1. An absorbable prosthesis for the anastomosis of vessels in the
tissue of a living mammal consisting essentially of a hollow
cylinder of polyglycolic acid, having an inner diameter
approximately the same as the inner diameter of the subject vessel,
and a smooth outer surface of a diameter which is insertable in
said vessel when stretched, whereby one end of a vessel from
traumatic or surgical severance may be emplaced over each end of
said cylinder, and fixedly positioned thereon, said cylinder being
open to and permitting the flow of body fluids, and being
absorbable by living mammalian tissue within a few weeks.
2. The absorbable prosthesis of claim 1 in cooperative
configuration with at least one circular cooperative clamp, whereby
in assembled relationship, with a vascular vessel end on each end
of said cylinder, the vascular vessel ends are uniformly positioned
and retained on said cylinder, tightly enough to avoid substantial
slippage, and loosely enough to permit circulation into the vessel
ends, and hence avoid necrosis.
3. The absorbable prosthesis of claim 2 in which the said
cooperative clamp is a single split ring, with inward tension
sufficient to hold the ends of said vascular vessels, when
positioned over said vessels in place over said hollow
cylinder.
4. The absorbable prosthesis of claim 2 having two circularly bent
rod clamps, said clamps having radii of curvature such that the
vascular vessels are held against the hollow cylinder with
approximately uniform pressure, around the periphery of said
cylinder sufficiently tight to retain the vascular vessels during
regeneration, but loosely enough to avoid necrosis.
5. A method of anastomizing two vessels in living mammalian tissue
comprising inserting one end of a hollow cylinder of polyglycolic
acid having an inner diameter of approximately the inner diameter
of one of the vessels in the end of each of the vessels, so that
the ends of the vessels abut, and fastening the ends of the vessels
in abutting relationship over said cylinder of polyglycolic acid,
said cylinder being open to and permitting the flow of body fluids,
and being absorbed by said living mammalian tissue within a few
weeks.
6. The method of claim 5 in which the ends of the vessels are
fastened in abutting relationship by suturing the ends together.
Description
FIELD OF INVENTION
This invention relates to absorbable surgical structural elements
of polyhydroxyacetic ester hereafter called polyglycolic acid
(PGA).
PRIOR ART
The use of submucosal tissue and ribbons therefrom internally is
described in such patents as U.S. Pat. No. 2,167,251, Rogers,
"Surgical Tape of Submucosa Tissue," July 25, 1939, U.S. Pat. No.
2,143,910, Didusch, "Ribbon Gut and Method of Using the Same," Jan.
17, 1939, and U.S. Pat. No. 2,127,903, Bowen, "Tube for Surgical
Purposes and Method of Preparing and Using the Same," Aug. 23,
1938.
U.S. Pat. No. 3,155,095, A. M. Brown "Anastomosis Method and Means"
shows an internal and external absorbable coupling for the joining
of vascular vessels.
SUMMARY
Definitions in the textile trades are frequently somewhat
ambiguous. For purposes of the present application, certain terms
are defined:
A "filament" is a single, long, thin flexible structure of a
nonabsorbable or absorbable material. It may be continuous or
staple.
"Staple" is used to designate a group of shorter filaments which
are usually twisted together to form a longer continuous
thread.
An absorbable filament is one which is absorbed, that is digested
or dissolved, in living mammalian tissue.
A "thread" is a plurality of filaments, either continuous or
staple, twisted together.
A "strand" is a plurality of filaments or threads twisted, plaited,
braided, or laid parallel to form a unit for further construction
into a fabric, or used per se, or a monofilament of such size as to
be woven or used independently.
A "solid prosthetic device" is a thin solid sheet, or plate, or
tube, which may be split, or bar, or nail, or screw, or pin or
other solid shape which has inherent mechanical strength in
compression, bending and shear to act as a solid discrete surgical
reinforcing element, and has at least one dimension greater than 2
millimeters, and which may have a dimension as great as about 200
millimeters, or as required, to fit into or adjacent to and furnish
mechanical support and reinforcement to a bone, or bones, or gland,
or organ, for support during a healing process.
The size and shape of the prosthetic devices, or protheses, is
controlled by usage. For example, in the human body, in the case of
a bone fracture, a pin is used to reinforce a bone, and is of such
size as to be a tight driving fit into a central portion of the
bone, or a hole drilled into a bone. Such a pin can be from about
1/16-inch diameter and 3/8-inch length for finger bones, or for
children, up to 1 1/4-inch diameter and 6-inch length to reinforce
the femur, or thigh bone of large adult humans, or even larger for
valuable race-horses or other mammals.
The support may be in part directive of growth, as for example in
nerve tissue, which grows slowly, and as a result has regeneration
impaired by the more rapid growth of scar tissue which can block
the growth of the nerve tissue. With a wraparound sheath of PGA
sheet, or a split or solid tube used to support, place, hold and
protect; regeneration of nerve tissue and function is greatly
aided. Other factors may inhibit regeneration of nerve tissue or
function, but with the exclusion of scar tissue, such other factors
may be separately treated. PGA is particularly useful in splicing
nerves because PGA is completely dissolved in tissue and leaves
minimal or no residual scar tissue from the PGA.
For different purposes and in different types of tissue the rate of
absorption may vary but in general an absorbable prosthesis should
have as high a portion of its original strength as possible for at
least 3 days, and sometimes as much as 15 days or more, and
preferably should be completely absorbed by muscular tissue within
from 45 to 90 days or more depending on the mass of the cross
section. The rate of absorption in other tissues may vary even
more.
In common with many biological systems, the requirements are not
absolute and the rate of absorption as well as the short-term
strength requirement varies from patient to patient and at
different locations within the body, as well as with the thickness
of the section of PGA.
The PGA may be formed as tubes or sheets for surgical repair and
may also be spun as thin filaments and woven or felted to form
absorbable sponges or absorbable gauze, or used in conjunction with
other compressive structures as prosthetic devices within the body
of a human or animal where it is desirable that the structure have
short term strength, but be absorbable. The useful embodiments
include tubes, including branched tubes or Tees, for artery, vein
or intestinal repair, nerve splicing, tendon splicing, sheets for
tying up and supporting damaged kidney, liver and other intestinal
organs, protecting damaged surface areas such as abrasions,
particularly major abrasions, or areas where the skin and
underlying tissues are damaged or surgically removed.
The medical uses of PGA include, but are not necessarily limited
to:
A. Pure PGA 1. solid Products, molded or machined a. Orthopedic
pins, clamps, screws and plates b. Clips (e.g., for vena cava) c.
Staples d. Hooks, buttons and snaps e. Bone substitute (e.g.,
mandible prosthesis) f. Needles g. Nonpermanent intrauterine
devices (antispermocide) h. Temporary draining or testing tubes or
capillaries i. Surgical instruments j. Vascular implants or
supports k. Vertebral discs l. Extracorporeal tubing for kidney and
heart-lung machines 2. Fibrillar Products, knitted or woven,
including velours a. Burn dressings b. Hernia patches c. Absorbent
paper or swabs d. Medicated dressings e. Facial substitutes f.
Gauze, fabric, sheet, felt or sponge for liver hemostasis g. Gauze
bandages h. Dental packs 3. Miscellaneous a. Flake or powder for
burns or abrasions b. Foam as absorbable prosthesis c. Substitute
for wire in fixations d. Film spray for prosthetic devices
B. PGA in Combination with other Products 1. Solid Products, molded
or machined a. Slowly digestible ion-exchange resin b. Slowly
digestible drug release device (pill, pellet) c. Reinforced bone
pins, needles, etc. 2. Fibrillar Products a. Arterial graft or
substitutes b. Bandages for skin surfaces c. Burn dressings (in
combination with other polymeric films.)
The synthetic character and hence predictable formability and
consistency in characteristics obtainable from a controlled process
are highly desirable.
The most convenient method of sterilizing PGA prostheses is by heat
under such conditions that any micro-organisms or deleterious
materials are rendered inactive. A second common method is to
sterilize using a gaseous sterilizing agent such as ethylene oxide.
Other methods of sterilizing include radiation by X-rays, gamma
rays, neutrons, electrons, etc., or high-intensity ultrasonic
vibrational energy or combinations of these methods. The present
materials have such physical characteristics that they may be
sterilized by any of these methods.
PGA can be considered as essentially a product of polymerization of
glycolic acid, that is hydroxyacetic acid, which in simplified form
is shown by the equation:
Preferably n is such that the molecular weight is in the range of
about 10,000 or more. Above 500,000 the polymer is difficult to
mold.
In these molecular weight ranges the polymer has a melt viscosity
at 245.degree. C. of between about 400 and about 27,000 poises.
Because the PGA is from a synthetic and controllable source, with
the controlled molecular weight and controlled small percentage of
comonomer, the absorbability, stiffness, and other characteristics
can be modified.
Among several methods by which PGA can be prepared, one preferred
route involves the polymerization of glycolide, the cyclic dimeric
condensation product formed by dehydrating hydroxyacetic acid.
During polymerization of glycolide, the ring is broken and
straight-chain polymerization occurs.
Small quantities of other materials may be present in the chain, as
for example, d,1-lactic acid, its optically active forms, homologs,
and analogs. In general plasticizers tend to interfere with
crystallinity, orientation, etc. and weaken the prosthesis but are
useful for sponges and films. Other substances may be present, such
as dyes, antibiotics, antiseptics, anaesthetics, and antioxidants.
Surfaces can be coated with a silicone, beeswax, and the like to
modify handling or absorption rate.
The polymerization of glycolide occurs by heating with or without a
catalyst, or may be induced by radiation such as X-rays, gamma
rays, electron beams, etc. Polymers may also be obtained by
condensing glycolic acid or chloraacetic acid with or without a
catalyst under a variety of conditions. Good moldable objects or
fibers are most readily obtained when the melt viscosity at
245.degree. C. is about 400 to about 27,000 poises.
Polyhydroxyacetic esters have been described in U.S. Pat. No.
2,668,162, Lowe, "Preparation of High Molecular Weight
Polyhydroxyacetic Ester," and U.S. Pat. No. 2,676,945, Higgins,
"Condensation Polymers of Hydroxyacetic Acid."
The processes described in the above two patents can be used for
producing PGA from which prostheses may be made. Additives such as
triphenylphosphite or Santo-Nox, a disulfide aromatic phenol, can
be added as color stabilizers.
DRAWINGS
FIG. 1 shows a spliced artery having an internal sleeve with
slightly tapered ends, with a sewn splice.
FIG. 2 is a cross section of a spliced artery having an internal
sleeve with expanded ends.
FIG. 3 shows a prosthetic sleeve formed of a unitary coupling of
solid polyglycolic acid with slightly expanding ends to aid in
holding a blood vessel about the sleeve.
FIG. 4, shows the sleeve of FIG. 12 in use in which an external
spring clip of solid polyglycolic acid holds the ends of the blood
vessel together.
FIG. 5 shows the sleeve of FIG. 12 in which two expandable annular
clips are used to hold the ends of the blood vessel
approximated.
PGA for the construction of the prostheses shown in the drawings
can be produced as set forth in the following examples, in which
parts are by weight, unless otherwise clearly indicated.
EXAMPLE 1
One hundred parts of recrystallized glycolide (melting point
85.0.degree. to 85.5.degree. C.) are intimately mixed with 0.02
part of methoxyacetic acid, 0.03 part of phenoldisulfide
(Santo-Nox), and 0.03 part antimony trifluoride. Separate glass
tubes are each charged with approximately 20 grams of the mixture,
deoxygenated by repeated evacuation and argon purging, then sealed
under vacuum and heated to 185.degree. to 190.degree. C. for 4 1/2
hours. On cooling a white opaque tough PGA is produced in a 97.5
percent yield with a melt viscosity at 245.degree. C. of 5,000
poises. The polymer is reheated and spun into filaments at a
temperature of about 230.degree. C. at a speed of about 150 feet
per minute. The filaments produced are cooled, then drawn at about
55.degree. C. When drawn to 5 times the original length a strong
tough filament is produced. The dry filaments are in condition for
use.
EXAMPLE 2
The polymer of the preceding example is formed into a plurality of
smaller filaments, seven of which are twisted into a
polyfilamentary strand, which is sterilized and used following the
techniques of examples 1.
Because it is a synthetic polymer the methods of forming are more
versatile than in starting with naturally occurring materials.
EXAMPLE 3
Into a suitable reaction vessel there is charged 400 parts of a
commercial glycolic acid which is then heated from room temperature
to about 200.degree. C. over a period of about 4 hours. When the
pot temperature has reached 185.degree. C., the pressure of the
system is reduced from atmospheric pressure to 15 mm. of Hg,
causing the water of condensation and/or esterification to distill
off. The residue is allowed to cool and is pulverized into about
280 parts of a powder which is then added in small increments to a
suitable pyrolysis chamber maintained at a temperature of about
250.degree.-285.degree. C. at a pressure of less than 15 mm. of Hg.
The distillate which weighed about 238 parts is dissolved in a
minimum amount of hot ethyl acetate, and after decolorizing and
purifying with active carbon, the distillate is recrystallized from
the above solution to provide 160 parts of product having a melting
point of about 82.5.degree.-84.0.degree. C. The infrared spectrum
confirms that the product is substantially pure glycolide.
The glycolide thus prepared is polymerized in the presence of an
alcohol free of nonbenzenoid unsaturation and free of any reactive
groups other than alcoholic hydroxy groups and in the presence of
SnCl.sub.2 .sup.. 2H.sub.2 O.
A heavy walled glass tube having a bore of about three-tenths inch
and sealed at one end is charged with 3 parts of the substantially
pure glycolide composition, 0.04 part of a 0.1 percent ether
solution of SnCl.sub.2 .sup.. 2H.sub.2 O (about 0.0013 percent of
SnCl.sub.2 .sup.. 2H.sub.2 O based on the weight of the
substantially pure glycolide composition), 0.0166 part of lauryl
alcohol (0.346 mole percent based on the moles of the substantially
pure glycolide composition), and a magnetic steel ball five
thirty-seconds inch in diameter. The tube is evacuated and purged
with argon. The tube is evacuated again to a vacuum of less than 1
mm. of Hg and the top is sealed. The reaction tube is placed in a
vertical position in a closed glass chamber throughout which
dimethyl phthalate is refluxed at 222.degree. C. The boiling point
of the dimethyl phthalate is controlled by decreasing the pressure
of the system. At periodic intervals after melting, the viscosity
of the reaction mixture is measured by raising the steel ball by
means of a magnet and measuring the rate of the fall of the ball in
sec./in. Ninety minutes after the melt is first achieved, the ball
drop time is 550 sec./in. or about 7,200 poises, and after 120
minutes, the ball drop time is 580 sec./in. or about 7,600
poises.
The PGA thus produced is spun into 0.002-inch diameter fibers and
used to form strands.
Additional PGA, similarly produced is used to form sheets, or
tubes. These are wrapped around nerves, traumatically severed, to
protect such nerves from invasive scar tissue growth, while the
nerve is regenerating.
Also the PGA so produced is fabricated into the prosthetic devices
shown in the drawings. The PGA may be moulded or machined or
extruded to a desired configuration.
In FIG. 1 is shown an artery 37 which is joined together over a
tapered end PGA tube 38 which forms a stent about which the ends of
the artery wall are joined by a suture splice 39. The tapered end
is easier to insert in the artery.
In FIG. 2 the artery walls 40 are joined together over a flared end
PGA tube 41 and the ends are joined by a suture splice 42.
FIG. 3 shows the flared end PGA tube 41.
In FIG. 4 is shown a blood vessel 43, the ends of which are each
separatedly placed over the end of a flared PGA tube and which
blood vessel is held in place with the ends adjacent to permit
healing by a PGA spring clip 44. PGA, such as produced in the above
example 3, shows an Izod impact strength of 0.14 ft.-lbs. per inch
width or greater. It may be heated and formed into a desired shape
which shape is retained on cooling, and by shaping as a flat spring
clip, can be used to hold together the walls of a blood vessel 43
until natural regeneration takes place.
In FIG. 5 is shown a similar splice of a blood vessel 45 but in
which the ends are held together by an annular clip 46 of molded
PGA. Such annular clips are well known for the attachment of
radiator hoses to radiators in automobiles and the attachment of
other flexible tubing to connectors. By a suitable choice of
diameter and shape, as is well known in the industry, the radial
compression at all points about the periphery may be caused to be
approximately uniform and within a desired range. This is important
in the splicing of blood vessels as it is desired to hold the blood
vessel in position during regeneration, but yet not hold the
vessels so tightly that necrosis sets in because of an impaired
blood supply to the vessel walls.
While disclosed primarily for blood vessels, or vascular vessels,
because jointure of such vessels is of greatest interest at
present, obviously the same techniques and hollow splice cylinders
can be used on any of a variety of vessels in the body of man or
animals. Such tubes include fallopian tubes, spermatic ducts, bile
ducts, ureters, sinus tubes, eustachian tubes, tear ducts, or for
absorbable drain tubes in body cavities, or where a splice or
joindure is required in any body tube. The size of the hollow
cylinder is preferably such that the lumen, or internal diameter is
about that of the tube being joined. The ends of the cylinder are
conveniently tapered, so that the ends are readily insertable in
the body tube, and for blood vessels so that a minimum of tubulence
is induced in flowing blood, and hence thrombus formation is
minimized. The PGA cylinder appears to be essentially
nonthrombogenic.
The splice PGA cylinder normally is of uniform diameter, as usually
the ends of the vessel to be spliced are the same. The diameters
may be made different to join vessels of different sizes as may
occur where a splice is to be made between vessels not normally
joined. T- or Y-joints can be formed by molding or machining, with
the various openings of a desired size, with the PGA protheses to
be completely covered by the vessel walls. As the PGA protheses is
absorbed, the vessel walls must grow together without defects.
Also because of the tremendous strength of the solid PGA, a
surgical needle can be formed on the end of a PGA suture by either
fusing the PGA of the suture, or molding additional PGA onto the
suture end, the needle being bent and pointed as may be surgically
preferred for a specific surgical procedure. The ends or edges of
monocomponent or bicomponent fabrics containing PGA may be rendered
rigid by moulding such edges, with or without additional solid PGA
to a desired configuration. It is often easier to insert and retain
a flexible fabric prosthetic tube if the end of the tube is of a
size and shape to be inserted into the severed end of a vessel.
The drawings above are illustrative only of embodiment of the
present invention in which various prosthetic devices are
incorporated into the human body to aid impaired functions of
natural elements. From the above drawings and descriptions, it will
be obvious to those skilled in the art that many other
modifications may be adapted for particular injuries or ills to
which the flesh is heir.
The finding that polyglycolic acid, abbreviated PGA, is absorbable
in living tissue, and has marked mechanical strength, as a fiber or
solid, including sheet, and hence can be used as an element in, or
as, a surgical prosthesis, is most unexpected and
unpredictable.
Following the method set forth in the American Society for Testing
and Materials, 1969 Books of Standards, Part 27, Plastics--General
Methods of Testing, Nomenclature, ASTM, 1916 Race St.,
Philadelphia, Pa. 19103, May 1969, procedure 709-66 at page 303 to
310, (procedure B); a flexure strength of about 40,000 pounds per
square inch and a flexure modulus of 1.2 to 1.4.times.10.sup.6
pounds per square inch is developed by the solid bars of PGA. For
an unfilled plastic these values are spectacularly high. It is even
more remarkable that such high-strength values are developed by a
polymer that is absorbable by living mammalian tissue.
Catgut, or regenerated collagen has in the past been used for
tissue emplacement, but with collagen, as the collagen is absorbed,
a fibrotic tract replaces the collagen, so that in effect scar
tissue remains at the site of the emplanted collagen for many
years, in many instances for life. Some patients are allergic to
collagen. PGA is not a protein, has no amino acids, and has given
no evidence of allergic reactions in thousands of implants. With
the present PGA prostheses, the PGA is completely absorbed, and a
minimal or no trace of the inserted matter remains after a
comparatively short period. This complete absorption, without
residual fibrotic tissue, is unique, and an important contribution
to surgery.
* * * * *