CA2170037C

CA2170037C - Dehydration of hydrogels

Info

Publication number: CA2170037C
Application number: CA002170037A
Authority: CA
Inventors: Qi-Bin Bao
Original assignee: Stryker Technologies Corp
Current assignee: Howmedica Osteonics Corp
Priority date: 1993-09-16
Filing date: 1994-07-18
Publication date: 2000-05-30
Anticipated expiration: 2014-07-18
Also published as: US5522898A; EP0719117A1; ATE162385T1; DE69408153D1; EP0719117B1; WO1995007668A1; CA2170037A1; JPH08509891A; DE9490462U1; JP2935572B2; DE69408153T2

Abstract

Novel prosthetic nuclear implants for insertion into vertebral discs are prepared by dehydrating hydrated bulky hydrogel discs under specific conditions so as to reduce the water content as low as possible (down to about 10 % by weight) but without distortion of the implants, without the formation of concavities and sharp edges, and without changing the shape of the hydrated implant.

Description

Field of the Invention This invention relates to bulky hydrogels and relates in particular to a method of preparation of prosthetic nuclei for vertebral discs.
Backsround of the Invention An important area of research in the field of medical devices is the development of a prosthetic nucleus for a vertebral disc. In U.S. Patent 5,047,055, a prosthetic nucleus for implanting in the disc space after the removal of a degenerated or damaged nucleus of an intervertebral disc is disclosed and claimed, as well as a method for forming the prosthetic nucleus.
In making such a prosthetic nucleus for insertion, the implants made of bulky hydrogels should be dehydrated so that they have a water content as low as possible.
This allows for easy insertion of the disc component during surgery due to the accompanying reduction in volume. Additionally, it is desirable for the implant to have no distortions (i.e., no concavities or dimplings formed therein) and it is desirable that the apparent volume (defined herein to be the volume that the disc would have if it had no concavities and is equal to the largest cross-section of the disc multiplied by the largest disc width) of the implant be a minimum. Furthermore, it is desirable that the implant have no sharp edges. It is especially important to have a minimum dehydrated volume for an implant which is to be inserted percutaneously.
However, it has been found that when the bulky hydrogels as disclosed in U.S.
5,047,055 are dehydrated so as to reduce the water content as low as possible, under certain conditions, gross distortions of the implants occur. These distortions may not be acceptable in the intended medical application. For example, sharp edges on the superior and inferior surfaces of the implants can cause damage on the end-plates of the natural disc.
It is an object of this invention to produce vertebral disc implants which have a water content as low as possible, which exhibit (to the naked eye) no visible distortion of the implants and no sharp edges, and which have a minimum apparent volume.
Another object of this invention is a method of dehydration of a bulky hydrogel implant so as to maintain the original shape of the hydrated implant.
Yet another object of this invention is an implant having a water content which is as low as possible (i.e., below about 10~) and which has a minimal apparent 2170~37 volume, no sharp edges, and no visible distortion (that is, no visible concavities) in the implant.
Yet another object of this invention is to dehydrate vertebral disc implants to a consistent geometry and size.
Summary of the Invention These and other objects of the invention are satisfied by the method of the invention for dehydration of bulky hydrogel nuclear vertebral implants which are of a size weighing between about 3 and about 10 grams and of a shape which is substantially in the shape of a kidney (that is, a shape similar to that of a human vertebral disc nucleus) comprising dehydrating these implants under controlled conditions of relative humidity and temperature and time such that when the water content of these implants is within a critical range of about 30 to about 60°~ by weight, the samples dry so that they avoid the formation of any cavities. Above a water content of about 60 weight percent and below about 30 weight percent water content, the dehydration appears to be not so critical and the dehydration can proceed without distortions, under ambient conditions. Unexpectedly, it has been found that for these implants of the specific size (most preferably about 5 grams), kidney shape, and specific materials (bulky hydrogels as set out fully in U.S. Patent 5,047,055 and described below), the conditions for drying are critical for the water content range of about 30-60°~ and should be (a) relative humidity of at least about 80%, preferably in the range from about 90 to about 99°~, and most preferably at least 95°~, (b) a drying temperature within the range from about 10° to about 40°C and preferably about room temperature to about 35°C, and (c) a time of drying sufficient to enable the samples to be dried without distortion to a water content below about 30°r6 and preferably to about 10°~6, the time being generally several days.
Such implants when dehydrated according to the method of the invention exhibit an apparent volume which is a minimum, no sharp edges, and no visible distortions (i.e., no concavity) in the implant. When the conditions used in the method of the invention are not used for dehydrating the implants in the critical range, the resultant implants have visible distortions, have sharp edges, and do not have an apparent volume which is minimal.
Also according to the invention, a bulky hydrogel implant suitable for implantation as an artificial nucleus in a vertebral disc has a water content less than about 30 weight percent, has no visible distortions, has no sharp edges, has a dehydrated weight within the range from about 0.5 g, to about 3.0 g. and has a shape which is substantially in the shape of a kidney.
Description of the Preferred Embodiments Description of the Drawings Figure 1 is a set of three graphs of water content (in percentage of water by weight) plotted versus time of dehydration (in days) of three samples of hydrogels (further described herein and in U.S. Patent 5,047,055 .
Graphs A and B are for controls and Graph C is for an implant of the invention dehydrated according to the method of the invention, using in this case a humidity chamber with a relative humidity of 9896 and a temperature of 35 ° C. Graphs 1A and 1 B are described in Example 1 and Graph 1 C is described in Example 2 (given below).
Figure 2 is a graph of water content versus time (in days) for an implant of the invention (dehydrated so that it has no distortions therein, no sharp edges, and a minimal apparent volume, formed as described in Example 3 by dehydrating the implant within a container which is alternately uncovered and then closed.
Fig. 3 is an enlarged drawing of a fully hydrated hydrogel vertebral nucleus implant of kidney shape before dehydration. The length AA is the width of the implant.
Fig. 4 is an enlarged drawing of a dehydrated vertebral nucleus implant. The implant was dehydrated under ambient conditions. The distortion concavity surfaces and sharp edges at the comers are visible. The length B is the width.
Fig. 5 is an enlarged drawing of a dehydrated vertebral nucleus implant of the invention which was dehydrated under the controlled conditions as described in Example 2. There is no visible distortion, concavity, or sharp edges. The length A is the width. The apparent volume of the implant in Fig. 5 is smaller than that in Fig. 4, and width B is larger than width A.
Figures 3, 4 and 5 are drawn to the same scale.
The particular materials which are used for the synthetic vertebral nuclear disc implants are fully described and set out in U.S. Patent No. 5,047,055 , As set out in that patent, the preferred material of the implants is a hydrogel material, preferably highly hydrolyzed polyvinyl alcohol (PVA).
The amount of hydrolization may be between about 95 and 10096, depending on the WO 95/07668 PCT/IB9:t100220 preferred final water content desired, which is about 70 to about 90 weight percent.
Generally the final hydrogel water content increases as the percent of hydrolization of the initial PVA decreases.
The method of preparing the prosthetic nucleus implants is fully set forth in U.S.
Patent 5,047,055. Also as disclosed in that patent, other hydrogels (besides preferred PVA) which can be used in the synthetic nucleus implants include other hydrogels such as lightly cross-linked polymers of 2-hydroxyethyl methacrylate, or copolymers and terpolymers made from the combination of the monomers of an N-vinyl monomer, (for example, N-vinyl-2-pyrrolidone(N-VP)), a hydroxy alkyl methacrylate ester (for example, 2-hydroxyethyl methacrylate (HEMA)), an alkyl methacrylate (for example, methyl methacrylate (MMA), an ethylenically unsaturated acid (for example, methacrylic acid (MA)) and an ethylenically unsaturated base (for example N,N-diethylamino ethyl methacrylate (DEAEMA)) may be used. In general, any hydrogel that can be used for soft contact lenses can be used for the synthetic nucleus implants as long as the hydrogel exhibits a compressive strength of at least 4MNm-2.
The size of the implants will generally be within the range of from about 3 to about 10 grams before dehydration, and preferably will be about 5 grams before dehydration.
The shape of the synthetic nuclear disc implants will be substantially in the shape of a kidney or any shape similar to the shape of a human vertebral disc nucleus.
The relative humidity suitable for use in the method of dehydrating the implants is a relative humidity in the atmosphere of at least 80°ro and preferably within the range from about 90 to 9996 and most preferably above 9896.
The temperature to be used in the dehydration method should be within the range from about 10 to about 40°C and preferably will be within the range from about 20 to about 35 ° C. The higher the temperature, the faster the water within the hydrated implants will diffuse to the surface of the implants.
It has been found that for the bulky hydrogels used in the implants, for the size of the implants, and for the shape of the implants, it is very important (if not critical) that when the water content of the implants is between about 30 and about 60 weight percent, the implants should be dehydrated with the humidity being controlled within the ranges as described above, and at the temperatures as described above, and for a length of time which is quite long so as to avoid deformation of the implants when 2i?Q03'~

they are being dehydrated. When the relative humidity is lowered, the time of dehydration can also be lowered. However, to provide good results, the time of drying will generally be at least several days (i.e., more than two but fewer than many).
Examale 1 i(Control~
A hydrogel prosthetic nucleus implant starting with a wet weight about 5 grams and with a water content of about 8596 was dehydrated under conditions of ambient temperature and humidity. Although the laboratory has air conditioning, the relative humidity was in the range of about 4596 to about 8596 during the period of the dehydration. The relative humidity each day during the dehydration period was recorded, and the averages are labeled in the plot. The room temperature was relatively stable (between 20-22°C). The high relative humidity (above 75°.6) in the first two days made this dehydration very slow during this period. The weight of the implant was monitored over the dehydration period, and the water content of the implant vs.
the time is plotted in Figure 1 (curve A). The shape of the implant was also monitored visually over time. In the early dehydration period when the implant still had high water content (wherein the water content was between about 8596 to about 6596), the implant maintained its original shape without distortion even though the water content (and thus the weight) of the implant decreased relatively quickly. In this range of water content, the implant remained very soft to the touch. As dehydration continued, the implant surfaces started to become rigid; and concavities became visible on the surfaces when the implant had a water content of about 50°~6. The concavities increased as the water content decreased further.
In Figure 1, curve B is the dehydration of a substantially similar implant dehydrated with low relative humidity (about 6096) in the same laboratory.
Again, concavities formed.
EXAMPLE 2 (Invention) A similar size hydrogel nucleus implant as was used as starting material in Example 1 was dehydrated in a Temperature/ Humidity controlled chamber, called a TH
Jr. (and manufactured by Tenny Engineering, Inc., Union, NJ) at 35°C
and at a relative humidity of 9896. The weight and the shape of the implant were checked over time.
' Water content vs. time is plotted in Figure 1, curve C. It can be seen that the dehydration rate was substantially decreased at high humidity, as compared with the rate of low humidity. The implant kept its original shape without the formation of any visible concavities even when the water content dropped to about 2596.
Next, the implant was dried further in a vacuum oven at 35°C. This further dehydration did not result in any visible concavity formation (as viewed by the naked .
eye).
EXAMPLE 3 (Invention) In this example, a hydrogel implant as was used as starting material in Example 1 but with a water content of about 7796 was first allowed to dehydrate quickly in air until the water content was about 5496. This occurred over about one day, and the relative humidity of the air was between 20-40°~6. Then, the implant was kept in a small closed container for the next three days. Then the implant was exposed to air again (with a relative humidity of 20-4096 for a period of about one day) and more water evaporated. Next, the hydrogel implant was placed in the container again.
These steps were repeated until the water content of the implant was about 3096.
Then the implant was allowed to dehydrate further under vacuum. (This further dehydration could have been done alternatively in air but for a longer period of time.) The implant dehydrated in this way provided a dehydrated implant (with water content of less than 10 weight 96) with no concavity on the surfaces.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method of dehydrating a bulky hydrogel nuclear vertebral implant weighing before dehydration in the range between 3 and 10 grams, having a shape substantially in the shape of a kidney and having a water content within the range from 30 to 90% by weight, which method comprises:
dehydrating the implant, wherein when the implant has a water content of between 30 and 60% by weight, the implant is dehydrated at a relative humidity of at least about 80% at a drying temperature within the range from 10 to 40°C and for a time of drying which is more than 2 days and is sufficient to enable the implant to be dried without distortion to a water content below 30%.

2. The method according to claim 1, wherein the implant is made of bulky hydrogel material selected from the group consisting of hydrogels that can be used for soft contact lenses provided that the hydrogel exhibits a compressive strength of at least 4 MNm-2, wherein the relative humidity is within the range from about 90 to about 99% and wherein the drying temperature is within the range from about 20 to about 35°C.

3. The method according to claim 2, wherein the relative humidity is at least about 95%.

4. The method according to any one of claims 1 to 3, wherein the dehydration takes place within a humidity chamber.

5. The method according to any one of claims 1 to 4, wherein the hydrogel is of polyvinyl alcohol having a degree of hydrolyzation of 95 to 100%.

6. The method according to any one of claims 1 to 5, in which the bulky hydrogel nuclear vertebral implant before the dehydration at the specified relative humidity and drying temperature has a water content within the range from 70 to 90%
by weight; and which further comprises a preliminary drying of the implant to reduce the water content to about 60% by weight prior to the dehydration step at the specified relative humidity and drying temperature.

7. The method according to claim 6, wherein the preliminary drying prior to the dehydration step is conducted at a relative humidity of 20 to 40%.

8. The method according to any one of claims 1 to 5, wherein the bulky hydrogel nuclear vertebral implant has a water content within the range from 70 to 90% and is subjected as it is to the dehydration at the specified relative humidity and drying temperature.

9. The method according to any one of claims 1 to 8, wherein the bulky hydrogel nuclear vertebral implant after the dehydration step at the specified relative humidity and drying temperature has a water content of 25% and is subjected to a further drying in a vacuum to reduce the water content to 10%.

10. A method of dehydrating a bulky hydrogel nuclear vertebral implant weighing before dehydration in the range between 3 and 10 grams, having a shape substantially in the shape of a kidney and having a water content within the range from 70 to 90% by weight, which method comprises:
a preliminary drying of the implant at a relative humidity less than 80% until the water content becomes about 60% by weight; and a further dehydration of the implant at a relative humidity of at least about 80% at a drying temperature within the range from 10 to 40°C and for a time of drying which is more than 2 days and is sufficient to enable the implant to be dried without distortion to a water content below 30%.

11. The method according to claim 10, wherein the relative humidity of the preliminary drying is 20 to 40%.

12. The method according to claim 10 or 11, wherein the further dehydration consists of a plurality of steps each conducted under the specified conditions with a step of exposure of the implant to air at a relative humidity of 20 to 40%
between the steps under the specified conditions so that the water content of the implant after the plurality of the steps becomes below 30%.

13. A method of dehydrating a bulky hydrogel nuclear vertebral implant weighing before dehydration in the range between 3 and 10 grams, having a shape substantially in the shape of a kidney and having a water content within the range from 70 to 90% by weight, which method comprises:
a dehydration of the implant at a relative humidity of at least about 80% at a drying temperature within the range from 10 to 40°C and for a time of drying which is more than 2 days and is sufficient to enable the implant to be dried without distortion to a water content below 30%.

14. The method according to any one of claims 10 to 13, which additionally comprises:
further drying the implant in a vacuum oven until the water content becomes about 10%.