Methods of forming bioabsorbable objects from polyvinyl alcohol

Method for forming polyvinyl alcohol (PVA) into surgical elements include forming a mixture of PVA and water into a film by vacuum pressing with a first force, heating, applying a second force two to two hundred times the firs force, drying the film to remove water to a content of less than about 10% by weight based on the weight of the film, and molding the film into a desired shape.

FIELD OF THE INVENTION 
This invention relates to methods of preparing bioabsorbable objects. More 
particularly, this invention relates to methods of preparing medical 
devices or surgical elements from polyvinyl alcohol. 
BACKGROUND OF THE INVENTION 
Polyvinyl alcohol (PVA) is a polyhydroxy polymer and, consequently, a 
water-soluble synthetic resin having the general formula: 
##STR1## 
The largest application for PVA is in textile sizing. Other applications 
for PVA include its use in adhesives, paper coatings and as a 
polymerization aid. PVA has also been used as a component in soluble or 
bioabsorbable medical devices or surgical elements. 
Various methods are described in the prior art for incorporating PVA into a 
medical device or forming such a device from PVA. For example, chemical 
attachment of a PVA coating to vascular protheses is described in U.S. 
Pat. No. 4,743,258. 
Injection molding of PVA and modified PVA compounds has been suggested to 
form tampon applicators (U.S. Pat. No. 5,002,526) and components of bone 
graft implants (U.S. Pat. No. 4,863,472). 
Solvent casting of PVA has been suggested for forming: a subsidiary device 
for suturing an intestine (U.S. Pat. No. 4,705,039); a bioerodible ocular 
device (U.S. Pat. No. 3,960,150); and a PVA-gel support pad from 
cross-linked PVA. 
U.S. Pat. No. 3,922,434 describes a number of ways of applying a water 
soluble polymer such as PVA, to a paper substrate or carrier. One way of 
adding the polymer in connection with the manufacture of the carrier is to 
mix cellulose powder and pulverulent water soluble polymer, adding a small 
amount of water and then compression molding the mixture (See U.S. Pat. 
No. 3,922,434, column 4, lines 51-56). 
PVA films oriented in two orthogonal directions may be produced in 
accordance with the methods described in U.S. Pat. No. 4,124,677. 
The extrusion of a PVA rod which is chopped into pellets and then injection 
molded is described in U.S. Pat. No. 3,882,196. 
In general, there are several problems associated with the molding of PVA. 
PVA is not easily molded as received from a supplier due to the fact that 
its melting temperature is above its degradation temperature. Therefore, a 
plasticizing agent, such as water, must be added. Only small amounts of 
water need to be added for the plasticizing effect to be experienced. 
However, adding only small amounts of water makes it very difficult to 
produce a homogenous mixture. A non-homogenous mixture results in an 
unacceptable product due to, among other things, non-uniform strength. 
Unfortunately, adding relatively large amounts of water causes the 
generation of numerous voids during the manufacture of a PVA film or 
object, again resulting in an unacceptable product. 
Accordingly, it is an object of this invention to provide an improved 
method of forming soluble or bioerodible items from PVA. 
It is a further object of the invention to provide a PVA molding process 
which overcomes the difficulties associated with known PVA molding 
techniques. 
SUMMARY OF THE INVENTION 
Bioabsorbable objects are produced in accordance with the present invention 
by preparing a mixture of polyvinyl alcohol and water and forming a film 
from the mixture by: i) applying a first, relatively low force to the 
mixture; ii) heating the mixture to a temperature of at least about 
100.degree. C. but below the degradation temperature of the polyvinyl 
alcohol; and iii) applying a second, relatively high force to the heated 
mixture. Water is then removed from the film and the film is molded into a 
predetermined form. 
In another aspect, the present invention involves forming a mixture of PVA 
and water by adding water to PVA in small increments until the PVA/water 
mixture contains from about 15% to about 50% water by weight of the 
mixture. This mixture is then formed into a film. Water is removed from 
the film. The dried film is then molded into a desired shape. 
DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Polyvinyl alcohol suitable for use in the present invention may be of any 
molecular weight. Preferably, medium to high molecular weight PVA is used. 
More preferably, PVA having a molecular weight of 78,000 to 80,000 may be 
utilized. Additionally, the level of hydrolysis of the PVA is not narrowly 
critical. A preferred hydrolysis level for the PVA is about 88 percent. It 
should be understood, of course, that various combinations of molecular 
weight and hydrolysis may be used to produce a product having a desired 
combination of physical properties. Suitable PVA is available under the 
tradename ELVANOL from DuPont Polymers, Wilmington, Del. and under the 
tradename AIRVOL from Air Products and Chemicals, Inc., Calvert City, Ky. 
The first step in the methods of the present invention is forming a mixture 
of PVA and water. Preferably, the PVA/water mixture will contain from 
about 15% to about 50% by weight of water. Most preferably, the mixture 
will contain from about 25% to about 35% water. 
The water may be added in any known manner. Preferably, the water is added 
in small increments while stirring the PVA vigorously. This will provide a 
substantially homogenous mixture of PVA and water having a dough-like 
consistency. 
Optionally, once the PVA/water mixture is formed, a portion of the water 
may be removed. This can be accomplished by subjecting the mixture to 
reduced pressure, with or without heating. If this drying step is 
employed, it is preferred that the water level in the mixture remain 
between about 10% and about 25% by weight of the mixture. 
The mixture is then formed into a film. Any known method may be used to 
form the film. Preferably, the film is formed by: i) applying a first, 
relatively low pressure to the mixture; ii) heating the mixture to a 
temperature of at least about 100.degree. C. but below the degradation 
temperature of the PVA; and iii) applying a second, relatively high force 
to the heated mixture. The first, relatively low force may range from 
about 250 pounds to about 5000 pounds. Preferably the first, relatively 
low force is between about 500 and about 1500 pounds. The second, 
relatively high force applied to the mixture may range from about 10,000 
pounds to about 50,000 pounds. Preferably, the relatively high force is 
between about 25,000 and 35,000 pounds. The second relatively high force 
is applied to the mixture once it has been heated to a temperature between 
100.degree. C. and the degradation temperature of the plasticized PVA. The 
second force is preferably applied to the mixture at a temperature between 
about 130.degree. and 190.degree. C. The high pressure is maintained for a 
period of about 0.5 to about 30 minutes and is preferably maintained on 
the mixture during the cool down period. Cool down may be accomplished by 
any known technique, such as by spraying water mist or streaming water 
onto the press for anywhere from about 0.5 to about 30 minutes or longer. 
In a particularly preferred embodiment the film is formed in a vacuum 
press. In this case, the chamber of the vacuum press may be evacuated to a 
pressure of about 1 to about 600 mm Hg, and preferably to a pressure of 
about 10 to 100 mm Hg. 
Once the film is formed, water is removed from the film. The removal of 
water may be accomplished in any known manner. Preferably, the film is 
placed into a vacuum oven for a period of time. The parameters to which 
the vacuum oven is set may vary widely, but typically range from 1 to 600 
mm Hg and 35.degree. to 150.degree. C. The duration of this drying step 
will vary depending upon the settings of the vacuum oven but may typically 
range from about 0.5 to as much as 24 hours or more. Preferably, water is 
removed from the film until water constitutes from about 2 to about 10% by 
weight of the film. 
The next step in the methods of this invention is molding the film into a 
desired shape. Molding of the film into the final shape may be carried out 
in a vacuum press under conditions similar to those described above for 
forming the film. 
Optionally, once the final product has been molded, water may be further 
removed by vacuum or otherwise to enhance the physical properties of the 
product, such as, for example to increase the stiffness of the product. 
PVA-containing products prepared in accordance with this invention exhibit 
good strength, (typically having a strength between 15,000 and 40,000 psi) 
and rigidity (typically having a Young's modulus between 50,000 and 
150,000 psi). 
The following specific example is furnished in order to illustrate the 
invention. It constitutes exemplification only and is not to be regarded 
as a limitation.

EXAMPLE 
A PVA/water mixture was prepared by placing 15 grams of 78,000 molecular 
weight PVA in a clean glass beaker and adding 7 grams of water heated to 
45.degree. C. in small increments while stirring vigorously. Vigorous 
stirring was continued for one minute after all the water had been added 
to ensure homogeneity of the mixture. The PVA/water mixture was kneaded 
into a small ball and placed in a vacuum chamber (0 to 25 mm Hg) at 
ambient temperature for about 2.5 hours. 
The ball of resin was then placed into a vacuum press to form a PVA film. 
The chamber of the vacuum press was evacuated to 0 to 30 mm Hg and the 
heater was set to 175.degree. C. After about six minutes, 1000 pounds of 
force was applied to the resin. When the temperature in the chamber 
reached 170.degree. C., 30,000 pounds of force was applied to the resin. 
This condition (170.degree. C., 30,000 lbs.) was maintained for five 
minutes. The press was cooled down while maintaining 30,000 pounds of 
force on the resin. Cool down included a water mist spray for six minutes 
followed by water for five additional minutes. The resulting PVA film 
removed from the press had a fairly uniform thickness of about 0.02 to 
0.04 inches. 
The film was then placed into a vacuum oven set at 60.degree. C. and 0 to 
25 mm Hg. After about eighteen hours in the vacuum oven, the film was 
removed and cut into strips approximately one-eighth of an inch in width. 
One strip was placed in each half of a suitable mold. The mold was closed 
and the loaded mold was placed into the vacuum press. The vacuum press was 
operated in the same manner described above to produce the PVA film. After 
cooling the molded PVA stent was removed and deflashed. 
The resulting stents were two inches in length and 0.017 inches in diameter 
and suitable for insertion into the vas deferens in order to hold these 
tubular structures in close apposition during repair of the structures 
such as by suturing or application of laser energy. The stents should 
maintain their integrity for at least ten minutes and preferably will 
dissolve, disintegrate, lose strength and/or flow away in the system 
within three hours, advantageously holding the tubular structures in 
position for a sufficient time to allow repair, such as by suturing or 
laser welding. It should be understood that stents of other dimensions can 
be produced in accordance with the present invention for use with or 
insertion into other body tissue, Five samples prepared as described above 
were subjected to a three point bending test regime based on ASTM D790. 
The test span length was 0.336 inches and the crosshead speed was set at 
0.5 inches per minute. The results are provided in Table I. 
TABLE I 
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Young's 
Sample # 
Max. Load (lbs.) 
Max. Stress (psi) 
Modulus (psi) 
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1 0.120 17,561 58,860 
2 0.215 37,443 140,192 
3 0.145 25,252 74,693 
4 0.125 20,656 65,350 
5 0.100 17,415 57,827 
Average 0.141 23,665 79,384 
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Objects formed in accordance with this invention may consist essentially of 
PVA. Alternatively, other components may be added to provide a desired 
characteristic or function to the object. For example, plasticizers such 
as glycerol or polyethylene glycols may be added to make polyvinyl alcohol 
thermoplastic. 
In addition, a coating of many types may be applied to the PVA object 
formed in accordance with this invention to alter the characteristics 
thereof. For example, a coating of a more slowly solubilized polymer may 
be applied to the PVA object to increase its resistance to hydrolytic 
attack. Suitable materials for a bioabsorbable coating include but are not 
limited to presently known synthetic or natural polymers which break down 
to non-toxic components when placed within a mammalian body, such as those 
identified in U.S. Pat. Nos. 4,719,917 and 4,916,193, which are 
incorporated herein by reference. For example, these include 
polyglycolide, polylactide, copolymers of glycolide and lactide, 
glycolide-trimethylene carbonate copolymer, mixtures of 
poly(glycolide-co-lactide) and polyethylene oxide, polydioxanone, 
polyesters formed from diols and succinic or oxalic acids, isomorphic 
copolyoxalates, poly(alkylene oxalates, polymalic acid, poly-beta-hydroxy 
acids, poly(hydroxyvalerates), poly(hydroxybuterates), polymers made from 
unsymmetrically-substituted 1,4-dioxane-2,5-diones, polycapralactone, 
copolymers of lactide or glycolide and epsilon cyprolactone, 
polyesteramides, partially oxidized cellulose surgical hemostats, chitin, 
chitin derivatives, collagen, regenerated collagen, catgut suture 
material, and mono-, di-, tri- and poly(saccharides). Preferred coating 
materials include polyglycolide, polylactide, copolymers of glycolide and 
lactide, and mixtures of polyglycolide-co-lactide and polyethylene oxide. 
It should, of course be understood that the PVA may be molded into any 
desired shape. Typical objects which may be formed from PVA in accordance 
with the present invention for medical use include, but are not limited to 
Orthopedic pins, clamps, screws and plates, clips, staples, bone 
substitutes, stents, needles and vascular implants.