JPS59137063A - Radiation resistant dialytic membrane - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention Radiation sterilization of dialysis membranes, such as the 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.

Toshi Co., Ltd.'s Special Publication in 1982 entitled "Method of Sterilizing Dialysis Machines"
No. 23,620 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. Therefore, dialysis fluids with such membranes cannot withstand winter weather in northern climates on loading docks or in 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 is possible to have a membrane treated according to the present invention with only a small degree of degradation.

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.

According to the present invention, a substantially anhydrous dispersion of 3 to 25 volume % of a liquid organic polyol having a molecular weight of 200 or less and 75 to 97 volume % of a volatile non-reactive solvent is added to the diffusion membrane. applies. 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, a more concentrated liquid organic polyol can be applied to the diffusion membrane as a more 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, with a subsequent solvent washing step, consists of 10 to 100% liquid organic polyol and a volatile non-reactive solvent O.
Compositions containing from 90% to 90% can be used in a substantially anhydrous state. For example, a bundle of hollow cellulosic dialysis fibers was prepared using 75% glycerin and 2% isopropanol.
The polyol can be applied by dipping in a solution consisting of 5% and then gently rinsing the fiber bundle in isopropanol to remove excess glycerin.

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 because 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 trichlorotrifluoromethane, such as 1°1.2- Trichlor-1,
It can be 2,2-trifluormethane. Mixtures of these with alcohols can likewise be used.

It is generally preferred to treat cellulosic dialysis membranes according to 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 according to the invention preferably comprises glycerin 4 to 10
% by volume, the remainder 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 manufactured by assembling hollow fiber bundles into a housing by techniques similar to those described in, for example, U.S. Pat. No. 4,227,295. After botting the ends and cleaning with solvent, they were removed from the production line. These hollow fiber materials contain about 2 to 3% by weight of glycerin as a plasticizer.

Before placing the end caps on the dialyzers, they were placed in an alcohol parts wash centrifuge.

A Barrett alcohol centrifuge manufactured by Pallet Centrif Negal, Inc., Massachusetts, may be used. The alcohol centrifuge is diluted with 5% glycerin by volume.
filled with isopropanol solution containing. The dialyzer was allowed to soak in this solution for 5 to 10 minutes. The solution was then drained from the dialyzer, the centrifuge was spun at approximately 40 Orpm, and the remaining solution was further drained from the dialysate boat. Rotation was stopped to allow liquid to drain from the boat and rotation was resumed at approximately 9-00 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.

The treated dialyzers exhibited significantly improved resistance to radiation damage during gamma sterilization when compared to equivalent dialyzers manufactured on the same production line without the treatment of the present invention.

Specifically, three dialyzers treated as described above and two untreated control dialyzers from the same production process were gamma sterilized at doses ranging from 2.3 to 2.66 Megaland (Ill. by Isomedix, Inc., Morton Grove, State).

The three dialyzers treated as above were 200mmHH
at a pressure of 3.3, 3.2 and 3,1, respectively.
m! The membrane exhibited an ultrafiltration coefficient of Q/hr, /mug, and showed greatly improved membrane ultrafiltration performance after gamma sterilization.

Patent Applicant: Baxter, Travenol, Laboratories, Inc. Vol.
・i, ji:,',ll' 1 358-

Claims (1)

[Scope of Claims] (1) A substantially anhydrous dispersion of 3 to 25 volume % of an organic polyol having a molecular weight of 200 or less and 75 to 97 volume % of a volatile non-reactive solvent is passed through the dialysis membrane, and then A method for making a dialysis membrane resistant to radiation damage, comprising draining the dispersion from the diffusion membrane. (2) The method of item 1, wherein the organic polyol is glycerin. (3) The first volatile non-reactive solvent is alcohol.
Section method. (4) The method of item 1, wherein the volatile non-reactive solvent is isopropanol. (5) The method of item 1, 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. (6) the dialysis membrane is in the form of hollow cellulosic capillary fibers held in a bundle within a tubular housing, and the fibers and housing are dipped into the dispersion to apply the dispersion to the dialysis membrane; Method of Section 1. (7) The method of claim 1, wherein the dispersion contains 4 to 10% by volume glycerin, the remainder being a volatile non-reactive solvent. (8) The method of item 7, wherein the volatile non-reactive solvent is isopropanol. (9) A substantially anhydrous dispersion of 4 to 10% by volume glycerin and 90 to 96% volatile non-reactive solvent to a dialysis membrane in the form of hollow cellulosic capillary fibers held as a bundle within a tubular housing. immersing the dialysis membrane into the dispersion in a manner that allows the dispersion to come into intimate contact with the inside and outside of the hollow cellulosic capillary fibers; A method for making a dialysis membrane resistant to radiation damage, characterized in that the dispersion liquid is drained while the dialysis membrane is being drained. 00) The volatile non-reactive solvent is alcohol No. 9
Section method. 01) The method of clause 9, wherein the volatile non-reactive solvent is isopropanol. a2) applying to the dialysis membrane a substantially anhydrous composition of 10 to 100% by volume of an organic polyol having a molecular weight of 200 or less and O to 90% by volume of a volatile non-reactive solvent;
A method of making a dialysis membrane resistant to radiation damage, characterized in that the dialysis membrane is subsequently washed so as to remove some, but not all, of the applied organic polyol. (odor) The method of paragraph 12, wherein the organic polyol is glycerin. (2) The method of paragraph 12, wherein the volatile non-reactive solvent is isopropanol. ω) The dialysis membrane is bundled in a tubular housing. 13. The method of claim 12, wherein the fiber is in the form of a retained hollow cellulosic capillary fiber, and the fiber and housing are immersed into the dispersion for application of the dispersion to a dialysis membrane. (g) The method of item 12, wherein the dialysis membrane is washed with isopropanol after applying the mixture.