JPH0432665B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field Radiation sterilization of dialysis membranes, such as cellulosic hollow fibers, used commercially in hemodialyzers today is advantageous. Although the majority of commercially available cellulose-based dialyzers are sterilized with ethylene oxide, radiation sterilization can eliminate undesirable trace components that may remain in otherwise sterilized dialysers.

Toray Industries, Inc.'s Special Publication No. 55-23620 titled Method for Sterilizing Dialysis Equipment describes moistening the dialysis membrane with water or an aqueous solution of a non-toxic water-soluble substance such as common salt or glycerin. .
This treatment is claimed to reduce radiation damage when radiation sterilizing dialysis membranes.

However, as a disadvantage, wet dialysis membranes present substantial drawbacks during shipping and storage. In particular, wet membranes cannot tolerate freezing or are damaged by the formation of ice crystals. For this reason, dialysis fluids with such membranes cannot withstand the winter months of northern climates in loading docks or unheated trucks without risking destruction of the dialysis membrane by freezing. For this reason, they must be handled with special handling and transported in heated trains or trucks in northern regions during the winter.

According to the present invention, dialysis and other diffusion devices are made resistant to radiation sterilization, i.e., the performance parameters of the membrane, expressed in terms of dialysis performance, are much more resistant to gamma sterilization than dry gamma sterilized membranes. It can be processed to avoid a slight decrease.

Some forms of cellulose-based dialysis membranes commonly used commercially in dialyzers contain glycerin as a plasticizer. Nevertheless, such membranes tend to lose their properties to a greater extent during gamma sterilization than equivalent membranes treated according to the present invention.

DESCRIPTION OF THE INVENTION According to the invention, a substantially anhydrous dispersion of 3 to 25% by volume of a liquid organic polyol with a molecular weight of less than 200 and 75 to 97% by volume of a volatile non-reactive solvent is applied to a diffusion membrane. . The dispersion is then drained from the dialysis membrane. As a result, the dialysis membrane becomes resistant to radiation damage.

Without wishing to be bound by any particular theory of operation of the present invention, and indeed the details of its operation are not fully understood, it is believed that the organic polyol applied to its exposed surface allows the membrane to absorb gamma rays. appears to be protected from the degrading effects of radiation experienced during sterilization operations such as

Alternatively, the highly concentrated liquid organic polyol can be applied to the diffusion membrane as a highly concentrated polyol solution in a volatile non-reactive solvent. Typically, in this case the polyol is present in excess, removing some of the polyol from the vicinity of the membrane while leaving the deposited or absorbed polyol on the membrane in an excessively non-viscous concentration, and resistant to radiation damage. A post-cleaning step is required to ensure this. In particular, this application step, followed by a solvent wash step, allows compositions containing 10 to 75% liquid organic polyol and 25 to 90% volatile non-reactive solvent to be used in a substantially anhydrous state. . For example, the polyol can be removed by soaking a bundle of hollow cellulosic dialysis fibers in a solution consisting of 75% glycerin and 25% isopropanol and then gently washing the fiber bundle in isopropanol to remove excess glycerin. Can be applied.

The term "substantially anhydrous" as used above is not intended to exclude absorbed water or other trace amounts in the organic polyol and volatile non-reactive solvent. However, it is considered undesirable to add large amounts of water to the dispersion, as such water, if frozen, will form ice crystals that will rupture the membrane.

Generally, it is desirable that the liquid organic polyol be glycerin because glycerin is non-toxic and metabolizable so that small amounts of glycerin can be safely injected into the patient during dialyzer use.

The volatile non-reactive solvent may preferably be an alcohol having up to 3 carbon atoms, such as methanol, ethanol, n-propanol and isopropanol. Generally, isopropanol is preferred due to the well-known toxicity of methanol and the legal and administrative issues involved in using ethanol on a commercial basis.

Alternatively, the volatile non-reactive solvent may be a volatile non-reactive chlorofluorocarbon, such as one of the solvents sold under the trademark Freon by DuPont, particularly trichlorotrifluoroethane, such as 1,1,2- It can be trichloro-1,2,2-trifluorethane. Mixtures of these with alcohols can likewise be used.

It is generally preferred to treat cellulosic dialysis membranes in accordance with the present invention. However, the present invention is not intended to be limited to the treatment of cellulosic dialysis membranes, but can be used with other types of membranes as well. Preferably both sides of the membrane are treated, but only one side may be treated if desired.

The dispersion of the invention preferably contains 4 to 10% by volume of glycerin, the balance being a volatile non-reactive solvent such as isopropanol. Bundles of hollow dialysis fibers treated with such dispersions undergo little or no perceptible change in appearance and feel.

The above description and the following examples are provided for the purpose of illustrating the invention and are not intended to limit its scope as defined in the claims.

Example 1 A commercially available hollow cellulosic fiber type dialyzer (Travenol CF1211 dialyzer) was assembled with hollow fiber bundles in a housing, e.g.
The ends were potted using a technique similar to that described in No. 4,227,295 and removed from the production line after solvent cleaning. These hollow fiber materials contain about 2 to 3% by weight of glycerin as a plasticizer.

Before placing the end caps on these dialyzers,
They were placed in an alcohol parts cleaning centrifuge. A Barrett alcohol centrifuge manufactured by Barrett Centrifugal, Inc. of Worcester, Massachusetts may be used. The alcohol centrifuge was filled with an isopropanol solution containing 5% by volume glycerin. The dialyzer was allowed to soak for 5 to 10 minutes while immersed in this solution. Then, drain the solution from the dialyzer and centrifuge approximately
Rotate at 400 rpm and further drain the remaining solution through the dialysate port. Rotation was stopped to allow liquid to flow out of the port, and rotation was resumed at approximately 900 rpm to help dry the remaining alcohol.

The dry dialyzer showed no visible signs of a glycerin film supported by the membrane, but the clear housing showed a slight oily indication.

When a treated dialyzer is compared to an equivalent dialyzer manufactured on the same production line without the treatment of the present invention,
It showed significantly improved resistance to radiation damage during gamma sterilization.

In particular, three dialyzers treated as described above,
Two untreated control dialysers from the same production run were gamma sterilized (by Isomedeix, Inc., Morton Grove, Ill.) at doses of 2.3 to 2.66 megarads.

The ultrafiltration coefficients of the two control dialyzers at a pressure of 200 mmHg were 2.3 and 2.5 ml/hr./, respectively.
mmHg, but the three dialyzers treated as described above were each tested at a pressure of 200 mmHg.
It exhibited ultrafiltration coefficients of 3.3, 3.2 and 3.1 ml/hr./mmHg, indicating greatly improved membrane ultrafiltration performance after gamma sterilization.

Claims (1)

[Claims] 1. A substantially anhydrous dispersion of 3 to 75 volume % of an organic polyol with a molecular weight of 200 or less and 25 to 97 volume % of a volatile non-reactive solvent is applied to a dialysis membrane, and then the dialysis membrane is Radiation-damaged dialysis membrane characterized by removing some, but not all, of the applied organic polyol by draining the dispersion from or washing the dialysis membrane with the volatile non-reactive solvent. A treatment method that makes it resistant to. 2 The dispersion liquid contains the organic polyol 3 to 25
% by volume, and the dispersion is drained from the dialysis membrane after application. 3 The dispersion liquid contains 10 to 10% of the organic polyol.
75% by volume, and the dialysis membrane is washed with the volatile non-reactive solvent after applying the dispersion. 4. The first organic polyol is glycerin.
3. The treatment method described in Section 2, Section 2, or Section 3. 5. The method of item 1, 2 or 3, wherein the volatile non-reactive solvent is an alcohol. 6. The treatment method according to item 5, wherein the alcohol is isopropanol. 7. The treatment method according to item 1, 2 or 3, wherein the volatile non-reactive solvent is a mixture of a volatile chlorofluorocarbon having 3 or less carbon atoms and an alcohol having 3 or less carbon atoms. 8. The dialysis membrane is in the form of hollow cellulosic capillary fibers held as a bundle in a tubular housing, and application of the dispersion is carried out by dipping the fibers and housing into the dispersion. The processing method described in item 1, item 2, or item 3.