Chemistry: molecular biology and microbiology – Differentiated tissue or organ other than blood – per se – or...
Reexamination Certificate
2001-04-23
2004-06-08
Saucier, Sandra (Department: 1651)
Chemistry: molecular biology and microbiology
Differentiated tissue or organ other than blood, per se, or...
C435S001200, C424S543000
Reexamination Certificate
active
06746836
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a novel use for a protein derived from keratin. In particular, it proposes the use of alpha-keratose as a blood plasma expander, for the preservation and transportation of organs and for the formed elements of blood.
2. Description of the Background Art
Heretofore, an intense research effort has been made and many materials have been developed that lend themselves for possible use as a blood plasma expander. A blood plasma expander is generally used for fluid replacement in the treatment of extensively burned individuals to remove burn toxins and/or prevent burn shock. Fluid replacement therapy may also be required by individuals with open wounds and extensive external and/or internal bleeding, immunologic defects, clotting problems, or severe diarrhea.
Blood plasma expanders have been made from materials consisting of crystalloid solutions or colloidal-like polymeric solutions. The crystalloid materials include saline, compositions of saline and glucose, Hartmann's solution, and Ringer's solution. The colloidal-like polymeric materials include pectin, gelatin, albumin, hydroxyethyl starch, polyvinyl pyrrolidone, dextran and cellulose derivatives.
Some blood plasma expanders have been made from blood and blood fractions. However, the use of blood and blood fractions is fraught with disadvantages. For example, the use of whole blood often is accompanied with the risk of transmission of hepatitis-producing viruses or other viruses which complicate the patient's recovery. Additionally, the use of whole blood requires blood-typing and cross-matching to avoid immunohematological problems and interdonor incompatibility.
Therefore, a blood fraction plasma, which is a physiologically balanced colloidal solution that fulfills many of the requirements of a blood volume expander, cannot be safely used for this purpose unless further efforts in time and expense are made to remove infectious agents. It would also be advantageous to remove isoagglutinins. Clearly it is desirable to use non-blood based blood substitutes. In view of the above presentation, it becomes immediately apparent that a need exists for a therapeutic product useful as a blood plasma expander without the above drawbacks.
Plasma and albumin, as blood plasma expanders, have disadvantages in their availability, initial expense, storage, and risk of viral infection. Whereas, dextrans of high molecular weight are especially useful in that they are not excreted as rapidly as low molecular weight dextrans, they present the dangers of rouleaux formation, sludging of erythrocytes, and possible anaphylaxis. Hence the compromise using dual high and low molecular weights of oncotic agents with differential clearance rates, such as dextrans and hydroxyethyl starches (HES) to overcome this problem (U.S. Pat. No. 5,945,272).
Since experimental work with mice has shown the use of serum to be no more effective than its sodium content (Rosenthal; cited by Fox, 1967) and the use of colloids serves both to raise venous pressure and to reduce sodium excretion, it should be possible to devise a salt-colloid mixture suitable for fluid replacement therapy.
It would therefore be advantageous if the colloid portion of a blood plasma expander could be a non-antigenic aqueous drug and virus-free solution which could act as an oncotic agent, which could serve as food for various tissue cells, which could be used for cryopreservation of tissues preparatory to transplantation, which could be freely miscible with other electrolytes, nutrients, oncotics, and oxygen bearing substances known in the blood transfusion art and which could be sterilized and stored long term for use at ambient room temperatures.
Accordingly, there is a critical and continual need for a blood plasma expander that can be used for volume deficiency shock, as an alleviant in anaphylactic and allergic shock, for replacing plasma lost after burns and as a result of diarrhea and for preserving and transporting organs.
OBJECTS OF THE INVENTION
Accordingly, it becomes an object of the invention to provide a salt-colloid mixture suitable as a blood plasma expander for all blood types, which does not have the drawbacks of plasma/albumin (problems with donor accessibility, possible viral infection, foreign antigens, cold storage), or the balancing of high and low molecular weight solutions of dextrans or hydroxyethyl starches.
Another object of the invention is to provide a novel agent useful as a blood and plasma expander by dint of molecular size large enough to allow it to maintain intravascular residence and osmotic pressure for a prolonged time.
Yet another object of the invention is to provide a blood and plasma expander which can serve as a source of nutrient growth factors for the cells it bathes.
A further object of the invention is to provide a useful blood and plasma expander which is miscible and compatible with all components of blood and is itself non-toxic, non-antigenic, and non-pyrogenic.
Still a further object of the invention is to provide a blood substitute and plasma expander which is stable under prolonged storage and is either safely discharged from the body or degraded to nutrient components.
Another object of the invention is to provide a blood-free plasma expander and blood substitute for use in a subject in need thereof, comprising a solution of alpha-keratose.
Yet another object of the invention is to provide a pharmaceutical composition useful as a blood plasma expander and blood substitute comprising a therapeutically effective amount of alpha-keratose that is soluble in aqueous and physiological fluids.
Another object of the invention is to provide a pharmaceutically acceptable carrier comprising a solution of alpha-keratose.
Yet another object of the invention is to provide a buffer comprising a solution of alpha-keratose.
Still another object of the invention is to provide a method of treating a human in need of blood by intravenously administering to the human an effective amount of a blood substitute comprising alpha-keratose.
Still yet another object of the invention is to provide a method for increasing the volume of the blood circulatory system wherein the method comprises transfusing into a system having a decreased volume, a quantity of a blood volume expander which consists of a solution of alpha-keratose, wherein the quantity is transfused in an effective amount to increase said volume.
Another object of the invention is to provide a method for the treatment of shock which comprises administering into the circulatory system of a mammal in shock, a blood plasma expander consisting of a solution of alpha-keratose, in an effective amount to alleviate said shock.
Yet another object of the invention is to provide a method for maintaining an isolated mammalian organ in a viable state which method comprises perfusing the organ with an effective amount of a perfusate consisting of a solution of alpha-keratose.
Another object of the invention is to provide an oncotic agent which has been shown to be a complete substitute for fetal calf serum in tissue cultured cells which have been adapted to growth in peptone dialysate.
Still another object of the invention is to provide a method for removing pathogens, poisons or toxins from blood present in a patient, the method comprising the steps of infusing the patient with a sufficient volume of a blood substitute solution comprising at least one water soluble oncotic agent while removing an equal volume of blood from the patient to reduce the hematocrit of the patient to 10 to 15%; separating the blood cells of the blood from the pathogens, toxins or poisons; resuspending the blood cells in a blood plasma expander comprising a water soluble oncotic agent to produce a blood cell comprising solution; and infusing the patient with the blood cell comprising solution; whereby the pathogens, toxins or poisons are removed from the blood of the patient.
The foregoing has outlined some of the pertinent objects of the present in
Holland & Knight LLP
Saucier Sandra
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