Chemical apparatus and process disinfecting – deodorizing – preser – Process disinfecting – preserving – deodorizing – or sterilizing
Reexamination Certificate
1998-07-31
2001-04-10
Thornton, Krisanne (Department: 1744)
Chemical apparatus and process disinfecting, deodorizing, preser
Process disinfecting, preserving, deodorizing, or sterilizing
C210S321610, C210S321710, C422S022000, C422S028000, C422S044000, C422S045000, C428S423100, C528S048000
Reexamination Certificate
active
06214290
ABSTRACT:
FIELD OF THE INVENTION
The subject-matter of the invention is medical items based on polyurethane-generating compositions which are non-cytotoxic after sterilization or disinfection by an oxidizing process and more particularly potting bodies for flat-membrane or hollow-fiber medical exchangers. Another subject-matter of the invention is a process for the preparation of these polyurethane medical items which makes it possible to greatly limit the cytotoxicity resulting from the sterilization or from the disinfection by an oxidizing process, such as ionizing radiation (gamma radiation, electron beam), gaseous peroxides (so-called cold plasma sterilization), liquid peroxides or any other physical or chemical process involving an oxidation reaction capable of denaturing the sterilized material.
Depending on the situation, the polyurethane potting bodies are intended to form:
a cylindrical partition for separating the two compartments of a medical exchanger, the membrane of which is composed of a bundle of hollow fibers. The operation which consists in producing such a separating partition is usually denoted under the term “potting”;
or a leaktight seal in a medical exchanger comprising a semi-permeable flat membrane. The operation which consists in producing such a seal is usually denoted under the term “leaktightness packing”. Nevertheless, in order to simplify the present description, this operation will also be denoted under the term “potting”.
Out of concern for clarity of the present description, the term “seal” will be used to denote without distinction a leaktight seal in semi-permeable flat-membrane medical exchangers or a cylindrical separating partition in medical exchangers in which the membrane is composed of a bundle of semi-permeable hollow fibers.
The present invention is in particular of use in the manufacture of exchangers for medical applications in the form, for example, of dialysers, haemofilters and oxygenators.
BACKGROUND OF THE INVENTION
It is common practice to manufacture exchangers for medical applications by following the general stages which follow:
preparing a semi-permeable membrane from a flat membrane or conforming a bundle of semi-permeable hollow fibers from hollow fibers;
mounting the semi-permeable membrane or else the bundle of hollow fibers in a casing and forming, depending on the situation, a leaktight seal or a cylindrical partition for separating the two compartments, using a polyurethane-generating adhesive composition;
if appropriate, attaching end fittings to the casing and
sterilizing the medical device obtained.
The polyurethane-generating adhesive compositions used to prepare a seal in a medical exchanger generally comprise, before polymerization, one or more polyiso-cyanates, one or more polyols and, optionally, one or more polyfunctional crosslinking agents and/or one or more catalysts.
The polyurethane, once it is cured, has the essential function of forming a leaktight seal, in order for there to be no infiltration between the two compartments of the exchangers or with the outside. The risk of infiltration must in particular be avoided between the blood compartment and the dialysate compartment of medical exchangers for blood treatment. To achieve this, the polyurethane adhesive composition must exhibit satisfactory adhesion with the semi-permeable membranes of the exchangers, whatever the chemical nature of the materials of which they are composed. This composition must also exhibit satisfactory adhesion with the components of the exchangers with which it is brought into contact, such as the casing.
Another important quality required of exchangers for biomedical use is the biocompatibility of cured and sterilized polyurethane potting bodies, more especially their non-cytotoxicity. Otherwise, the stage of sterilization or of disinfection by an oxidizing process, in particular when it is a sterilization by irradiation, can render polyurethane cytotoxic.
Previously, in order to form non-cytotoxic potting bodies, various solutions were provided, thus:
in U.S. Pat. No. 4,332,927, provision was made for polyurethane-generating compositions comprising at least one prepolymer with isocyanato endings (—NCO), at least one polyol and a catalytic amount of a dicarboxylated dialkyltin compound;
in European Patents No. 0,393,545 and No. 0,413,265 and U.S. Pat. No. 5,306,798, various polyurethane-generating adhesive compositions based on diphenylmethane diisocyanates (MDI) or on MDI derivative, and on specific polyols, were provided.
SUMMARY OF THE INVENTION
It has now been found, differently and surprisingly, that it is possible to manufacture polyurethane medical articles sterilized or disinfected by an oxidizing process which are non-cytotoxic, in particular polyurethane potting bodies, which are, in addition, sufficiently adhesive to semi-permeable membranes of exchangers but non-cytotoxic after sterilization or disinfection by an oxidizing process. In accordance with the invention, the starting point is a polyurethane-generating composition comprising:
at least one polyisocyanate, preferably a non-aromatic polyisocyanate, in the monomer or prepolymer state;
at least one polyol in the monomer or prepolymer state; and
at least one dialkyl sulphoxide compound, preferably in the proportion of at least 2% by weight of the total weight of the polyol or polyols.
(Dialkyl sulfoxide is mentioned in a completely different context as an anti-slag additive to urethane-base materials in U.S. Pat. No. 4,123,412.)
Advantageously, the polyurethane-generating composition additionally comprises at least one catalyst of the polymerization reaction of a polyisocyanate and of a polyol.
Another subject-matter of the present invention is a process which makes it possible to reduce the cytotoxicity of polyurethane medical items, in particular polyurethane potting bodies, liable to appear after sterilization or disinfection by an oxidizing process, characterized in that the polyurethane-generating composition is prepared from:
at least one polyisocyanate, preferably a non-aromatic polyisocyanate, in the monomer or prepolymer state;
at least one polyol;
at least one dialkyl sulphoxide compound, the amount of dialkyl sulphoxide compound preferably being at least equal to 2% by weight with respect to the total weight of the polyols; and
if appropriate, at least one catalyst of the polymerization reaction of a polyisocyanate and of a polyol.
Still another aspect of the invention can be characterized as an improved article of manufacture comprising a potting compound in contact with a flat membrane or hollow fiber medical exchanger, wherein the improvement comprises the nature of the potting compound as described herein.
In the context of the present invention, the term non-cytotoxic polyurethane medical items is understood to mean items resulting in a percentage of inhibition of cell growth (% ICG) which is greatly reduced by virtue of the presence of at least one dialkyl sulphoxide compound. This percentage of ICG is preferably at most equal to 30% on average over at least 3 samples, when the polyurethane medical items are subjected to the biological tests of medical and dental equipment and devices, part 5: in vitro methods, of the ISO Standard 10-993, supplemented by the conditions for measurement of cytotoxicity used by the assignee company. These specific conditions for measurement of cytotoxicity are set out hereinbelow, with the examples.
An essential characteristic of the invention lies in the use of at least one dialkyl sulphoxide compound for preparing non-cytotoxic polyurethane medical items, more especially potting bodies intended for coating medical exchangers in the form of flat membranes or hollow fibers.
The alkyl radicals of the dialkyl sulphoxide compounds suitable for the invention can comprise one or more functional groups such as hydroxyl groups but are devoid of functional groups which react sharply with an isocyanato group, such as amine groups or thiol groups.
The dialkyl sulphoxide compounds suitable for the invention have a melting point a
Hospal Industrie
Millen White Zelano & Branigan P.C.
Thornton Krisanne
LandOfFree
Non-cytotoxic polyurethane medical items does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Non-cytotoxic polyurethane medical items, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Non-cytotoxic polyurethane medical items will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2480063