Chemistry: molecular biology and microbiology – Maintaining blood or sperm in a physiologically active state...
Reexamination Certificate
2000-09-29
2004-10-05
Marx, Irene (Department: 1651)
Chemistry: molecular biology and microbiology
Maintaining blood or sperm in a physiologically active state...
C435S238000
Reexamination Certificate
active
06800432
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates generally to apparatus and methods for inactivating viral contaminants that may be present in the body fluids. More specifically, the invention relates to apparatus and methods for photodynamically inactivating viral contaminants in body fluids.
In a variety of therapies, such as transfusions and transplants, body fluids, especially blood components such as red blood cells, platelets, plasma, leukocytes, and bone marrow, are collected from one or more individuals and then infused into a patient. Although such therapies provide treatments, some of which are life saving, due to the transmission of infectious diseases there may be potential risks involved with such therapies.
By way of example, it is known that blood can carry infectious agents such as hepatitis virus, human immunodeficiency virus (an etiological agent for AIDS), and cytomegalovirus. Although screening methods exist to identify blood that may include such viruses, blood containing viruses, and other disease causing pathogens, such as bacteria, cannot be 100% eliminated from the pool of possible blood component supplies. Therefore, there is still a small risk that blood transfusions can transmit viral or other infections.
Accordingly, a goal of recent biomedical research has been to reduce the risk of transmitting an infectious agent by selectively inactivating or depleting pathogens present in such blood components. One approach has been to utilize photosensitive (photoactive) agents that when activated by light of the appropriate wavelength will destroy the ability of the pathogen to cause infection. The use of photodynamic therapy has been suggested as a way to eradicate infectious agents from collected blood and its components prior to storage and/or transfusion.
A number of different photoactive agents have been proposed as possibilities to be used to eradicate viral and other contaminants in body fluids. Such photoactive agents include: psoralens; porphyrins; phthalocyanines; and dyes such as methylene blue. See, for example, U.S. Pat. Nos. 4,748,120; 4,878,891; 5,120,649; and German Patent Application No. DE 39 30 510 A1 (Mohr).
Although much effort has been focussed on commercializing such methods using photoactive agents, the inventors believe that such methods are currently not commercially viable. Even though an ideal system for utilizing a photoactive agent to treat blood to eradicate or remove viral and other contaminants has not been developed, it is envisioned that such a system would entail combining the blood with the photoactive agent in a container and irradiating the resultant mixture with light of the appropriate wavelength.
It is known, of course, to use blood pack units to collect blood. The blood pack units include a container typically constructed from a plastic material, usually a polyvinyl chloride material. The blood pack units are connected to tubes that allow blood to be infused into the container as well as to be accessed therefrom.
Of course, blood pack units must be sterilized. Typically, sterilization takes place by steam sterilization at a temperature of above 100° C. for a predetermined period of time.
One photoactive agent that appears to be promising with respect to eradicating viruses and bacteria from blood is methylene blue. Methylene blue 3-7-bis(dimethylamino)phenothiazine-5-ium chloride (C
16
H
18
ClN
3
S), in the presence of light has been reported to damage DNA and generate singlet oxygen which damages the virus envelop. Accordingly, it can be used to selectively, in a controlled manner, modify the DNA and RNA of bacterial and viral contaminants thereby inactivating the pathogens. See U.S. Pat. No. 4,950,665.
It has recently been determined, however, that if methylene blue is placed into a standard blood pack unit constructed from PVC under standard conditions and the unit is then heat sterilized, that at least a certain amount of the methylene blue migrates into the PVC layer reducing the methylene blue present. The specific amount of methylene blue that migrates is variable depending upon the conditions. However, envisioned methods of using methylene blue to treat blood and other body fluids require that precise amounts of methylene blue be used.
This unfortunately requires that the blood packs must be sterilized prior to methylene blue being added thereto. This can create logistic problems as well as increase the cost of creating the product. Likewise, during the methylene blue filling process, there is the risk of contaminating the sterilized container.
However, it has recently been discovered that methylene blue can be housed in certain containers, or under certain conditions, and sterilized with the blood pack unit without the methylene blue migrating into the plastic. It has been found that two of the parameters that have a great effect on preventing methylene blue from migrating into the plastic are: the type of plastic; and the pH of the methylene blue solution.
It has been found that methylene blue does not migrate into non-PVC material as well as into PVC material under sterilization conditions. One or more suitable containers providing a steam sterilizable housing for the methylene blue are disclosed in U.S. Pat. No. 6,207,107, filed Sep. 28, 1992, the disclosure of which is fully incorporated herein by reference. The housing includes at least an inner surface, the surface that contacts the methylene blue solution, that is constructed from a non-PVC material.
SUMMARY OF THE INVENTION
The present invention provides a method and apparatus for inactivating viral contaminants in a body fluid. By mixing both methylene blue and the body fluid within a container, and then subjecting the container to a suitable light field under no-flow conditions, viral contaminants can be inactivated.
To this end, in an embodiment the invention provides a method for inactivating viruses in a body fluid, comprising the steps of forming a mixture including a therapeutically effective amount of methylene blue and an amount of a body fluid in a container under sterile conditions, and irradiating the mixture with a light field of a suitable intensity and wavelength for activating the methylene blue for a time sufficient to inactivate viruses in a mixture. During the process, the mixture is maintained in a substantially static state within the container.
In an embodiment of the invention, the body fluid a blood component.
In an embodiment of the invention, the blood component is selected from the group consisting of: plasma, red blood cells, white blood cells, leukocytes, bone marrow, and platelets.
In an embodiment of an invention, the step of forming a mixture comprises the step of adding the methylene blue to a container in which the body fluid is already stored.
In an embodiment of the invention, the step of irradiating includes the step of transporting the mixture in the container along a path of a light field.
In an embodiment, the invention provides the further step of allowing excess methylene blue to leach out into the container after the irradiation step.
In an embodiment of the invention, the light field is generated by an array of light emitting diodes.
In an embodiment, the invention provides an apparatus for inactivating at least viruses in a body fluid with methylene blue. The apparatus comprises at least one light source disposed along a path of travel and configured to generate a light field on the path of travel with a frequency suitable for activating methylene blue while not adversely effecting body fluids. The apparatus also includes a transport associated with the light source and configured to transport a container enclosing a mixture of the body fluid and a therapeutically effective amount of the methylene blue along the path of travel and within the light field generated by the light source.
In an embodiment of the invention, the light source comprises a light emitting diode.
In an embodiment of the invention, the light emitting diode light source generates a light field with a wavelength of about 670 n
Bratten William
Foley John
Wolf, Jr. Ludwig
Baxter International Inc.
Bell Boyd & Lloyd
Kowalik F. C.
Marx Irene
Mayo M. C.
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