Liquid purification or separation – Processes – Liquid/liquid solvent or colloidal extraction or diffusing...
Reexamination Certificate
2001-03-23
2004-05-18
Kim, John (Department: 1723)
Liquid purification or separation
Processes
Liquid/liquid solvent or colloidal extraction or diffusing...
C210S321600, C210S651000, C422S044000, C514S001000, C514S002600, C604S004010, C604S005010, C604S005040
Reexamination Certificate
active
06736972
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to systems, methods, and devices used for hemofiltration. More specifically, the present invention relates to hemofiltration for reducing inflammatory mediator-related diseases (IMRD), which include systemic inflammatory response syndrome (“SIRS”), multiorgan system dysfunction syndrome (“MODS”), multiorgan system failure (“MOSF”),and compensatory anti-inflammatory response syndrome (CARS).
BACKGROUND
Patients with life threatening illness are cared for in hospitals in the intensive care unit (“ICU”). These patients may be seriously injured from automobile accidents, etc., have had major surgery, have suffered a heart attack, or may be under treatment for serious infection, cancer, or other major disease. While medical care for these primary conditions is sophisticated and usually effective, a significant number of patients in the ICU will not die of their primary disease. Rather, a significant number of patients in the ICU die from a secondary complication known commonly as “sepsis” or “septic shock”. Once again, the proper medical terms for sepsis and septic shock are systemic inflammatory response syndrome (“SIRS”), multiorgan system dysfunction syndrome
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(“MODS”), multiorgan system failure (“MOSF”),and compensatory anti-inflammatory response syndrome (CARS).
In short, medical illness, trauma, complication of surgery, and, for that matter, any human disease state, if sufficiently injurious to the patient, may elicit SIRS/MODS/MOSF or CARS. The systemic inflammatory response within certain physiologic limits is beneficial. As part of the immune system, the systemic inflammatory response promotes the removal of dead tissue, healing of injured tissue, detection and destruction of cancerous cells as they form, and mobilization of host defenses to resist or to combat infection. If the stimulus to the systemic inflammatory response is too potent, such as massive tissue injury or major microbial infection, however, then the systemic inflammatory response may cause symptoms which include fever, increased heart rate, and increased respiratory rate. This symptomatic response constitutes systemic inflammatory response syndrome (“SIRS”). If the inflammatory response is excessive, then injury or destruction to vital organ tissue may result in vital organ dysfunction, which is manifested in many ways, including a drop in blood pressure, deterioration in lung function, reduced kidney function, and other vital organ malfunction. This condition is known as multiorgan dysfunction syndrome (“MODS”). With very severe or life threatening injury or infection, the inflammatory response is extreme and can cause extensive tissue damage with vital organ damage and failure. These patients will usually die promptly without the use of ventilators to maintain lung ventilation, drugs to maintain blood pressure and strengthen the heart, and, in certain circumstances, artificial support for the liver, kidneys, coagulation, brain and other vital systems. This condition is known as multiorgan system failure syndrome (“MOSF). These support measures partially compensate for damaged and failed organs, they do not cure the injury or infection or control the extreme inflammatory response which causes vital organ failures.
In recent years, it is increasingly recognized that SIRS/MODS/MOSF exists in phases. In particular, an early pro-inflammatory phase, which is recognized as SIRS, usually occurring within hours or a very few days of significant injury or infection; and a later compensatory anti-inflammatory response syndrome (CARS) which occurs later (5-10 days). SIRS and CARS also appear in repeating and alternate cycles, or concurrently.
A s noted previously, the pro-inflammatory response is critical to host recovery and survival (by healing injury and eliminating infection), but when extreme this response causes vital organ dysfunction or failure. In biology, it is common for one response to be counter balanced by another response; these compensatory responses or systems allow restoration of balance and return the organism (e.g., the patient) to homeostasis. CARS is associated with the abatement of the excess IM characteristic of SIRS, however CARS itself is often extreme and results in immune suppression. SIRS and CARS are each associated with respective characteristic IM. The immune suppression of CARS is very commonly associated with secondary infection. This secondary infection then elicits another SIRS, often worse and more destructive than the first. In patients, it is commonly this second episode of SIRS which is lethal.
Both SIRS and CARS are mediated by excesses of either pro-inflammatory and anti-inflammatory mediators, respectively. Hemofiltration should be as beneficial to CARS as to SIRS. However, in SIRS the improvement should be affirmatively observed by improvement in pulmonary and cardio-circulatory function and survival, whilst in CARS it will be observed negatively, by non-occurrence of secondary infection and secondary SIRS. Both SIRS and CARS may be monitored in a limited way, by monitoring their respective IM in blood, lung or other body fluid.
Hemofiltration with a 100 to 150 kD filter is anticipated to remove the excess circulating IM which respectively characterize SIRS/MODS/MOSF, or CARS. During either condition, it may be desirable to actually supplement IM or provide some other therapeutic agent to augment the system in abatement. In particular, during SIRS/MODS/MOSF when pro-inflammatory IM are in excess, in addition to performance of hemofiltration to remove excess pro-inflammatory IM, the administration of anti-inflammatory IM or therapeutic agents may be useful to additionally abate or otherwise modulate the pro-inflammatory systemic inflammatory response. Similarly, during CARS hemofiltration is expected to remove excess anti-inflammatory IM which should ameliorate immune suppression, in addition, administration of pro-inflammatory IM or other therapeutic agent to promote immune responsiveness, should ameliorate immune suppression of CARS. What is sought is therapeutic synergy between large pore hemofiltration and administration of appropriate therapeutic agents.
In the United States of America each year, SIRS/MODS/MOSF afflicts approximately 400,000-600,000 patients and results in about 150,000 deaths. Overall, depending on the number of organ systems failing, the mortality rate of MOSF ranges generally from 40 to 100%. For instance, if three (3) or more vital organs fail, death results in more the 90% of cases. SIRS/MODS/MOSF and CARS are the most common cause of death in intensive care units and is the thirteenth most common cause of death in the United States of America. SIRS/MODS/MOSF and CARS cost about $5 to $10 billion yearly for supportive care. In addition, the incidence of SIRS/MODS/MOSF and CARS are on the rise; reported cases increased about 139% between 1979 and 1987. This increase is due to an aging population, increased utilization of invasive medical procedures, immuno-suppressive therapies (e.g. cancer chemotherapy) and transplantation procedures. (Morbidity and Mortality Weekly Report 1990; Detailed Diagnoses and Procedures, National Hospital Discharge Survey, 1993, from CDC/National 5 Center for Health Statistics, October/1995.)
The detrimental mechanism of SIRS/MODS/MOSF and CARS is the excessive activation of the inflammatory response. The inflammatory response consists of the interaction of various cell systems (e.g., monocyte/macrophage, neutrophil, and lymphocytes) and various humoral systems e.g., cytokine, coagulation, complement, and kallikrein/kinin). Each component of each system may function as an effector (e.g., killing pathogens, destroying tissue, etc.), a signal (e.g., most cytokines), or both. Humoral elements of the inflammatory response were known as toxic mediators, but are now known collectively as inflammatory mediators (“IM”). IM include various cytokines (e.g., tumor necrosis factor (“TNF”); the interleukins; interferon, etc.), various prostaglandins, various clotting factors
Baker & Botts L.L.P.
Immunocept, L.L.C.
Kim John
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