DE202019005458U1 - System for extracorporeal hyperthermia perfusion (EHP) therapy - Google Patents

Abstract

A system (10) for heating blood comprising:
a tube system (200) having at least one inlet (I) and at least one outlet (O), wherein the tube system (200) is configured such that it carries blood between the inlet (I) and the outlet (O), and
at least one heat transfer device (202) in fluid communication with the hose system (200) and configured to transfer heat to blood to increase the blood temperature (T2) within the hose system (200),
wherein the system (10) is configured so that it increases the body temperature of a person (20), which can be connected to the hose system (200), by taking blood from the person (20) through the at least one inlet (I) , the blood is conducted through the tube system (200) away from the at least one inlet (I) to the at least one heat transfer device (202) and the heated blood through the tube system (200) away from the at least one heat transfer device (202) to the at least an outlet (O) is passed to increase the body temperature (Temp1) by using heated blood as a heat transfer medium.

Description

The present invention relates to a system for heating blood, in particular for performing extracorporeal hyperthermia perfusion (EHP) therapy. The present invention further relates to extracorporeal blood above normal body temperature for use in the treatment of a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis. The present invention also relates to a combination of extracorporeal blood above normal body temperature and a chemotherapeutic agent for use in the treatment of cancer.

BACKGROUND OF THE INVENTION

For decades, cancer has been the leading cause of death, the incidence of which is increasing every day. Cancer can be treated through surgery, chemotherapy, radiation therapy, hormone therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy), and synthetic lethality. The choice of therapy depends on the location and grade of the tumor and the stage of the disease, as well as the general condition of the patient (performance status). A number of experimental cancer treatments are also under development. According to current estimates, two in five people will develop cancer at some point in their lives.

Hyperthermia is also a well known technique for treating cancer. Even in ancient times, medicine men used heat treatment to cure people of various ailments and diseases. By using plants, they created a fever in the patient so that the patient's body could defend itself against viruses and bacteria. More than a hundred years ago, doctors treating cancer patients discovered that some patients who had developed a fever themselves had spontaneous tumor regression or even remissions. This led to the conclusion that cancer cells were more sensitive to heat than healthy cells. To date, various methods and devices have been developed to such an extent that various targeted applications have become possible in medical practice.
Hyperthermia has the advantage that it neglects or avoids the use of chemicals or harmful radiation. The increased body temperature can damage the cancer cells with minimal damage to normal cells. Hyperthermia can also be combined with radiation therapy and / or chemotherapy to improve cancer treatment. Numerous clinical studies have examined hyperthermia in combination with radiation therapy and / or chemotherapy. These studies have focused on the treatment of different types of cancer. Many of these studies have shown a significant reduction in tumor size when the hyperthermia is combined with other treatments.

In the past, thermal treatment of cancer was usually limited to superficial cancers. In the clinical application of hyperthermia, three methods can be distinguished: local, regional and whole-body hyperthermia. What these methods have in common is that, for the treatment of tumors, individual body parts or body regions can be heated to a temperature between 40 ° and 44 ° C with external electromagnetic waves, depending on the indication.

Local hyperthermia is a procedure in which heat is applied to a small area, e.g. a tumor in a tissue, is applied using various techniques that apply heat energy to the tumor. Microwaves, ultrasound or radio frequency can be used for this purpose. In regional hyperthermia, a part of the body, e.g. a limb or organ, warmed up. The body part can be heated with the aid of antenna arrays using various applicators. The sigma blade applicator is a widely used applicator that contains four pairs of dipole antennas in a ring around the patient. Whole body hyperthermia is usually used to treat metastatic tumors that have spread throughout the body. The procedure is possible with the help of sedation under general anesthesia. A patient's body temperature can be raised from the outside of the body by using thermal blankets, warm water immersion (the patient is placed in warm water), or thermal chambers (similar to large incubators). Side effects of local hyperthermia can include pain at the target site, bleeding, blood clots, infection, swelling, burns, blistering and / or damage to the skin, nerves and muscles around the treated area. Side effects of regional and whole-body hyperthermia can include nausea, vomiting and / or diarrhea. In severe cases, it leads to problems related to the heart, blood vessels and other important organs. The main disadvantage of whole-body heating is the systemic stress that results from a lack of preferential heating and the need for anesthesia with its negative side effects and risks.

In addition, the number of therapy-resistant diseases, especially in the field of autoimmune diseases, infectious diseases, inflammatory diseases and sepsis, has increased in recent years.

On the basis of the above, there is a need for a new device or system that enables the therapy of cancer, autoimmune diseases, infectious diseases, inflammatory diseases and / or sepsis, in particular by heating the blood. This therapy should be carried out with as few side effects as possible - but still effective.

The present inventor found that the heating of the patient's blood itself, rather than the application of external heat to the patient, enables cancer, autoimmune diseases, infectious diseases, inflammatory diseases and sepsis to be treated effectively with few side effects. As a result, the present inventor has developed an improved device or system for removing the patient's blood from the circulation, heating that blood and returning it to the patient's body. This system also enables highly efficient blood purification and supply of the organism with the necessary natural or chemical substances. It also allows blood cleansing, oxygen therapy, mild chemotherapy, mild radiation therapy, and / or surgery to be combined in one procedure / therapy approach, which is most effective in treating cancer. The present inventor also found out that heat treatment of the blood could increase the therapeutic success of an operation, radiation and / or chemotherapy in cancer patients. The inventor also provides extracorporeal blood above normal body temperature for use in treating a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease, and sepsis.

SUMMARY OF THE INVENTION

• ein Schlauchsystem mit mindestens einem Einlass und mindestens einem Auslass, wobei das Schlauchsystem so konfiguriert ist, dass es Blut zwischen dem Einlass und dem Auslass führt, und
• mindestens eine Wärmeübertragungsvorrichtung, die so konfiguriert ist, dass sie Wärme auf Blut überträgt, um die Bluttemperatur innerhalb des Schlauchsystem zu erhöhen,
• wobei das System so konfiguriert ist, dass es die Körpertemperatur einer Person, die mit dem Schlauchsystem verbunden werden kann, erhöht, indem Blut der Person durch den mindestens einen Einlass aufgenommen wird, das Blut durch das Schlauchsystem weg von dem mindestens einen Einlass zu der mindestens einen Wärmeübertragungsvorrichtung geleitet wird und das erwärmte Blut durch das Schlauchsystem weg von der mindestens einen Wärmeübertragungsvorrichtung zu dem mindestens einen Auslass geleitet wird, um die Körpertemperatur durch Verwendung von erwärmtem Blut als Wärmeübertragungsmedium zu erhöhen.

In a first aspect, the present invention relates to a system for heating blood, preferably configured to carry out a method according to the fourth to seventh aspects, comprising:

• a tube system having at least one inlet and at least one outlet, the tube system configured to carry blood between the inlet and the outlet, and
• at least one heat transfer device configured to transfer heat to blood in order to increase the blood temperature within the hose system,
• wherein the system is configured to increase the body temperature of a person who can be connected to the tube system by taking blood from the person through the at least one inlet, the blood through the tube system away from the at least one inlet to the at least a heat transfer device and the heated blood is passed through the tubing system away from the at least one heat transfer device to the at least one outlet to increase the body temperature by using heated blood as a heat transfer medium.

In a second aspect, the present invention relates to extracorporeal blood above normal body temperature for use in the treatment of a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.

In a third aspect, the present invention relates to a combination of extracorporeal blood above normal body temperature and a chemotherapeutic agent for use in the treatment of cancer.

This summary of the invention does not necessarily describe all of the features of the present invention. Other embodiments will emerge from a review of the detailed description that follows.

DESCRIPTION

Definitions

Before the present invention is described in detail below, it should be made clear that this invention is not limited to the specific methodology described herein or is limited to the specific protocols and reagents described herein, since these can vary. It is also to be understood that the terminology used herein is used only for the purpose of describing particular embodiments and is not intended to limit the scope of the present invention, which is limited only by the appended claims. Unless otherwise defined herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

The terms used herein are preferably defined as in "A multilingual glossary of biotechnological terms: (IUPAC Recommendations)", Leuenberger, HGW, Nagel, B. and Kölbl, H. Hrsg. (1995), Helvetica Chimica Acta, CH- 4010 Basel, Switzerland).

Various documents are cited throughout the text of this specification. Each of the documents cited herein (including all patents, patent applications, scientific publications, manufacturer specifications, instructions, GenBank accession number, sequence filings, etc.), either supra or infra, are incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention would not precede any such disclosure by virtue of any prior invention. In the event of a conflict between the definitions or teachings of such incorporated references and definitions or teachings reproduced in this specification, the text of this specification takes precedence.

The term “comprise” and variations such as “comprises” and “comprising” according to the present invention mean the inclusion of a specified number or specified group of numbers but not the exclusion of any other number or any group of numbers. According to the present invention, the term “consisting essentially of” means the inclusion of a specified number or a group of numbers, with modifications or other numbers that would significantly influence or change the specified number being excluded. The term “consisting of” or variations such as “consists of” means according to the present invention the inclusion of a specified number or group of numbers and the exclusion of any other number or group of numbers.

The terms “a” and “an” and “the” and similar references that are used in connection with the description of the invention (in particular in connection with the claims) are to be interpreted in such a way that they contain both the singular and the also include the plural, unless otherwise stated herein or clearly contradicted by the context.

The term “hemoperfusion / hemoperfusion” as used here refers to a process of filtering blood extracorporeally (ie outside the body) in order to remove one or more toxins. As with other extracorporeal procedures, such as hemodialysis (HD), hemofiltration (HF), and hemodiafiltration (HDF), the patient's blood enters a machine, is filtered, and then returns to the patient, typically via a venous access (from out and back into a vein). During the extracorporeal process, inflammatory and other harmful molecules are removed from the blood of a patient's organism. Adsorbers (filters), in particular macroporous resin beads, are preferably used, which enable effective blood purification. These adsorbers, in turn, can be combined with other therapy components that regulate the metabolism and strengthen the immune system. That way, drug strategies can be more effective.
The present inventor worked with adsorbers which, for example, can eliminate heavy metal loads in just one treatment, whereby EHP is as effective as a large number of chelate infusions over a long period of time. The heavy metals are released from the tissues into the blood, and the heat maximizes this process. The heavy metals are then filtered out of the blood by the adsorbers without being reabsorbed in the kidneys. This increases the effectiveness to a maximum.
Other adsorbers can be used to eliminate sepsis, severe inflammation, cytokines, toxins, and pesticides or drugs. Special adsorbers can also be used for Lyme disease, autoimmune diseases, cancer, suspected multi-organ failure, liver and kidney diseases, systemic inflammatory response syndrome (SIRS) or lung diseases such as ARDS (acute respiratory distress syndrome).

The term "hyperoxygenated hemoperfusion / hemoperfusion" as used here refers to the hemoperfusion / hemoperfusion as described above, but expanded to include an oxygenator. This increases the oxygen content of the blood massively. The technology of hyperoxygenated hemoperfusion / hemoperfusion originally comes from cardiac surgery, but is now also used in other therapeutic disciplines. By supplying medical oxygen, it is possible to achieve a physical oxygen saturation of at least 400%, 500%, 600% or 700%, preferably of at least 700%, in the tissue. In this way, the body's own repair and regeneration processes can be restarted. In addition, the formation of new blood vessels is stimulated and toxins can be better removed from the organism.

As used herein, the term “hyperthermia” refers to a type of medical treatment that involves exposing body tissues to higher temperatures to treat cancer. This is achieved through the use of radio or electromagnetic waves that heat the areas of the organism to be treated to between 40 ° C and 44 ° C, depending on the indication. The term hyperthermia treatment includes all procedures with which areas of the body are heated in a targeted and controlled manner.

Hyperthermia has the advantage that it spares or avoids the use of chemicals or harmful radiation. The increased body temperature can damage the cancer cells with minimal damage to normal cells. Hyperthermia can also be combined with radiation therapy and / or chemotherapy to improve cancer treatment. Numerous clinical studies have examined hyperthermia in combination with radiation therapy and / or chemotherapy. These studies have focused on the treatment of different types of cancer. Many of these studies have shown a significant reduction in tumor size when the hyperthermia is combined with other treatments. This effect is synergistic.

In the clinical application of hyperthermia, three methods can be distinguished: local, regional and whole-body hyperthermia. Local hyperthermia is a procedure in which heat is applied to a small area, e.g. a tumor in tissue, using various techniques that deliver thermal energy to the tumor. Microwaves, ultrasound or radio frequency can be used for this purpose. In regional hyperthermia, a part of the body, e.g. a limb or organ, warmed up. The body part can be heated with the aid of antenna arrays using various applicators. Whole body hyperthermia is usually used to treat metastatic tumors that have spread throughout the body. The procedure is possible with the help of sedation under general anesthesia. A patient's body temperature can be raised from the outside of the body by using thermal blankets, warm water immersion (the patient is placed in warm water), or thermal chambers (similar to large incubators). Side effects of local hyperthermia can include pain at the target site, bleeding, blood clots, infection, swelling, burns, blistering and / or damage to the skin, nerves and muscles around the treated area. Side effects of regional and whole-body hyperthermia can include nausea, vomiting and / or diarrhea. In severe cases, it leads to problems related to the heart, blood vessels and other important organs. The main disadvantage of whole-body heating is the systemic stress that results from a lack of preferential heating and the need for anesthesia with its negative side effects and risks.

The term "hemo- / hemo-hyperthermia", as used here, refers to a technique that does not heat the organism from the outside, but heats the blood itself, e.g. to 39.0 to 44.0 ° C, preferably to 40.0 to 42.5 ° C. In this form of therapy, blood is taken from the patient's bloodstream. The extracorporeal blood is heated, e.g. to a temperature between 39.0 and 44.0 ° C., preferably to a temperature between 40.0 and 42.5 ° C., and the heated blood is then returned to the patient's bloodstream. With the help of hemo- / hemo-hyperthermia, overall warming of the organism is achieved from within.

The term “extracorporeal hyperthermia perfusion therapy (EHP)” as used here refers to a combination of “(hyperoxygenated) hemohyperthermia / hemohyperthermia” and “perfusion therapy”. With the help of special catheters in cancer therapy, a) cytostatics / chemotherapeutic agents in significantly lower concentrations than with conventional chemotherapy can often even be sent directly to the affected target organs and b) at the same time the excess of cytostatics / chemotherapeutic agents can be removed from the organism at the end of the therapy are excreted, so that with improved effectiveness of the cytostatics there are almost no side effects. EHP therapy has few side effects and is usually well tolerated by the patient. The EHP therapy is preferably used as an adjunct to Chemotherapy and / or radiation therapy are used. In other words, EHP therapy is preferably used in combination with chemotherapy and / or radiation therapy.

EHP therapy can be used to treat cancer, numerous chronic diseases, autoimmune diseases such as rheumatism / rheumatic diseases, diseases resulting from massive heavy metal exposure, infectious diseases such as borreliosis, inflammatory diseases such as atherosclerosis or the systemic inflammatory response syndrome (SIRS), sepsis, diseases associated with increased Cholesterol levels, lung diseases, liver diseases such as acute respiratory distress syndrome (ARDS) and / or kidney diseases. EHP therapy is preferably used for the treatment of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and / or a sepsis.

As used herein, the term “disease” refers to an abnormal condition affecting an individual's body. A disease is often understood as a medical condition that is associated with specific symptoms and signs. Disease can be caused by factors that originally came from an external source, such as an infectious disease, or it can be caused by internal dysfunction such as an autoimmune disease. In humans, the term “disease” is often broadly defined to refer to any medical condition that causes pain, dysfunction, anxiety, social problems or death, or similar problems to those who come in contact with the person. In this broader sense, it sometimes includes injuries, disabilities, disorders, syndromes, infectious, isolated symptoms, deviant behaviors, and atypical variations in structure and function, while in other contexts and for other purposes these may be viewed as distinguishable categories. Illnesses usually affect people not only physically, but also emotionally, since falling ill and living with many diseases can change one's perspective in life and personality. In connection with the present invention, the disease is selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.

As used herein, the term "autoimmune disease" refers to any condition in which the body produces an immunogenic (i.e., affecting the immune system) response to a part of its own tissues. In other words, the immune system loses its ability to recognize a particular tissue or system within the body as its own and attacks it as if it were foreign. Autoimmune diseases can be divided into those in which one organ is predominantly affected (e.g. hemolytic anemia and antiimmune thyroiditis) and those in which the process of the autoimmune disease diffuses through many tissues (e.g. systemic lupus erythematosus). For example, it is believed that multiple sclerosis is caused by T cells attacking the sheaths that surround the nerve fibers in the brain and spinal cord. This leads to loss of coordination, weakness and blurred vision. Autoimmune diseases are known in the art and include e.g. Hashimoto's thyroiditis, Graves' disease, lupus, multiple sclerosis, rheumatism / rheumatic diseases, e.g. rheumatoid arthritis, hemolytic anemia, anti-immune thyroiditis, systemic lupus erythematosus, celiac disease, Crohn's disease, colitis, diabetes, scleroderma, psoriasis and the like. Rheumatic diseases caused by autoimmunity include, for example, but not limited to, ankylosing spondylitis, recurrent polychondritis, systemic lupus erythematosus, rheumatoid arthritis, gout, inflammatory arthritis, pseudogout, juvenile arthritis, Sjogren's syndrome, scleroderma, disorder, polymyatoma and psoriatic arthritis.

The term "infectious disease" as it is used here refers to any disease that can be transmitted from person to person or from organism to organism and is caused by a microbial pathogen (e.g. cold). Infectious diseases are known in the art and include e.g. a viral disease, bacterial disease, or parasitic disease. The diseases mentioned are caused by a virus, a bacterium or a parasite. It can e.g. Borreliosis, hepatitis, sexually transmitted diseases (e.g. chlamydia or gonorrhea), tuberculosis, human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS), diphtheria, hepatitis B, hepatitis C, cholera, severe acute respiratory syndrome (SARS) Act, bird flu and influenza. The infectious disease is preferably borreliosis.

As used herein, the term “inflammatory disease” refers to a condition in which the immune system attacks the body's own tissues and causes inflammation. Preferably, the inflammatory disease from the group consisting of atherosclerosis, an autoimmune disease, Allergy, asthma, celiac disease, glomerulonephritis, hepatitis and inflammatory bowel disease. The autoimmune disease is further specified above.

The term "sepsis" as used here refers to a life-threatening condition that occurs when the body's response to infection causes damage to its own tissues and organs. Sepsis is usually caused by an inflammatory immune response triggered by an infection. Mostly it is a bacterial infection, but it can also be caused by fungi, viruses or protozoa. The severity of the disease partly determines the outcome of the sepsis. The risk of dying from sepsis is up to 30%, from severe sepsis up to 50% and from septic shock up to 80%.

The terms "cancer" or "cancer" as used herein refer to or describe the physiological condition of an individual who is typically characterized by unregulated cell growth. Examples of cancers include carcinoma, lymphoma, blastoma, sarcoma, and leukemia. Examples of such cancers are in particular bone cancer, blood cancer, lung cancer, liver cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast cancer, prostate cancer, cancer of the uterus - and reproductive organs, Hodgkin's disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid, cancer of the parathyroid, cancer of the adrenal gland, soft tissue sarcoma, bladder cancer, kidney cancer, renal cell carcinoma, renal pelvic cancer, cancer of the central nervous system, neoplasia of the neoplasm Spinal axis tumors, gliomas, meningiomas, and pituitary adenomas. According to the invention, the term “cancer” also includes cancer metastases.

The terms “individual” and “subject” can be used interchangeably here. The individual or subject can be any mammal, including both human and other mammals, e.g. one animal. Human individuals or subjects are particularly preferred. The individual can be a patient.

As used herein, the term “patient” refers to any subject suffering from a disease, particularly cancer, an autoimmune disease, an infectious disease, an inflammatory disease and / or sepsis. The patient can be treated and / or the response to that treatment can be assessed. The patient can be any mammal, including both human and other mammals, e.g. one animal. Human subjects as patients are particularly preferred.

The term “treatment”, in particular “therapeutic treatment” as used here, refers to any therapy that improves the state of health and / or extends (increases) the life span of a patient. Such therapy can eliminate the disease in a patient, halt or slow the development of a disease in a patient, inhibit or slow the development of a disease in a patient, reduce the frequency or severity of symptoms in a patient, and / or that Reduce the recurrence of disease in a patient who currently has or previously had a disease.

One drug used in chemotherapy is a chemotherapy drug. As used herein, the term “chemotherapeutic agent” refers to a compound that is administered in the treatment of cancer. These active substances or drugs are categorized according to their mode of action within a cell, e.g. whether and at what stage they influence the cell cycle. Alternatively, an active ingredient can be characterized on the basis of its ability to crosslink DNA directly, to intercalate into DNA, or to induce chromosomal and mitotic aberrations by affecting nucleic acid synthesis. The chemotherapeutic agent is preferably selected from the group consisting of alkylating agents, anthracyclines, cytoskeletal disruptors, epothilones, histone deacetylase inhibitors, inhibitors of topoisomerase I, inhibitors of topoisomerase II, kinase inhibitors, nucleotide analogs and precursor analogs, agents based on peptide antibiotics and retinoids selected.

As used herein, the term “radiation therapy (also called radiation therapy)” refers to a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. At low doses, the radiation is used in X-rays to get inside the body. At high doses, radiation therapy kills cancer cells or slows their growth by damaging their DNA. Cancer cells whose DNA is irreparably damaged stop dividing or die. When the damaged cells die, they are broken down and out of the body away. Radiation therapy doesn't kill cancer cells immediately. It takes days or weeks of treatment for the DNA to become so damaged that the cancer cells die. Then the cancer cells continue to die weeks or months after the end of radiation therapy.

As used herein, the term "normal body temperature (also known as normothermia or euthermia)" refers to the typical temperature found in a person. In humans, the normal body temperature is 37 ° C. However, this value is only an average. The normal body temperature can be slightly higher or lower. A number of factors can affect body temperature, including age, gender, time of day, and level of activity. In infants and children, for example, the average body temperature is between 36.6 ° C and 37.2 ° C. In adults, the average body temperature is between 36.1 ° C and 37.2 ° C. The normal human body temperature range is therefore typically reported in humans as 36.1 ° C to 37.5 ° C, e.g. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3 , 37.4 or 37.5 ° C.

As used herein, the term “extracorporeal blood” refers to blood drawn / isolated from a person's bloodstream.

As used herein, the term "extracorporeal circuit" refers to a procedure in which blood is drawn from an individual's circulation in order to subject it to a process before it is returned to the circulation. The entire system that transports blood outside the body is called the extracorporeal circuit. In connection with the present invention, the blood is warmed / heated above normal body temperature before it is returned to the circulation. In preferred embodiments, the blood is not only warmed / warmed above normal body temperature, but it is also oxygenated, filtered and / or with therapeutic agents such as e.g. Chemotherapy drugs, added before it is put back into the circulation.

As used herein, the term "systemic administration" refers to the administration of the therapeutic agent, e.g. of a chemotherapeutic agent, so that this active ingredient is widely distributed in a patient's body in significant quantities and has a biological effect. Typical systemic routes of administration are administration by incorporation of the therapeutic agent, e.g. of the chemotherapeutic agent, directly into the vasculature, or by oral, pulmonary or intramuscular administration, the therapeutic agent, e.g. the chemotherapeutic agent, enters the vascular system and is transported via the blood to one or more desired target (s). Systemic administration can be by parenteral administration. As used herein, the term "parenteral administration" refers to the administration of the therapeutic agent, e.g. of the chemotherapy drug so the compound doesn't pass through the gut. The term “parenteral administration” includes, but is not limited to, intravenous administration, subcutaneous administration, intradermal administration, or intra-arterial administration.

Embodiments of the invention

As mentioned above, the present inventor found that the heating of the patient's blood itself and not by applying heat to the patient from outside enables an effective treatment of cancer, autoimmune diseases, infectious diseases, inflammatory diseases and / or sepsis with few side effects .

• 1. Die Temperatur zwischen 40°C und 44°C beeinflusst bestimmte Proteine in den Krebszellen, die für die Bildung von essentiellen Enzymen für die Zellfunktion notwendig sind. Ihre Zerstörung kann die Apoptose der Krebszellen auslösen.
• 2. Die Erwärmung des Blutes führt auch zu einer Verstopfung der Blutgefäße im Bereich des Tumors. Dadurch gelangen weniger Sauerstoff und Nährstoffe in die Krebszellen.
• 3. Der Hitzeschock bewirkt, dass die Krebszellen als Abwehrreaktion verschiedene „Hitzeschockproteine“ (HSP) bilden. Die Proteine, die sich an den äußeren Zellmembranen befinden, schützen die Krebszellen vor den hohen Temperaturen und werden vom körpereigenen Immunsystem zunächst nicht erkannt. Durch die kontinuierliche Hitzebehandlung werden diese Proteine jedoch zerstört, und die nicht maskierten Krebszellen werden dann vom Immunsystem eliminiert. Darüber hinaus erhöht die Wärme die Durchblutung des Tumors und damit die gezielte Aufnahme von Medikamenten und Wirkstoffen.
• 4. Blutgefäße innerhalb von Tumoren sind in der Regel extrem dünn und so verzweigt, dass die Durchblutung nur langsam erfolgen kann. So bleibt die Wärme auch nach Beendigung der Behandlung noch vergleichsweise lange im Tumorgewebe und kann ihre Wirkung noch entfalten.

In particular, the present inventor found that heating the patient's blood even to a temperature between 40 ° C and 44 ° C in cancer therapy has the following advantages:

• 1. The temperature between 40 ° C and 44 ° C influences certain proteins in the cancer cells that are necessary for the formation of enzymes essential for cell function. Their destruction can trigger apoptosis of the cancer cells.
• 2. The warming of the blood also leads to a blockage of the blood vessels in the area of the tumor. As a result, less oxygen and nutrients reach the cancer cells.
• 3. The heat shock causes the cancer cells to produce various "heat shock proteins" (HSP) as a defense reaction. The proteins, which are located on the outer cell membranes, protect the cancer cells from the high temperatures and are initially not recognized by the body's immune system. However, the continuous heat treatment destroys these proteins, and they don't masked cancer cells are then eliminated by the immune system. In addition, the heat increases the blood flow to the tumor and thus the targeted absorption of drugs and active ingredients.
• 4. Blood vessels within tumors are usually extremely thin and so branched that the blood flow is slow. The heat remains in the tumor tissue for a comparatively long time even after the treatment has ended and can still develop its effect.

As a result, the present inventor has developed an improved device or system for removing the patient's blood from the circulation, heating that blood and returning it to the patient's body. This system also enables highly efficient blood purification and supply of the organism with the necessary natural or chemical substances. It also allows blood cleansing, oxygen therapy, mild chemotherapy, mild radiation therapy, and / or surgery to be combined in a procedure / therapy approach that is most effective in treating cancer.

The methods can use the system or its embodiments as discussed above. Thus, the features, advantages and technical effects that apply to the system and its embodiments can also apply to the methods and other aspects and vice versa.

• - ein Schlauchsystem mit mindestens einem Einlass und mindestens einem Auslass, wobei das Schlauchsystem so konfiguriert ist, dass es Blut zwischen dem Einlass und dem Auslass führt, und
• - mindestens eine Wärmeübertragungsvorrichtung, die so konfiguriert ist, dass sie Wärme auf das Blut überträgt, um die Bluttemperatur innerhalb des Schlauchsystems zu erhöhen.

The system can include:

• a tube system having at least one inlet and at least one outlet, the tube system being configured such that it carries blood between the inlet and the outlet, and
• - At least one heat transfer device which is configured to transfer heat to the blood in order to increase the blood temperature within the hose system.

The system can be configured to increase the body temperature of a person who can be connected to the tube system by taking in blood from the person through the at least one inlet, the blood through the tube system away from the at least one inlet to the at least one a heat transfer device and the heated blood is passed through the tubing system away from the at least one heat transfer device to the at least one outlet to increase the body temperature by using heated blood as a heat transfer medium.

Therefore, the body must not be heated directly from the outside, but must be heated from the inside via the blood vessels in the body. This is in contrast to the classic hyperthermia procedure and enables new treatment methods. In the proposed system, heat is transported from the outside of the body to the inside of the body using blood as the carrier medium.

• ein Schlauchsystem mit mindestens einem Einlass und mindestens einem Auslass, wobei das Schlauchsystem so konfiguriert ist, dass es Blut zwischen dem Einlass (I) und dem Auslass (O) führt, und
• mindestens eine Wärmeübertragungsvorrichtung, die in Fluidverbindung mit dem Schlauchsystem steht und so konfiguriert ist, dass sie Wärme auf Blut überträgt, um die Bluttemperatur innerhalb des Schlauchsystem zu erhöhen,
• wobei das System so konfiguriert ist, dass es die Körpertemperatur einer Person, die mit dem Schlauchsystem verbunden werden kann, erhöht, indem Blut der Person durch den mindestens einen Einlass aufgenommen wird, das Blut durch das Schlauchsystem weg von dem mindestens einen Einlass zu der mindestens einen Wärmeübertragungsvorrichtung geleitet wird und das erwärmte Blut durch das Schlauchsystem weg von der mindestens einen Wärmeübertragungsvorrichtung zu dem mindestens einen Auslass geleitet wird, um die Körpertemperatur durch Verwendung von erwärmtem Blut als Wärmeübertragungsmedium zu erhöhen.

Accordingly, in a first aspect, the present invention relates to a system for heating blood, preferably configured to carry out a method described / claimed herein, comprising:

• a tube system with at least one inlet and at least one outlet, wherein the tube system is configured so that blood is drawn between the inlet ( I. ) and the outlet ( O ) leads, and
• at least one heat transfer device that is in fluid communication with the hose system and is configured to transfer heat to blood in order to increase the blood temperature within the hose system,
• wherein the system is configured to increase the body temperature of a person who can be connected to the tube system by taking blood from the person through the at least one inlet, the blood through the tube system away from the at least one inlet to the at least a heat transfer device and the heated blood is passed through the tubing system away from the at least one heat transfer device to the at least one outlet to increase the body temperature by using heated blood as a heat transfer medium.

The heat transfer device can be in fluid communication with the hose system. The inlet can be located, for example, in the left femoral vein or connected to it. The exit can, for example, be in the right femoral vein or be connected to it. Alternatively, the right femoral vein can be connected to the inlet and the left femoral vein to the outlet of the tube system. Jugular veins can also be used instead of the femoral veins. In addition, more than one inlet point and / or more than one outlet point can be used. It can also other locations on the blood vessels can be used to connect the inlet and outlet to the person's blood system or to the animal's blood system.

The subject can be a patient who has a disease, e.g. Cancer, an autoimmune disease, an infectious disease, an inflammatory disease and / or sepsis, and which requires treatment with the proposed system. The subject can be a person, i.e. be an individual, or an animal, preferably a mammal.

The hose system can consist of flexible or rigid hoses. T-pieces, valves, preferably three or four-way valves, can be used to adapt the hose system to the needs.

Body temperature can be increased throughout the body, in at least 50 percent of the volume or percent of the mass of the body, or in at least 75 percent of the volume or percent of the mass of the body. However, more local treatments of the body with the system, the procedures and the other aspects are also possible. For example, it is possible to heat less than 30 percent of the volume or percent of the mass of the body or less than 20 percent of the volume or percent of the mass of the body, e.g. only the tissue around a specific organ. This can be achieved by appropriate placement of the inlet and outlet of the system.

The system can be configured to increase body temperature by at least 0.5 ° C, by at least 1 ° C, by at least 2 ° C, or by at least 3 ° C. The normal body temperature of a person is between 36.1 ° C and 37.5 ° C, e.g. B. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0, 37.1, 37.2, 37.3, 37.4 or 37.5 ° C. An increase in body temperature to at least 38, 38.5, 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5 ° C or 44 ° C is possible his. Preferably the body temperature is increased to 40 ° C to 44 ° C. The body temperature is preferably increased to 40 to 42.5 ° C. However, the method can also be used when the body temperature is higher, i.e. the person has a fever or a higher temperature by other methods, e.g. by exogenous pyrogens. The increase in body temperature achieved by using the system can be less than 5 ° C.

The system can comprise at least one blood pump that is connected to the hose system. The pump can be a roller pump that generates a pulsation from the outside on a hose, i. E. H. a peristaltic pump, or another suitable pump, e.g. B. diaphragm pumps, piston pumps, centrifugal pumps. A centrifugal pump can be used when an oxygenator device is used to achieve higher pressures and achieve higher pumping power, e.g. compared to the pressure or the performance of a peristaltic pump.

The heat transfer device may comprise a heat exchanger which is configured so that an additional liquid, preferably water, is used, preferably an additional liquid having a temperature in the range from 42 ° C to 47 ° C or in the range from 44 ° C to 46 ° C or with a temperature of 45 ° C. The system can be configured so that the flow rate of the additional liquid through the heat exchanger can be greater than 2.5 liters per minute, preferably greater than 5 liters per minute. The temperature changes are comparatively slow when an additional liquid is used, e.g. compared to an electric heater. By using the additional liquid, it is possible in a simple manner to prevent overheating, which would be dangerous for the health of the person. An example of a heat transfer device is the CSC14 heat exchanger from LivaNova, formerly Sorin Group. However, other heat transfer devices can also be used. There can be a reservoir for the additional liquid and a circular flow of the additional liquid. The flow of the additional liquid can be generated by a pump for pumping the additional liquid. A heater can heat the additional liquid to a suitable temperature, preferably an electric heater. The heat exchanger can be a plate heat exchanger or a tubular heat exchanger or any other suitable device.

Alternatively, the heat transfer device can comprise an electrical heater. There may be a circuit to prevent the blood from overheating or heating up too quickly.

The system may include an oxygenator device configured to deliver additional oxygen to the blood carried through the tubing system. The oxygenator device can contain an inlet connection for oxygen. The combination of warming the blood and enriching the blood with oxygen offers the possibility of better medical treatments for many Diseases. An example of an oxygenator device is the Inspire 8F or 8FM oxygenator from LivaNova, formerly the Soring Group. However, other oxygenator devices can also be used. The oxygenator device can be fluidically connected to the hose system.

The oxygenator device can comprise the heat transfer device, preferably as an integral part. There may be a physical separation between the system of make-up fluid used for warming or warming up and the system of blood circulating within the oxygenator device. The heat exchanger within the oxygenator device may be a plate heat exchanger or a tubular heat exchanger or any other suitable device.

The system may comprise at least one adsorber unit having an inlet that is in fluid communication with the tubing system and an outlet that is in fluid communication with the tubing system, wherein the blood at the outlet has been filtered compared to the blood at the inlet. The adsorber unit can comprise an adsorber, preferably for the adsorption of inflammation molecules, toxic molecules and / or other harmful molecules. The adsorber unit can e.g. be an adsorber unit from Biosun or Biosky, i.e. a disposable MG series hemoperfusion cartridge. Additionally or alternatively, a dialysis machine can be used, preferably to remove small-molecule toxins. Filtering the blood can also have the technical effect of removing particles that originate from the system itself, e.g. Particles rubbed off by parts of the system.

The combination of heating the blood, adding oxygen and filtering can lead to very good results in the treatment of a disease, e.g. in cancer, an autoimmune disease, an infectious disease, an inflammatory disease and / or sepsis. The self-healing powers of the patient can be increased considerably by this combination. In addition, the adsorber units and / or adsorbers within the adsorber units can be individualized to the person and / or to the illness of the person. This may allow further improvements to the system in terms of the results of the treatment performed with the system.

The system can include a control unit. The control unit can be configured to control the heat generated or transferred by the heat transfer device and / or the control unit can be configured to control the heat that is transferred from the blood within the tubing system to or from the person's body The body of the animal is transferred, preferably by adjusting the flow rate of the blood within the tube system. Adjustments to the heat transfer of the heat transfer device are e.g. by changing the temperature of an additional liquid, which is used to warm the blood, and / or by changing the flow rate of the additional liquid. Alternatively, it is possible to adjust the electrical energy of an electrical heater used within the heat transfer device. In either case, the heat transfer can also depend on the rate of blood flow within the system. This flow rate can also be adjusted by the control unit in order to regulate the heat transfer.

Alternatively, no control device may be used and the system can be operated manually, e.g. by a technician, preferably a cardio technician, supervised by a doctor. However, the doctor can also operate the system manually.

• - eine Eingabefunktionalität zur Einstellung einer Zieltemperatur (TT2) des Blutes innerhalb des Systems (10), vorzugsweise im Bereich von 39 °C bis 44 °C, vorzugsweise im Bereich von 40 °C bis 44 °C, bevorzugter im Bereich von 40 °C bis 42,5 °C, und/oder
• - eine Eingabefunktionalität zur Einstellung einer Zieltemperatur (TT1) des Körpers, vorzugsweise im Bereich von 38 °C bis 44 °C, vorzugsweise im Bereich von 40 °C bis 44 °C, bevorzugter im Bereich von 40 °C bis 42,5 °C, und/oder
• - eine Eingabefunktionalität zur Einstellung einer Zielflussrate (TFR) des Blutes, vorzugsweise im Bereich von 1 Liter pro Minute bis 5 Liter pro Minute, vorzugsweise im Bereich von 2 Liter pro Minute bis 4 Liter pro Minute, bevorzugter im Bereich von 1,5 Liter pro Minute bis 3 Liter pro Minute, und/oder
• - eine Eingabefunktionalität zum Festlegen einer Zielzeit (Tt1) für den Betrieb des Systems (10), vorzugsweise innerhalb eines Bereichs von 1 Stunde bis 8 Stunden, vorzugsweise innerhalb des Bereichs von 2 Stunden bis 6 Stunden, bevorzugter innerhalb des Bereichs von 3 Stunden bis 5 Stunden.

The system can include at least one, any combination, or all of the following features:

• - an input functionality for setting a target temperature ( TT2 ) of the blood within the system ( 10 ), preferably in the range from 39 ° C to 44 ° C, preferably in the range from 40 ° C to 44 ° C, more preferably in the range from 40 ° C to 42.5 ° C, and / or
• - an input functionality for setting a target temperature ( TT1 ) of the body, preferably in the range from 38 ° C to 44 ° C, preferably in the range from 40 ° C to 44 ° C, more preferably in the range from 40 ° C to 42.5 ° C, and / or
• - an input functionality for setting a target flow rate ( TFR ) of the blood, preferably in the range from 1 liter per minute to 5 liters per minute, preferably in the range from 2 liters per minute to 4 liters per minute, more preferably in the range from 1.5 liters per minute to 3 liters per minute, and / or
• - an input functionality for setting a target time ( Tt1 ) for the operation of the system ( 10 ), preferably within a range from 1 hour to 8 hours, preferably within the range from 2 hours to 6 hours, more preferably within the range from 3 hours to 5 hours.

The input functionalities can be implemented by separate input elements or by a digital user interface, for example a touchscreen. The input functionalities can be implemented with the control unit mentioned above. This would enable the system to operate automatically.

The inner diameter of the tubes of the tube system can be in the range of 5 to 10 millimeters or 15 French to 30 French. This enables the high flow rates.

The system may include monitoring functionality that is configured to sense or measure the temperature of the blood within the system and / or that is configured to measure the body temperature of the subject, i. a person or an animal, records or measures. The control unit can control the system as a function of the temperature of the blood that is recorded or measured in the system. Alternatively or additionally, the control system can control the system as a function of the body temperature. It may be possible to set a value of the blood temperature within the system to a first target value within the system or to set a body temperature to a second target value. The setting can be made automatically or manually. Alternatively, it may be possible to keep one or both of these temperatures within a range defined by a lower and an upper value.

• - mindestens 50 Prozent, mindestens 75 Prozent oder mindestens 90 Prozent der Länge der Schläuche des Schlauchsystems sind thermisch isoliert,
• - die Steuervorrichtung ist konfiguriert, um die Temperatur des Blutes innerhalb des Schlauchsystems zu steuern, vorzugsweise unter Verwendung einer geschlossenen Regelkreis-Regelvorrichtung, vorzugsweise einer geschlossenen Regelkreis-Regelung, die ein Überschreiten der Temperatur über einen Zieltemperaturwert des Blutes und/oder einen Zieltemperaturwert des Körpers der Person verhindert,
• - die Steuervorrichtung ist konfiguriert, um die Temperatur des Körpers zu steuern, vorzugsweise unter Verwendung einer geschlossenen Regelkreis-Regelvorrichtung, vorzugsweise einer geschlossenen Regelkreis-Regelung, die ein Überschreiten der Temperatur über einen Zieltemperaturwert des Blutes und/oder einen Zieltemperaturwert des Körpers verhindert.

The system can include at least one, any combination, or all of the following features:

• - at least 50 percent, at least 75 percent or at least 90 percent of the length of the hoses in the hose system are thermally insulated,
• The control device is configured to control the temperature of the blood within the tube system, preferably using a closed-loop control device, preferably a closed-loop control, which allows the temperature to exceed a target temperature value of the blood and / or a target temperature value of the body prevents the person
• the control device is configured to control the temperature of the body, preferably using a closed-loop control device, preferably a closed-loop control, which prevents the temperature from exceeding a target temperature value of the blood and / or a target temperature value of the body.

Preventing the temperature from being exceeded can mean that an asymptotic course of the temperature is reached, i.e. it must be ensured that the target value is not exceeded. This can be important to the person's health.

The thermal insulation can e.g. done with a foam. The thermal insulation can take place for each hose individually, for groups of hoses or for parts of the hose system, e.g. using an insulated housing. The sheath can be transparent to allow a quick check that all tubes are properly connected. There may be insulation against thermal radiation and / or thermal conduction and / or thermal convection. Alternatively, heated hoses can be used, e.g. Hoses that are heated by electrical energy or by an additional liquid.

The system can include at least one connector that is configured to receive a chemical or biochemical substance that is added to the blood in the tubing system, preferably a substance that is used for chemotherapy. Thus a fourfold combination of treatment methods is possible with the system, i. Warming the blood, enriching the oxygen in the blood, filtering the blood and adding drugs to the blood. One type of medication can be blood thinning substances that prevent agglutination when the blood is heated. The connection can thus be an inlet connection for injections.

The inventor also provides extracorporeal blood above normal body temperature for use in the treatment of a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.

Thus, in a second aspect, the present invention relates to extracorporeal / isolated blood above normal body temperature for use in the treatment of a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis. Alternatively, extracorporeal / isolated blood can be above normal Body temperature can be used to treat a condition associated with high cholesterol.

In particular, a patient who has a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis is treated with extracorporeal / isolated blood above normal body temperature.

In one embodiment, the extracorporeal / isolated blood comes from a patient who has a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis. The blood has been collected / isolated from this patient and then heated above the patient's normal body temperature. Thereafter, the same patient is treated with this blood heated above normal body temperature.

In another alternative embodiment, the extracorporeal / isolated blood comes from another person, a blood donor. The blood has been obtained / isolated from this donor and then heated above the normal body temperature of the donor. The patient is then treated with the donor's blood, which is heated above normal body temperature. The donor does not have any disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and a sepsis. It should be noted that the normal body temperature of the donor is preferably comparable to or higher than the normal body temperature of the patient. In a particular embodiment, the donor's blood is heated above the patient's normal body temperature.

The normal body temperature refers to the typical temperature found in a person. The normal human body temperature range is e.g. typically given as 36.1 ° C to 37.5 ° C, e.g. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3 , 37.4 or 37.5 ° C.

It is preferred that the extracorporeal blood has a temperature between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C and more preferably between 40 ° C and 42.5 ° C, e.g. between 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5 or 44 ° C.

It is also preferred that the extracorporeal blood be oxygen-rich blood. Preferably the extracorporeal blood has been oxygenated by external means, e.g. with an oxygenator. The oxygenator increases the oxygen in the blood. With the extracorporeal blood enriched with oxygen, an oxygen saturation of the tissue of at least 400%, 500%, 600% or 700%, preferably of at least 700%, can generally be achieved.

It is further preferred that the blood is purified blood. Extracorporeal blood purification (EBP) is a treatment in which the blood of a patient / donor is passed through a device (e.g. membrane, sorbent) in which dissolved substances (e.g. waste products, toxins) and possibly also water are removed. When fluid is removed, replacement fluid is usually added. It is preferred that purified blood no longer comprises inflammatory, toxic molecules and / or other harmful molecules or comprises a smaller amount of these molecules in comparison with unpurified blood. Extracorporeal therapies that are used to remove or filter substances from the circulation in order to purify the blood include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies, and combinations of all of the above. Preferably the purified blood is filtered blood. Preferably the purified blood is dialyzed blood. Blood dialysis removes waste, salt, toxins, and extra water to keep them from building up in the body, maintains certain levels of certain chemicals in the blood like potassium, sodium, and bicarbonate, and helps control blood pressure. It is particularly preferred that the blood, e.g. the purified, filtered or dialyzed blood is free of inflammatory or other harmful molecules.

1. (i) ist der Krebs aus der Gruppe bestehend aus Hautkrebs, Nasen-Rachen-Krebs, neuroendrokrinem Krebs, Lungenkrebs, Dickdarmkrebs, Urothelkrebs, Blasenkrebs, Leberkrebs, Eierstockkrebs, Magenkrebs, Speiseröhrenkrebs, Bauchspeicheldrüsenkrebs, Nierenkrebs, Magenkrebs, Speiseröhrenkrebs, Brustkrebs, Nierenkrebs, Kopf- und Halskrebs, Hirnkrebs, Lymphdrüsenkrebs, Blutkrebs, Plattenepithelkrebs, Kehlkopfkrebs, Netzhautkrebs, Prostatakrebs, Gebärmutterhalskrebs, Gebärmutterkrebs, Hodenkrebs, Knochenkrebs, Lymphom und Leukämie ausgewählt,
2. (ii) ist die Autoimmunkrankheit aus der Gruppe bestehend aus Rheuma/rheumatischer Erkrankung, z.B. rheumatoider Arthritis (RA), Multiple Sklerose (MS), systemischer Lupus erythematodes (Lupus), Morbus Basedow, Sjögren-Syndrom, Hashimoto-Thyreoiditis, Myasthenia gravis, Vaskulitis, perniziöse Anämie und Zöliakie ausgewählt,
3. (iii) ist die Infektionskrankheit aus der Gruppe bestehend aus viraler Infektion, vorzugsweise chronischer oder persistierender viraler Infektion, bakterieller Infektion, parasitärer Infektion ausgewählt, oder
4. (iv) ist die entzündliche Erkrankung aus der Gruppe bestehend aus Atherosklerose, einer Autoimmunerkrankung, Allergie, Asthma, Zöliakie, Glomerulonephritis, Hepatitis und einer entzündlichen Darmerkrankung ausgewählt.

Preferably,

1. (i) the cancer is selected from the group consisting of skin cancer, nasopharyngeal cancer, neuroendrocal cancer, lung cancer, colon cancer, urothelial cancer, bladder cancer, liver cancer, ovarian cancer, stomach cancer, esophageal cancer, pancreatic cancer, kidney cancer, stomach cancer, esophageal cancer Head and neck cancer, brain cancer, lymph gland cancer, blood cancer, squamous cell cancer, larynx cancer, retinal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bone cancer, lymphoma and leukemia selected,
2. (ii) the autoimmune disease from the group consisting of rheumatism / rheumatic disease, e.g. rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (lupus), Graves' disease, Sjogren's syndrome, Hashimoto's thyroiditis, myasthenia gravis, Vasculitis, pernicious anemia and celiac disease selected,
3. (iii) the infectious disease is selected from the group consisting of viral infection, preferably chronic or persistent viral infection, bacterial infection, parasitic infection, or
4. (iv) the inflammatory disease is selected from the group consisting of atherosclerosis, an autoimmune disease, allergy, asthma, celiac disease, glomerulonephritis, hepatitis, and an inflammatory bowel disease.

1. (i) ist die Virusinfektion aus der Gruppe bestehend aus der Infektion mit dem humanen Immunschwächevirus (HIV), dem Hepatitis-B-Virus (HBV), dem Hepatitis-C-Virus (HCV), dem Rhinovirus (Schnupfen), dem Herpes-Simplex-Virus (HSV) und dem Respiratory-Syncytial-Virus (RSV) ausgewählt,
2. (ii) ist die bakterielle Infektion aus der Gruppe bestehend aus einer Infektion mit Borrelia burgdorferi (Borreliose), Helicobacter pylori, Mycobacterium tuberculosis, Mycobacterium leprae und Chlamydia trachomatis ausgewählt, oder
3. (iii) ist die parasitäre Infektion aus der Gruppe bestehend aus einer Infektion mit Schistosoma mansoni, Taenia crassiceps oder Leishmania mexicana ausgewählt.

Preferred,

1. (i) the virus infection from the group consisting of infection with the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV), the rhinovirus (runny nose), the herpes Simplex virus (HSV) and respiratory syncytial virus (RSV) selected,
2. (ii) the bacterial infection is selected from the group consisting of an infection with Borrelia burgdorferi (borreliosis), Helicobacter pylori, Mycobacterium tuberculosis, Mycobacterium leprae and Chlamydia trachomatis, or
3. (iii) the parasitic infection is selected from the group consisting of an infection with Schistosoma mansoni, Taenia crassiceps or Leishmania mexicana.

Preferred,
rheumatism / rheumatic disease caused by autoimmunity is selected from the group consisting of ankylosing spondylitis, recurrent polychondritis, lupus erythematosus, rheumatoid arthritis (RA), gout, inflammatory arthritis, pseudogout, juvenile arthritis, Sjogren's syndrome, scleroderma, Polymyositis, dermatomyositis, Behcet's disease, and psoriatic arthritis.

In a third aspect, the present invention relates to a combination of extracorporeal blood above normal body temperature and a chemotherapeutic agent for use in the treatment of cancer.

In particular, a patient suffering from cancer is treated with extracorporeal / isolated blood above normal body temperature.

In one embodiment, the extracorporeal / isolated blood comes from a patient suffering from cancer. The blood has been collected / isolated from this patient and then heated above the patient's normal body temperature. Thereafter, the same patient is treated with this blood heated above normal body temperature.

In another alternative embodiment, the extracorporeal / isolated blood comes from another subject, a blood donor. The blood has been obtained / isolated from this donor and then heated above the normal body temperature of the donor. The patient is then treated with the donor's blood, which is heated above normal body temperature. The donor does not have cancer.
It should be noted that the normal body temperature of the donor is preferably comparable to or higher than the normal body temperature of the patient. In a particular embodiment, the donor's blood is heated above the patient's normal body temperature.

The normal body temperature refers to the typical temperature found in a person. The normal human body temperature range is e.g. typically given as 36.1 ° C to 37.5 ° C, e.g. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3 , 37.4 or 37.5 ° C.

It is preferred that the extracorporeal blood has a temperature between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C and more preferably between 40 ° C and 42.5 ° C, e.g. between 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5 or 44 ° C.

It is also preferred that the extracorporeal blood be oxygen-rich blood. Preferably the extracorporeal blood has been oxygenated by external means, e.g. with an oxygenator. The oxygenator increases the oxygen in the blood.

It is further preferred that the blood is purified blood. Extracorporeal blood purification (EBP) is a treatment in which the blood of a patient / donor is passed through a device (e.g. membrane, sorbent) in which dissolved substances (e.g. waste products, toxins) and possibly also water are removed. When fluid is removed, replacement fluid is usually added. It is preferred that purified blood no longer comprises inflammatory, toxic molecules and / or other harmful molecules or comprises a smaller amount of these molecules in comparison with unpurified blood. Extracorporeal therapies that are used to remove or filter substances from the circulation in order to purify the blood include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies, and combinations of all of the above. Preferably the purified blood is filtered blood. Preferably the purified blood is dialyzed blood. Blood dialysis removes waste, salt, toxins, and extra water to keep them from building up in the body, maintains certain levels of certain chemicals in the blood like potassium, sodium, and bicarbonate, and helps control blood pressure. It is particularly preferred that the blood, for example the purified, filtered or dialyzed blood, is free of inflammatory or other harmful molecules.

It is further preferred that the cancer from the group consisting of skin cancer, nasopharyngeal cancer, neuroendrocrine cancer, lung cancer, colon cancer, urothelial cancer, bladder cancer, liver cancer, ovarian cancer, stomach cancer, esophageal cancer, pancreatic cancer, kidney cancer, breast cancer, esophagus cancer, Kidney cancer, head and neck cancer, brain cancer, lymph gland cancer, blood cancer, squamous cell cancer, throat cancer, retinal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bone cancer, lymphoma and leukemia is selected.

It is further preferred that the chemotherapeutic agent is selected from the group consisting of alkylating agents, anthracyclines, cytoskeletal disruptors, epothilones, histone deacetylase inhibitors, and topoisomerase inhibitors I. , Topoisomerase II inhibitors, kinase inhibitors, nucleotide analogs and precursor analogs, peptide antibiotics, platinum-based agents, and retinoids.
The chemotherapeutic agent is preferably suitable for being administered in such a way that it spreads widely in the patient's body in significant amounts and develops a biological effect (systemic administration). Typical systemic routes of administration are administration by introducing the chemotherapeutic agent directly into the vasculature, or oral, pulmonary or intramuscular administration, the chemotherapeutic agent entering the vasculature and being transported via the blood to one or more desired sites of action (s). Systemic administration can be by parenteral administration.
Alternatively, the chemotherapeutic agent is suitable to be administered in such a way that it does not pass through the intestine (parenteral administration). Parenteral administration includes, but is not limited to, intravenous administration, subcutaneous administration, intradermal administration, or intra-arterial administration.
In particular, the chemotherapeutic agent is suitable, topical, intravenous, intradermal, intraarterial, intraperitoneal, intralesional, intracranial, intraarticular, intraprostatic, intrapleural, intratracheal, intraocular, intranasal, intravitreal, intravaginal, intrarectal, intramuscular, intraperitoneal, subcutaneous, subconjunctival To be administered intraumbilical, orally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion of swimming target cells directly, via a catheter or via a lavage.
The dose that can be administered to a patient (“a therapeutically effective amount” or simply “an effective amount”) should be sufficient to produce a beneficial therapeutic response in the patient over time. The dose is determined by the effectiveness of the chemotherapeutic agent used and the condition of the patient as well as the body weight of the patient to be treated or the size of the surface to be treated. The size of the dose will also be determined by the presence, nature, and extent of undesirable side effects associated with administration of the chemotherapeutic agent in a particular patient.
The chemotherapeutic agent is suitable in an amount of 0.1 to 10 mg / kg of body weight, preferably 0.2 to 8 mg / kg of body weight, more preferably 0.3 to 6 mg / kg of body weight, more preferably 0.4 to 5 mg / kg Body weight, more preferably 0.5 to 4 mg / kg body weight to be administered.

• Verabreichen von extrakorporalem Blut oberhalb der normalen Körpertemperatur an einen Patienten, der dieses benötigt,
• wobei die Erkrankung aus der Gruppe bestehend aus Krebs, einer Autoimmunerkrankung, einer Infektionserkrankung, einer entzündlichen Erkrankung und Sepsis ausgewählt ist.
• Alternativ kann extrakorporales Blut oberhalb der normalen Körpertemperatur verabreicht werden, um eine Krankheit zu behandeln, die mit erhöhten Cholesterinwerten einhergeht.

In a fourth aspect, the present invention relates to a method for treating a disease in a patient, comprising the step:

• Administering extracorporeal blood above normal body temperature to a patient in need of it,
• wherein the disease is selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.
• Alternatively, extracorporeal blood above normal body temperature can be administered to treat a disease associated with elevated cholesterol levels.

In particular, the patient suffers from a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.

In one embodiment, the extracorporeal blood comes from a patient suffering from a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis. The blood is collected / isolated from this patient and then heated above the patient's normal body temperature. Thereafter, the blood heated above the patient's normal body temperature is administered to the same patient.

In another alternative embodiment, the extracorporeal / isolated blood comes from another person, a blood donor. The blood is collected / isolated from this donor and then heated above the donor's normal body temperature. Thereafter, the blood, heated above the normal body temperature of the donor, is administered to the patient. The donor does not have a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease, and sepsis. It should be noted that the normal body temperature of the donor is preferably comparable to or higher than the normal body temperature of the patient. In a particular embodiment, the donor's blood is heated above the patient's normal body temperature.

The normal body temperature refers to the typical temperature found in a person. The normal human body temperature range is e.g. typically given as 36.1 ° C to 37.5 ° C, e.g. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3 , 37.4 or 37.5 ° C.

It is preferred that the extracorporeal blood has a temperature between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C and more preferably between 40 ° C and 42.5 ° C, e.g. between 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5 or 44 ° C.

It is also preferred that the extracorporeal blood be oxygenated prior to administration. The oxygenation of the extracorporeal blood is preferably carried out by external means, e.g. by an oxygenator. The oxygenator increases the oxygen in the blood.

It is also preferred that the blood be purified prior to administration. Extracorporeal blood purification (EBP) is a treatment in which the blood of a patient / donor is passed through a device (e.g. membrane, sorbent) in which dissolved substances (e.g. waste products, toxins) and possibly also water are removed. When fluid is removed, replacement fluid is usually added. It is preferred that purified blood no longer comprises inflammatory, toxic molecules and / or other harmful molecules or comprises a smaller amount of these molecules in comparison with unpurified blood. Extracorporeal therapies that are used to remove or filter substances from the circulation in order to purify blood include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies and combinations of the above methods. Preferably the purified blood is filtered blood. Preferably the purified blood is dialyzed blood. Blood dialysis removes waste, salt, toxins, and extra water to keep them from building up in the body, maintains certain levels of certain chemicals in the blood like potassium, sodium, and bicarbonate, and helps control blood pressure. It is particularly preferred that the blood, e.g. the purified, filtered or dialyzed blood is free of inflammatory or other harmful molecules.

The technique of warming / heating extracorporeal blood above normal body temperature is also known as hemo / hemohyperthermia. The technique of blood purification is also known as hemoperfusion / hemoperfusion. In combination with the oxygenation of the blood, this technique is also referred to as hyperoxygenated hemoperfusion / hemoperfusion. The combination of heating the extracorporeal blood above normal body temperature, filtering the extracorporeal blood and oxygenation of the extracorporeal blood is also referred to as extracorporeal hyperthermia perfusion therapy (EHP).

1. (i) ist der Krebs aus der Gruppe bestehend aus Hautkrebs, Nasen-Rachen-Krebs, neuroendrokrinem Krebs, Lungenkrebs, Dickdarmkrebs, Urothelkrebs, Blasenkrebs, Leberkrebs, Eierstockkrebs, Magenkrebs, Speiseröhrenkrebs, Bauchspeicheldrüsenkrebs, Nierenkrebs, Magenkrebs, Speiseröhrenkrebs, Brustkrebs, Nierenkrebs, Kopf- und Halskrebs, Hirnkrebs, Lymphdrüsenkrebs, Blutkrebs, Plattenepithelkrebs, Kehlkopfkrebs, Netzhautkrebs, Prostatakrebs, Gebärmutterhalskrebs, Gebärmutterkrebs, Hodenkrebs, Knochenkrebs, Lymphom und Leukämie ausgewählt,
2. (ii) ist die Autoimmunkrankheit aus der Gruppe bestehend aus Rheuma/rheumatischer Erkrankung, z.B. rheumatoider Arthritis (RA), Multiple Sklerose (MS), systemischer Lupus erythematodes (Lupus), Morbus Basedow, Sjögren-Syndrom, Hashimoto-Thyreoiditis, Myasthenia gravis, Vaskulitis, perniziöser Anämie und Zöliakie ausgewählt,
3. (iii) ist die Infektionskrankheit aus der Gruppe bestehend aus viraler Infektion, vorzugsweise chronischer oder persistierender viraler Infektion, bakterieller Infektion, parasitärer Infektion ausgewählt, oder
4. (iv) ist die entzündliche Erkrankung aus der Gruppe bestehend aus Atherosklerose, einer Autoimmunerkrankung, Allergie, Asthma, Zöliakie, Glomerulonephritis, Hepatitis und einer entzündlichen Darmerkrankung ausgewählt.

Preferably,

1. (i) the cancer is selected from the group consisting of skin cancer, nasopharyngeal cancer, neuroendrocal cancer, lung cancer, colon cancer, urothelial cancer, bladder cancer, liver cancer, ovarian cancer, stomach cancer, esophageal cancer, pancreatic cancer, kidney cancer, stomach cancer, esophageal cancer Head and neck cancer, brain cancer, lymph gland cancer, blood cancer, squamous cell cancer, larynx cancer, retinal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bone cancer, lymphoma and leukemia selected,
2. (ii) the autoimmune disease from the group consisting of rheumatism / rheumatic disease, e.g. rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (lupus), Graves' disease, Sjogren's syndrome, Hashimoto's thyroiditis, myasthenia gravis, Vasculitis, pernicious anemia and celiac disease selected,
3. (iii) the infectious disease is selected from the group consisting of viral infection, preferably chronic or persistent viral infection, bacterial infection, parasitic infection, or
4. (iv) the inflammatory disease is selected from the group consisting of atherosclerosis, an autoimmune disease, allergy, asthma, celiac disease, glomerulonephritis, hepatitis, and an inflammatory bowel disease.

1. (i) ist die Virusinfektion aus der Gruppe bestehend aus der Infektion mit dem humanen Immunschwächevirus (HIV), dem Hepatitis-B-Virus (HBV), dem Hepatitis-C-Virus (HCV), dem Rhinovirus (Schnupfen), dem Herpes-Simplex-Virus (HSV) und dem Respiratory-Syncytial-Virus (RSV) ausgewählt,
2. (ii) ist die bakterielle Infektion aus der Gruppe bestehend aus einer Infektion mit Borrelia burgdorferi (Borreliose), Helicobacter pylori, Mycobacterium tuberculosis, Mycobacterium leprae und Chlamydia trachomatis ausgewählt, oder
3. (iii) ist die parasitäre Infektion aus der Gruppe bestehend aus einer Infektion mit Schistosoma mansoni, Taenia crassiceps oder Leishmania mexicana ausgewählt.

Preferred,

1. (i) the virus infection from the group consisting of infection with the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV), the rhinovirus (runny nose), the herpes Simplex virus (HSV) and respiratory syncytial virus (RSV) selected,
2. (ii) the bacterial infection is selected from the group consisting of an infection with Borrelia burgdorferi (borreliosis), Helicobacter pylori, Mycobacterium tuberculosis, Mycobacterium leprae and Chlamydia trachomatis, or
3. (iii) the parasitic infection is selected from the group consisting of an infection with Schistosoma mansoni, Taenia crassiceps or Leishmania mexicana.

Preferred,
rheumatism / rheumatic disease caused by autoimmunity is selected from the group consisting of ankylosing spondylitis, recurrent polychondritis, lupus erythematosus, rheumatoid arthritis (RA), gout, inflammatory arthritis, pseudogout, juvenile arthritis, Sjogren's syndrome, scleroderma, Polymyositis, dermatomyositis, Behcet's disease, and psoriatic arthritis.

In a preferred embodiment, the disease is cancer and the method further comprises the step of administering a chemotherapeutic agent to the patient. The chemotherapeutic agent is preferably administered in such a way that the agent spreads widely in the patient's body in significant amounts and develops a biological effect (systemic administration). Typical systemic routes of administration are administration by introducing the chemotherapeutic agent directly into the vasculature, or oral, pulmonary or intramuscular administration, the chemotherapeutic agent entering the vasculature and being transported via the blood to one or more desired sites of action (s). Systemic administration can be by parenteral administration.
Alternatively, the chemotherapeutic agent is administered in such a way that the agent does not pass through the intestine (parenteral administration). Parenteral administration includes, but is not limited to, intravenous administration, subcutaneous administration, intradermal administration, or intra-arterial administration.
The dose (“a therapeutically effective amount” or simply “an effective amount”) administered to a patient should be sufficient to produce a beneficial therapeutic response in the patient over time. The dose is determined by the effectiveness of the chemotherapeutic agent used and the condition of the patient as well as by the body weight of the patient to be treated or the size of the surface to be treated. The size of the dose will also be determined by the presence, nature, and extent of undesirable side effects associated with administration of the chemotherapeutic agent in a particular patient.
The chemotherapeutic agent is preferably administered in an amount of 0.1 to 10 mg / kg body weight, preferably 0.2 to 8 mg / kg body weight, more preferably 0.3 to 6 mg / kg body weight, more preferably 0.4 to 5 mg / kg Body weight, more preferably 0.5 to 4 mg / kg body weight.
In one embodiment, the chemotherapeutic agent is administered to the patient before the administration of the extracorporeal blood above normal body temperature to the patient, for example within a week or 1, 2, 3, 4, 5, 6 or 7 day (s) before the administration of the extracorporeal blood Blood above normal body temperature to the patient.
In another alternative embodiment, the chemotherapeutic agent is administered to the patient after, in particular immediately after, the administration of the extracorporeal blood to the patient above normal body temperature, e.g. within a week or 1, 2, 3, 4, 5, 6 or 7 days ( e) after the administration of the extracorporeal blood to the patient above normal body temperature.
In another alternative embodiment, the chemotherapeutic agent is administered to the patient during the administration of the extracorporeal blood to the patient above normal body temperature or simultaneously with the administration of the extracorporeal blood to the patient above normal body temperature.
In particular, the chemotherapeutic agent can be given to the patient either during the administration of the extracorporeal blood to the patient above normal body temperature (e.g. simultaneously or almost simultaneously, e.g. during the period of blood administration) or separately (e.g. administration at different times Times that are typically more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 or more hours apart) are administered. For example, the chemotherapeutic agent can be administered up to 6 or 12 hours before or after the administration of the blood. In some cases, it is possible to give the chemotherapy agent to a patient by intravenous infusion. The patient can then be given the blood up to 6 or 12 hours later.

In another preferred embodiment, the disease is cancer and the method further comprises the step of performing radiation therapy on the patient or applying radiation therapy to the patient.
The amount of radiation used in photon radiation therapy is measured in gray levels (Gy) and varies depending on the type and stage of cancer being treated. In particular, the typical dose for a solid epithelial tumor is between 60 and 80 Gy, while lymphomas are treated with 20 to 40 Gy in curative cases.
Radiation therapy can be external radiation therapy (EBRT or XRT) or teletherapy, brachytherapy or radiation therapy with an enclosed source, or systemic radioisotope therapy or radiation therapy with an unclosed source.
Radiation therapy can be performed before (e.g. 1 week before or 1, 2, 3, 4, 5, 6 or 7 day (s) before) or after (e.g. 1 week after or 1, 2, 3, 4, 5, 6 or 7 Day (s) after) the administration of the extracorporeal blood above normal body temperature to the patient. Alternatively, the radiation therapy can be carried out simultaneously or almost simultaneously with the administration of the extracorporeal blood above normal body temperature to the patient.

Especially
the administration of the extracorporeal blood above normal body temperature, the administration of the chemotherapeutic agent and the application of radiation therapy can take place simultaneously or almost simultaneously,
the administration of the chemotherapeutic agent and the application of radiation therapy can take place before or after the administration of extracorporeal blood above normal body temperature,
the administration of the chemotherapeutic agent can take place before the administration of extracorporeal blood above normal body temperature and the radiation therapy can be applied after the administration of extracorporeal blood above normal body temperature, or
For example, the radiation therapy can be used before the administration of extracorporeal blood above normal body temperature and the chemotherapeutic agent can be used after the administration of extracorporeal blood above normal body temperature.

In addition to radiation therapy and / or chemotherapy (by administering a chemotherapeutic drug), cancer surgery can be performed to remove the cancer and nearby tissue and / or cancer metastases from the body in one surgery. Cancer surgery can also be used as an alternative to radiation therapy and / or chemotherapy. The cancer operation is preferably performed on a patient in need of extracorporeal blood which is above normal body temperature is administered. The cancer operation is preferably carried out before the administration of extracorporeal blood above normal body temperature and before radiation therapy and / or chemotherapy is carried out.

In a preferred embodiment, the patient who is administered extracorporeal blood above normal body temperature has already received a cancer operation and / or an operation for cancer metastases. This therapy was carried out before the heat treatment.

• Verabreichen von extrakorporalem Blut oberhalb der normalen Körpertemperatur in Kombination mit einem chemotherapeutischen Mittel an einen Patienten, der dieses benötigt.

In a fifth aspect, the present invention relates to a method for treating cancer, comprising the step:

• Administering extracorporeal blood above normal body temperature in combination with a chemotherapeutic agent to a patient in need thereof.

The patient particularly suffers from cancer.

In one embodiment, the extracorporeal blood comes from the patient suffering from cancer. The blood is collected / isolated from this patient and then heated above the patient's normal body temperature. Thereafter, the blood heated above the patient's normal body temperature is administered to the same patient.

In another alternative embodiment, the extracorporeal / isolated blood comes from another person, a blood donor. The blood is collected / isolated from this donor and then heated above the donor's normal body temperature. Thereafter, the blood, heated above the normal body temperature of the donor, is administered to the patient. The donor does not have cancer. It should be noted that the normal body temperature of the donor is preferably comparable to or higher than the normal body temperature of the patient. In a particular embodiment, the donor's blood is heated above the patient's normal body temperature.

The normal body temperature refers to the typical temperature found in a person. The normal human body temperature range is e.g. typically given as 36.1 ° C to 37.5 ° C, e.g. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3 , 37.4 or 37.5 ° C.

It is preferred that the extracorporeal blood has a temperature between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C and more preferably between 40 ° C and 42.5 ° C, e.g. between 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5 or 44 ° C.

It is also preferred that the extracorporeal blood be oxygenated prior to administration. The oxygenation of the extracorporeal blood is preferably carried out by external means, e.g. by an oxygenator. The oxygenator increases the oxygen in the blood.

It is also preferred that the blood is purified before administration. Extracorporeal blood purification (EBP) is a treatment in which the blood of a patient / donor is passed through a device (e.g. membrane, sorbent) in which dissolved substances (e.g. waste products, toxins) and possibly also water are removed. When fluid is removed, replacement fluid is usually added. It is preferred that purified blood no longer comprises inflammatory, toxic molecules and / or other harmful molecules or comprises a smaller amount of these molecules in comparison with unpurified blood. Extracorporeal therapies that are used to remove or filter substances from the circulation in order to purify blood include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies and combinations of the above methods. Preferably the purified blood is filtered blood. Preferably the purified blood is dialyzed blood. Blood dialysis removes waste, salt, toxins, and extra water to keep them from building up in the body, maintains certain levels of certain chemicals in the blood like potassium, sodium, and bicarbonate, and helps control blood pressure. It is particularly preferred that the blood, e.g. the purified, filtered or dialyzed blood is free of inflammatory or other harmful molecules.

The technique of warming / heating extracorporeal blood above normal body temperature is also known as hemo- / hemohyperthermia. The technique of blood purification is also known as hemoperfusion / hemoperfusion. In combination with the oxygenation of the blood, this technique is also referred to as hyperoxygenated hemoperfusion / hemoperfusion. The combination of heating the extracorporeal blood above normal body temperature, filtering the extracorporeal blood and oxygenating the extracorporeal blood is also referred to as extracorporeal hyperthermia perfusion therapy (EHP).

It is further preferred that the cancer is selected from the group consisting of skin cancer, nasopharyngeal cancer, neuroendrocrine cancer, lung cancer, colon cancer, urothelial cancer, bladder cancer, liver cancer, ovarian cancer, stomach cancer, esophageal cancer, pancreatic cancer, kidney cancer, breast cancer, esophagus cancer , Kidney cancer, head and neck cancer, brain cancer, lymph gland cancer, blood cancer, squamous cell cancer, larynx cancer, retinal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bone cancer, lymphoma and leukemia is selected.

The chemotherapeutic agent is preferably administered in such a way that the agent spreads widely in the patient's body in significant amounts and develops a biological effect (systemic administration). Typical systemic routes of administration are administration by introducing the chemotherapeutic agent directly into the vasculature, or oral, pulmonary or intramuscular administration, the chemotherapeutic agent entering the vasculature and being transported via the blood to one or more desired sites of action (s). Systemic administration can be by parenteral administration.
Alternatively, the chemotherapeutic agent is administered in such a way that the agent does not pass through the intestine (parenteral administration). Parenteral administration includes, but is not limited to, intravenous administration, subcutaneous administration, intradermal administration, or intra-arterial administration.
The chemotherapeutic agent is preferably administered in an amount of 0.1 to 10 mg / kg body weight, preferably 0.2 to 8 mg / kg body weight, more preferably 0.3 to 6 mg / kg body weight, more preferably 0.4 to 5 mg / kg Body weight, more preferably 0.5 to 4 mg / kg body weight.
In one embodiment, the chemotherapeutic agent is administered to the patient before the administration of the extracorporeal blood above normal body temperature to the patient, for example within a week or 1, 2, 3, 4, 5, 6 or 7 day (s) before the administration of the extracorporeal blood Blood above normal body temperature to the patient.
In another alternative embodiment, the chemotherapeutic agent is administered to the patient after, in particular immediately after, the administration of the extracorporeal blood to the patient above normal body temperature, e.g. within a week or 1, 2, 3, 4, 5, 6 or 7 days ( e) after the administration of the extracorporeal blood to the patient above normal body temperature.
In another alternative embodiment, the chemotherapeutic agent is administered to the patient during the administration of the extracorporeal blood to the patient above normal body temperature or simultaneously with the administration of the extracorporeal blood to the patient above normal body temperature.
In particular, the chemotherapeutic agent can be given to the patient either during the administration of the extracorporeal blood to the patient above normal body temperature (e.g. simultaneously or almost simultaneously, e.g. during the period of blood administration) or separately (e.g. administration at different times Times that are typically more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 or more hours apart) are administered. For example, the chemotherapeutic agent can be administered up to 6 or 12 hours before or after the administration of the blood. In some cases, it is possible to give the chemotherapy agent to a patient by intravenous infusion. The patient can then be given the blood up to 6 or 12 hours later.

In a preferred embodiment, the method further comprises the step of performing radiation therapy on the patient or applying radiation therapy to the patient.
The amount of radiation used in photon radiation therapy is measured in gray levels (Gy) and varies depending on the type and stage of cancer being treated. In particular, the typical dose for a solid epithelial tumor is between 60 and 80 Gy, while lymphomas are treated with 20 to 40 Gy in curative cases.
Radiation therapy can be external radiation therapy (EBRT or XRT) or teletherapy, brachytherapy or radiation therapy with an enclosed source, or systemic radioisotope therapy or radiation therapy with an unclosed source.
Radiation therapy can be performed before (e.g. 1 week before or 1, 2, 3, 4, 5, 6 or 7 day (s) before) or after (e.g. 1 week after or 1, 2, 3, 4, 5, 6 or 7 Day (s) after) the administration of the extracorporeal blood above normal body temperature to the patient. Alternatively, the radiation therapy can be carried out simultaneously or almost simultaneously with the administration of the extracorporeal blood above normal body temperature to the patient.

Especially
the administration of the extracorporeal blood above normal body temperature, the administration of the chemotherapeutic agent and the application of radiation therapy can take place simultaneously or almost simultaneously,
the administration of the chemotherapeutic agent and the application of radiation therapy can take place before or after the administration of extracorporeal blood above normal body temperature,
the administration of the chemotherapeutic agent can take place before the administration of extracorporeal blood above normal body temperature and the radiation therapy can be applied after the administration of extracorporeal blood above normal body temperature, or
For example, the radiation therapy can be used before the administration of extracorporeal blood above normal body temperature and the chemotherapeutic agent can be used after the administration of extracorporeal blood above normal body temperature.

In addition to radiation therapy and / or chemotherapy (by administering a chemotherapeutic agent), cancer surgery can be performed to remove the cancer and nearby tissue and / or cancer metastases from the body in one surgery. Cancer surgery can also be used as an alternative to radiation therapy and / or chemotherapy. The cancer operation is preferably performed on a patient in need of extracorporeal blood which is above normal body temperature is administered. The cancer operation is preferably carried out before the administration of extracorporeal blood above normal body temperature and before radiation therapy and / or chemotherapy is carried out.

In a preferred embodiment, the patient who is administered extracorporeal blood above normal body temperature has already received a cancer operation and / or an operation for cancer metastases. This therapy was carried out before the heat treatment.

• Verabreichen von extrakorporalem Blut oberhalb der normalen Körpertemperatur an einen Patienten, der dieses benötigt, und Durchführen einer Strahlentherapie.

In a sixth aspect, the present invention relates to a method for treating cancer in a patient, comprising the following step:

• Administering extracorporeal blood above normal body temperature to a patient in need of it and performing radiation therapy.

The patient particularly suffers from cancer.

In one embodiment, the extracorporeal blood comes from the patient suffering from cancer. The blood is collected / isolated from this patient and then heated above the patient's normal body temperature. Thereafter, the blood heated above the patient's normal body temperature is administered to the same patient.

In another alternative embodiment, the extracorporeal / isolated blood comes from another person, a blood donor. The blood is collected / isolated from this donor and then heated above the donor's normal body temperature. Thereafter, the blood, heated above the normal body temperature of the donor, is administered to the patient. The donor does not have cancer. It should be noted that the normal body temperature of the donor is preferably comparable to or higher than the normal body temperature of the patient. In a particular embodiment, the donor's blood is heated above the patient's normal body temperature.

Normal body temperature refers to the typical temperature found in a person. The normal human body temperature range is e.g. typically given as 36.1 ° C to 37.5 ° C, e.g. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3 , 37.4 or 37.5 ° C.

It is preferred that the extracorporeal blood has a temperature between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C and more preferably between 40 ° C and 42.5 ° C, e.g. between 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5 or 44 ° C.

It is also preferred that the extracorporeal blood be oxygenated prior to administration. The oxygenation of the extracorporeal blood is preferably carried out by external means, e.g. by an oxygenator. The oxygenator increases the oxygen in the blood.

It is also preferred that the blood is purified before administration. Extracorporeal blood purification (EBP) is a treatment in which the blood of a patient / donor is passed through a device (e.g. membrane, sorbent) in which dissolved substances (e.g. waste products, toxins) and possibly also water are removed. When fluid is removed, replacement fluid is usually added. It is preferred that purified blood does not contain inflammatory, toxic molecules and / or others contains more harmful molecules or contains a smaller amount of these molecules compared to unpurified blood. Extracorporeal therapies that are used to remove or filter substances from the circulation in order to purify blood include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies and combinations of the above methods. Preferably the purified blood is filtered blood. Preferably the purified blood is dialyzed blood. Blood dialysis removes waste, salt, toxins, and extra water to keep them from building up in the body, maintains certain levels of certain chemicals in the blood like potassium, sodium, and bicarbonate, and helps control blood pressure. It is particularly preferred that the blood, for example the purified, filtered or dialyzed blood, is free of inflammatory or other harmful molecules.

The technique of warming / heating extracorporeal blood above normal body temperature is also known as hemo / hemohyperthermia. The technique of blood purification is also known as hemoperfusion / hemoperfusion. In combination with the oxygenation of the blood, this technique is also referred to as hyperoxygenated hemoperfusion / hemoperfusion. The combination of heating the extracorporeal blood above normal body temperature, filtering the extracorporeal blood and oxygenating the extracorporeal blood is also referred to as extracorporeal hyperthermia perfusion therapy (EHP).

It is further preferred that the cancer from the group consisting of skin cancer, nasopharyngeal cancer, neuroendrocrine cancer, lung cancer, colon cancer, urothelial cancer, bladder cancer, liver cancer, ovarian cancer, stomach cancer, esophageal cancer, pancreatic cancer, kidney cancer, breast cancer, esophagus cancer, Kidney cancer, head and neck cancer, brain cancer, lymph gland cancer, blood cancer, squamous cell cancer, throat cancer, retinal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bone cancer, lymphoma and leukemia is selected.

The amount of radiation used in photon radiation therapy is measured in gray levels (Gy) and varies depending on the type and stage of cancer being treated. In particular, the typical dose for a solid epithelial tumor is between 60 and 80 Gy, while lymphomas are treated with 20 to 40 Gy in curative cases.
Radiation therapy can be external radiation therapy (EBRT or XRT) or teletherapy, brachytherapy or radiation therapy with an enclosed source, or systemic radioisotope therapy or radiation therapy with an unclosed source.
Radiation therapy can be performed before (e.g. 1 week before or 1, 2, 3, 4, 5, 6 or 7 day (s) before) or after (e.g. 1 week after or 1, 2, 3, 4, 5, 6 or 7 Day (s) after) the administration of the extracorporeal blood above normal body temperature to the patient. Alternatively, the radiation therapy can be carried out simultaneously or almost simultaneously with the administration of the extracorporeal blood above normal body temperature to the patient.

In a preferred embodiment, the method further comprises the step of administering a chemotherapeutic agent to the patient.
The chemotherapeutic agent is preferably administered in such a way that the agent spreads widely in the patient's body in significant amounts and develops a biological effect (systemic administration). Typical systemic routes of administration are administration by introducing the chemotherapeutic agent directly into the vasculature, or oral, pulmonary or intramuscular administration, the chemotherapeutic agent entering the vasculature and being transported via the blood to one or more desired sites of action (s). Systemic administration can be by parenteral administration.
Alternatively, the chemotherapeutic agent is administered in such a way that the agent does not pass through the intestine (parenteral administration). Parenteral administration includes, but is not limited to, intravenous administration, subcutaneous administration, intradermal administration, or intra-arterial administration.
The chemotherapeutic agent is preferably administered in an amount of 0.1 to 10 mg / kg body weight, preferably 0.2 to 8 mg / kg body weight, more preferably 0.3 to 6 mg / kg body weight, more preferably 0.4 to 5 mg / kg Body weight, more preferably 0.5 to 4 mg / kg body weight.
In one embodiment, the chemotherapeutic agent is administered to the patient before the administration of the extracorporeal blood above normal body temperature to the patient, for example within a week or 1, 2, 3, 4, 5, 6 or 7 day (s) before the administration of the extracorporeal blood Blood above normal body temperature to the patient.
In another alternative embodiment, the chemotherapeutic agent is administered to the patient after, in particular immediately after, the administration of the extracorporeal blood to the patient above normal body temperature, e.g. within a week or 1, 2, 3, 4, 5, 6 or 7 days ( e) after the administration of the extracorporeal blood to the patient above normal body temperature.
In another alternative embodiment, the chemotherapeutic agent is administered to the patient during the administration of the extracorporeal blood to the patient above normal body temperature or simultaneously with the administration of the extracorporeal blood to the patient above normal body temperature.

In particular, the chemotherapeutic agent can be given to the patient either during the administration of the extracorporeal blood above normal body temperature to the patient (e.g. simultaneously or almost simultaneously, e.g. during the period of blood administration) or separately (e.g. administration at different times, typically more than 2, 3 , 4, 5, 6, 7, 8, 9, 10, 12 or more hours apart). For example, the chemotherapeutic agent can be administered up to 6 or 12 hours before or after the administration of the blood. In some cases, it is possible to give the chemotherapy agent to a patient by intravenous infusion. The patient can then be given the blood up to 6 or 12 hours later.

Especially
the administration of the extracorporeal blood above normal body temperature, the administration of the chemotherapeutic agent and the application of radiation therapy can take place simultaneously or almost simultaneously,
the administration of the chemotherapeutic agent and the application of radiation therapy can take place before or after the administration of extracorporeal blood above normal body temperature,
the administration of the chemotherapeutic agent can take place before the administration of extracorporeal blood above normal body temperature and the radiation therapy can be applied after the administration of extracorporeal blood above normal body temperature, or
For example, the radiation therapy can be used before the administration of extracorporeal blood above normal body temperature and the chemotherapeutic agent can be used after the administration of extracorporeal blood above normal body temperature.

In addition to radiation therapy and / or chemotherapy (by administering a chemotherapeutic drug), cancer surgery can be performed to remove the cancer and nearby tissue and / or cancer metastases from the body in one surgery. Cancer surgery can also be used as an alternative to radiation therapy and / or chemotherapy. The cancer operation is preferably carried out on a patient who needs this before the administration of extracorporeal blood which is above normal body temperature. The cancer operation is preferably carried out before the administration of extracorporeal blood above normal body temperature and before radiation therapy and / or chemotherapy is carried out.

In a preferred embodiment, the patient who is administered extracorporeal blood above normal body temperature has already received a cancer operation and / or an operation for cancer metastases. This therapy was carried out before the heat treatment.

1. (i) Erhitzen von extrakorporalem Blut, das aus dem Blutkreislauf des Patienten gewonnen wurde, oberhalb der Körpertemperatur, und
2. (ii) Rückführen des erhitzten Bluts in den Blutkreislauf des Patienten,

wobei die Erkrankung aus der Gruppe bestehend aus Krebs, einer Autoimmunerkrankung, einer Infektionserkrankung, einer entzündlichen Erkrankung und Sepsis ausgewählt ist.In a seventh aspect, the present invention relates to a method for treating a disease in a patient, comprising the steps:

1. (i) heating extracorporeal blood obtained from the patient's circulatory system above body temperature, and
2. (ii) returning the heated blood to the patient's bloodstream,

wherein the disease is selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.

The blood is preferably obtained from the patient's bloodstream before it is heated.

In particular, the patient suffers from a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.

In particular, the extracorporeal blood comes from a patient suffering from a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis.

It is preferred that the extracorporeal blood obtained from the patient's blood circulation has a temperature between 36.1 ° C. and 37.5 ° C., for example 36.1, 36.2, 36.3, 36.4, 36.5 , 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3, 37.4 or 37.5 ° C.

It is further preferred that the extracorporeal blood is heated to a temperature between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C, and more preferably between 40 ° C and 42.5 ° C, e.g. between 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5 or 44 ° C.

The extracorporeal blood is preferably heated with a heat transfer device. The heat transfer device preferably consists of a heat exchanger or an electric heater. The heat transfer device is preferably a device as described in connection with the first aspect of the present invention. This heat transfer device preferably functions as described in connection with the first aspect of the present invention.

The extracorporeal blood is preferably enriched with oxygen during the warming up, parallel to the warming up, or after the warming up and before the warming-up blood is returned to the patient's bloodstream. The extracorporeal blood is preferably enriched with oxygen by external means, for example by an oxygenator. The oxygenator increases the oxygen in the blood.
The oxygenator is preferably a device as described in connection with the first aspect of the present invention. This oxygenator preferably functions as described in connection with the first aspect of the present invention.

During the heating, parallel to the heating, or after the heating and before the return of the heated blood into the bloodstream of the patient, the blood is preferably cleaned. The extracorporeal blood purification (EBP) is a treatment in which the blood of a patient / donor is passed through a device (e.g. membrane, sorbent) in which dissolved substances (e.g. waste products, toxins) and possibly also water are removed. When fluid is removed, replacement fluid is usually added. It is preferred that the purified blood no longer comprises inflammatory, toxic molecules and / or other harmful molecules or comprises a smaller amount of these molecules compared to unpurified blood. Extracorporeal therapies that are used to remove or filter substances from the circulation in order to purify the blood include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies and combinations of the above methods. Preferably the purified blood is filtered blood. More preferably, the purified blood is dialyzed blood. Blood dialysis removes waste, salt, toxins, and extra water to keep them from building up in the body, maintains certain levels of certain chemicals in the blood like potassium, sodium, and bicarbonate, and helps control blood pressure. It is particularly preferred that the blood, for example the purified, filtered or dialyzed blood, is free of inflammatory or other harmful molecules.
The adsorber, in particular the filter, is preferably a device as described in connection with the first aspect of the present invention. The adsorber, in particular the filter, preferably functions as it is described in connection with the first aspect of the present invention.

Therefore, it is preferable that the blood be purified / filtered / dialyzed during the heating process, in parallel with the heating process, or after the heating process and before returning the heated blood to the patient's bloodstream. Alternatively or in addition, it is further preferred that the blood be enriched with oxygen during the heating process, parallel to the heating process, or after the heating process and before the heated blood is returned to the patient's bloodstream.

The technique of warming / heating extracorporeal blood above normal body temperature is also known as hemo / hemo-hyperthermia. The technique of blood purification is also known as hemoperfusion / hemoperfusion. In combination with the oxygenation of the blood, this technique is also referred to as hyperoxygenated hemoperfusion / hemoperfusion. The combination of heating the extracorporeal blood above normal body temperature, filtering the extracorporeal blood and oxygenating the extracorporeal blood is also referred to as extracorporeal hyperthermia perfusion therapy (EHP).

1. (i) ist der Krebs aus der Gruppe bestehend aus Hautkrebs, Nasen-Rachen-Krebs, neuroendrokrinem Krebs, Lungenkrebs, Dickdarmkrebs, Urothelkrebs, Blasenkrebs, Leberkrebs, Eierstockkrebs, Magenkrebs, Speiseröhrenkrebs, Bauchspeicheldrüsenkrebs, Nierenkrebs, Magenkrebs, Speiseröhrenkrebs, Brustkrebs, Nierenkrebs, Kopf- und Halskrebs, Hirnkrebs, Lymphdrüsenkrebs, Blutkrebs, Plattenepithelkrebs, Kehlkopfkrebs, Netzhautkrebs, Prostatakrebs, Gebärmutterhalskrebs, Gebärmutterkrebs, Hodenkrebs, Knochenkrebs, Lymphom und Leukämie ausgewählt,
2. (ii) ist die Autoimmunkrankheit aus der Gruppe bestehend aus Rheuma/rheumatischer Erkrankung, z.B. rheumatoider Arthritis (RA), Multiple Sklerose (MS), systemischer Lupus erythematodes (Lupus), Morbus Basedow, Sjögren-Syndrom, Hashimoto-Thyreoiditis, Myasthenia gravis, Vaskulitis, perniziöse Anämie und Zöliakie ausgewählt,
3. (iii) ist die Infektionskrankheit aus der Gruppe bestehend aus viraler Infektion, vorzugsweise chronischer oder persistierender viraler Infektion, bakterieller Infektion, parasitärer Infektion ausgewählt, oder
4. (iv) ist die entzündliche Erkrankung aus der Gruppe bestehend aus Atherosklerose, einer Autoimmunerkrankung, Allergie, Asthma, Zöliakie, Glomerulonephritis, Hepatitis und einer entzündlichen Darmerkrankung ausgewählt.

Preferably,

1. (i) the cancer is selected from the group consisting of skin cancer, nasopharyngeal cancer, neuroendrocal cancer, lung cancer, colon cancer, urothelial cancer, bladder cancer, liver cancer, ovarian cancer, stomach cancer, esophageal cancer, pancreatic cancer, kidney cancer, stomach cancer, esophageal cancer Head and neck cancer, brain cancer, lymph gland cancer, blood cancer, squamous cell cancer, larynx cancer, retinal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bone cancer, lymphoma and leukemia selected,
2. (ii) the autoimmune disease from the group consisting of rheumatism / rheumatic disease, e.g. rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (lupus), Graves' disease, Sjogren's syndrome, Hashimoto's thyroiditis, myasthenia gravis, Vasculitis, pernicious anemia and celiac disease selected,
3. (iii) the infectious disease is selected from the group consisting of viral infection, preferably chronic or persistent viral infection, bacterial infection, parasitic infection, or
4. (iv) the inflammatory disease is selected from the group consisting of atherosclerosis, an autoimmune disease, allergy, asthma, celiac disease, glomerulonephritis, hepatitis, and an inflammatory bowel disease.

1. (i) ist die Virusinfektion aus der Gruppe bestehend aus der Infektion mit dem humanen Immunschwächevirus (HIV), dem Hepatitis-B-Virus (HBV), dem Hepatitis-C-Virus (HCV), dem Rhinovirus (Schnupfen), dem Herpes-Simplex-Virus (HSV) und dem Respiratory-Syncytial-Virus (RSV) ausgewählt,
2. (ii) ist die bakterielle Infektion aus der Gruppe bestehend aus einer Infektion mit Borrelia burgdorferi (Borreliose), Helicobacter pylori, Mycobacterium tuberculosis, Mycobacterium leprae und Chlamydia trachomatis ausgewählt, oder
3. (iii) ist die parasitäre Infektion aus der Gruppe bestehend aus einer Infektion mit Schistosoma mansoni, Taenia crassiceps oder Leishmania mexicana ausgewählt.

Preferred,

1. (i) the virus infection from the group consisting of infection with the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV), the rhinovirus (runny nose), the herpes Simplex virus (HSV) and respiratory syncytial virus (RSV) selected,
2. (ii) the bacterial infection is selected from the group consisting of an infection with Borrelia burgdorferi (borreliosis), Helicobacter pylori, Mycobacterium tuberculosis, Mycobacterium leprae and Chlamydia trachomatis, or
3. (iii) the parasitic infection is selected from the group consisting of an infection with Schistosoma mansoni, Taenia crassiceps or Leishmania mexicana.

Preferred,
rheumatism / rheumatic disease caused by autoimmunity is selected from the group consisting of ankylosing spondylitis, recurrent polychondritis, lupus erythematosus, rheumatoid arthritis (RA), gout, inflammatory arthritis, pseudogout, juvenile arthritis, Sjogren's syndrome, scleroderma, Polymyositis, dermatomyositis, Behcet's disease, and psoriatic arthritis.

The above-mentioned procedure can be combined with chemotherapy, radiation therapy and cancer surgery. Blood warming therapy can complement chemotherapy, radiation therapy, and / or cancer surgery.

In a preferred embodiment, the patient from whom extracorporeal blood is taken at normal body temperature and to which extracorporeal blood is returned above normal body temperature has already received an operation on the cancer and / or an operation on the cancer metastases. This therapy was carried out before the heat treatment.

It is particularly preferred that in the method according to the fourth to seventh aspect a system ( 10 ) is used according to the first aspect.

It is also particularly preferred that the method according to the fourth to seventh aspect is a method that supplements chemotherapy, radiation therapy and / or cancer surgery. In other words, it is a combination therapy in which the effect of chemotherapy, radiation therapy and / or cancer surgery can be further improved.

With regard to the advantages of the various method steps, reference is made to the first aspect of the present invention.

Preferred embodiments of the invention

The making and using of the presently preferred embodiments are discussed in detail below. It should be appreciated, however, that the present disclosure provides many applicable concepts that can be encompassed by a variety of specific contexts. The The specific embodiments discussed are only intended to illustrate specific ways to make and use the concepts disclosed and do not limit the scope of the claims.

In addition, the same reference signs refer to the same technical features, unless otherwise stated. As far as the word “can” is used in this application, it means both the possibility of doing this and the actual technical implementation. The present concepts of the present disclosure are described below with respect to preferred embodiments in a more specific context, namely a system for treating cancer. However, the concepts disclosed can also be applied to other situations and / or regulations.

The foregoing has outlined rather broadly the features and technical advantages of the embodiments of the present disclosure. Additional features and advantages of embodiments of the present disclosure are described below, e.g. for the subject matter of the dependent claims. It should be understood by those skilled in the art that the concept and specific embodiments disclosed can be readily used as a basis for changing or designing other structures or methods of implementing concepts having the same or a similar purpose as those specifically discussed herein Pursue concepts. It should also be recognized by those skilled in the art that equivalent constructions do not depart from the spirit and scope of the disclosure as defined in the appended claims.

The proposed method and its embodiments must not be used for surgical or therapeutic treatment of the human or animal body and it must not be a diagnostic method practiced on the human or animal body. Alternatively, the proposed method and its embodiments may be used for the surgical or therapeutic treatment of the human or animal body and it may be a diagnostic method used on the human or animal body.

• 1 ein System zum Erwärmen oder Erhitzen von Blut,
• 2 das System zum Erwärmen von Blut im Detail,
• 3 eine erste Alternative des Systems, und
• 4 eine zweite Alternative des Systems.

For a fuller understanding of the presently disclosed concepts and their advantages, reference is now made to the following description in conjunction with the accompanying drawings. The drawings are not drawn to scale. In the drawings the following is shown:

• 1 a system for warming or heating blood,
• 2 the system for heating blood in detail,
• 3 a first alternative of the system, and
• 4th a second alternative of the system.

1 shows a system 10 to warm up blood. system 10 can according to a first alternative 10a , in the 3 is shown, or according to a second alternative 10b , in the 4th can be configured. Of course, other configurations are also possible.

• - einen Einlassschlauch 12,
• - einen Einlass I am Einlassschlauch 12,
• - einen Auslassschlauch 14, und
• - ein Auslass O am Auslassschlauch 14.

The system 10 may include:

• - an inlet hose 12 ,
• - an inlet I. on the inlet hose 12 ,
• - an outlet hose 14th , and
• - an outlet O on the outlet hose 14th .

All hoses in the system 10 can be flexible hoses made of plastic, preferably also the inlet hose 12 and the outlet hose 14th .

inlet I. and outlet O are with a person / subject 20th associated, for example, with a patient suffering from cancer. The person 20th can on a pad 22nd lying, e.g. on the surface 20th a bed, a patient bench / couch or a patient table. The surface 20th may be inclined, for example at an angle of 5 to 20 degrees with respect to a horizontal surface. The surface 20th however, it can also have a horizontal surface 20th his. It is also possible that the person 20th while performing the procedure, the system 10 used, sits.

It is possible that person 20th and the system 10 using a femoral position 24 for admission I. and for the outlet O connect to. Alternatively, take a jungular position 26th be used. Combinations of Femoral Position 24 and jungular position 26th are also possible. It is also possible to go to other locations of the person's blood vessels 20th for placing inlet I. and outlet O to use. In addition, it is possible to have more than one inlet I. and / or more than one outlet O to use.

1 also represents the heart 28 of the person 20th schematically. The body temperature Temp1 of the person 20th can be measured while performing the procedure described in this application. It is possible the body temperature Temp1 to be determined with a first temperature sensor, for example on the hand of the person 20th or at a location near the inlet I. in the system 10 is attached. Alternatively, body temperature Temp1 on the arm, in the armpit, or anywhere else on the person 20th be measured. In addition, the person's blood pressure can also 20th can be determined with a suitable sensor. EKG or EKG (electrocardiogram) sensors or electrodes can also be used on the person 20th used but are in 1 not shown.

• - ein Schlauchsystem 200, das auch Einlassschlauch 12 und Auslassschlauch 14 sowie weitere Schläuche umfasst, die in 2 nicht im Detail dargestellt sind, weil es mehrere Möglichkeiten für die Verbindung der Teile von System 10 geben kann,
• - eine Pumpe P, die an das Schlauchsystem 200 angeschlossen ist, z. B. eine Peristaltikpumpe oder eine Membranpumpe oder eine andere Art von Pumpe, z. B. eine Kreiselpumpe,
• - eine Wärmeübertragungsvorrichtung 202, die an das Schlauchsystem 200 angeschlossen ist, z.B. ein Wärmetauscher oder eine elektrische Heizung. Die Wärmeübertragungsvorrichtung 202 kann durch einen Oxygenator ersetzt werden, der auch zur Wärmeübertragung von Wärme von einer Wärmequelle auf Blut verwendet werden kann. Dies wird weiter unten ausführlicher beschrieben.
• - eine optionale Zusatzflüssigkeit 204, z.B. Wasser, das an die Wärmeübertragungsvorrichtung 202 angeschlossen werden kann, wenn z.B. ein Wärmetauscher verwendet wird, und
• - eine optionale Steuereinheit 206, alternativ ist es möglich, eine manuelle Steuerung zu verwenden.

2 illustrates parts of the system 10 to warm blood in more detail, but still on a more abstract level. Detailed relationships are in 2 not shown, but are in view of the following 3 and 4th explained. The system 10 may also include:

• - a hose system 200 that is also inlet hose 12 and outlet hose 14th as well as other hoses included in 2 not shown in detail because there are several ways of connecting the parts of the system 10 can give,
• - a pump P connected to the hose system 200 is connected, e.g. B. a peristaltic pump or a diaphragm pump or other type of pump, e.g. B. a centrifugal pump,
• - a heat transfer device 202 attached to the hose system 200 is connected, for example a heat exchanger or an electric heater. The heat transfer device 202 can be replaced by an oxygenator, which can also be used to transfer heat from a heat source to blood. This is described in more detail below.
• - an optional additional liquid 204 , e.g. water that is sent to the heat transfer device 202 can be connected if, for example, a heat exchanger is used, and
• - an optional control unit 206 Alternatively it is possible to use manual control.

Another temperature sensor can be used to determine or measure the blood temperature Temp2 of the warmed blood. It is possible, for example, to place the further temperature sensor inside the heat transfer device 202 to place.

The control unit 206 can consist of a microprocessor, a microcontroller or other device that enables the execution of commands or instructions of a software program that is stored in a digital memory, e.g. in a RAM (Random Access Memory) or in a ROM (Read Only Memory) is. Alternatively it is possible to use a control unit 206 which does not contain a processor executing a software program stored in digital memory but contains electronic circuitry without a processor. It is possible to build a digital state machine with or without a processor. States of the state machine can be changed depending on special inputs, time conditions, etc. Depending on the states, it is possible to generate appropriate output signals. The state machine can be implemented with an ASIC (Application Specific Integrated Circuit) or an FPGA (Field Programmable Gate Array), which can contain programmable connections of circuit parts.

• - Körpertemperatur Temp1 der Person 20,
• - Blutdruck der Person 20,
• - Bluttemperatur Temp2 von erhitztem Blut,
• - Zieltemperatur TT1 der Körpertemperatur Temp1,
• - Zieltemperatur TT2 von erhitztem Blut,
• - Zielwert der Flussrate TFR von Blut, z.B. durch Einlass I, durch Auslass O usw.,
• - Zielwert der Behandlungszeit Tt1, z.B. vier Stunden.

The control unit 206 can have one, a combination, or all of the following inputs / inputs:

• - body temperature Temp1 the person 20th ,
• - the person's blood pressure 20th ,
• - blood temperature Temp2 of heated blood,
• - target temperature TT1 the body temperature Temp1 ,
• - Target temperature TT2 of heated blood,
• - Target value of the flow rate TFR of blood, e.g. through inlet I. , through outlet O etc.,
• - Target value of the treatment time Tt1 , e.g. four hours.

The control unit 206 can have an automatic controller for regulating body temperature Temp1 and / or blood temperature Temp2 realize. An open loop or a more complex closed loop can be used.

It is possible with the control unit 206 to regulate further parameters automatically, e.g. the flow rate FR based on the target flow rate TFR . A cardiac technician can operate the control unit 206 while performing the procedure associated with the system 10 is carried out, supervise.

Alternatively, however, manual control, for example by a cardiac technician, can also take place. The control unit 206 may not be required in this case.

• - ein optionales Oxygenatorgerät OXY, das an das Schlauchsystem 200 angeschlossen wird,
• - ein, zwei oder mehr Reservoirs R1, R2. Das Reservoir R1 kann mit Natriumchlorid, Ringerlactat oder anderen geeigneten Lösungen gefüllt werden. Darüber hinaus kann im Reservoir R1 eine Substanz hinzugefügt werden, die die ACT (aktivierte Gerinnungszeit) verlängert. Das Reservoir R2 kann zunächst leer sein und kann dann mit Flüssigkeit gefüllt werden, die aus dem Reservoir R1 kommt, z.B. Heparin®. Dies wird im Folgenden näher erläutert. Beide Reservoirs R1 und R2 können miteinander verbunden werden.
• - eine oder mehrere Adsorber-Einheiten A1, A2 können jeweils einen Adsorber enthalten, z.B. einen Adsorber, der je nach den Bedürfnissen der Person 20 individuell vorbereitet wird.

The system 10 may also include:

• - an optional oxygenator device OXY that is attached to the hose system 200 is connected,
• - one, two or more reservoirs R1 , R2 . The reservoir R1 can be filled with sodium chloride, lactated Ringer's or other suitable solutions. It can also be in the reservoir R1 a substance can be added that increases the ACT (activated clotting time). The reservoir R2 can be empty at first and can then be filled with liquid coming from the reservoir R1 comes, e.g. Heparin®. This is explained in more detail below. Both reservoirs R1 and R2 can be connected to each other.
• - one or more adsorber units A1 , A2 can each contain an adsorber, for example an adsorber that depends on the needs of the person 20th is prepared individually.

• - einen Ausgang, der die Umdrehungen der Pumpe P steuert,
• - einen Ausgang, der die Wärmeproduktion der Wärmeübertragungsvorrichtung 202 steuert, und/oder
• - einen Ausgang, der die Sauerstoffproduktion des Oxygenatorgeräts OXY beeinflusst.

The control unit 206 can have the following outputs:

• - an output that controls the revolutions of pump P,
• - an output that controls the heat production of the heat transfer device 202 controls, and / or
• - an output that controls the oxygen production of the oxygenator device OXY influenced.

3 illustrates a first alternative 10a of system 10 . The first alternative 10a can be an oxygenator device OXY and an optional first adsorber unit A1 include. The connections shown are exemplary. Other connections are also possible.

The oxygenator device OXY can be made from a flange 300 consist. A two-chamber container can be attached to the flange 300 connected. Alternatively, a single chamber reservoir can be attached to the flange 300 connected. Adsorber unit A1 can consist of an adsorber for person 20th is individualized.

• - einen Schlauch T3 vom Oxygenatorgerät OXY zu einem Reservoir für eine Zusatzflüssigkeit, z.B. Wasser,
• - einen Schlauch T4 vom Vorratsbehälter der Zusatzflüssigkeit zum Oxygenatorgerät OXY,
• - einen Schlauch T5 an mindestens einem Anschluss des Oxygenatorgeräts OXY. Dieser Schlauch T5 kann ein Auslass für Kohlendioxid sein und/oder für verbrauchten Sauerstoff. Der Schlauch T5 kann mit dem Reservoir R1a verbunden werden, um den Sauerstoff aufzufangen, der im Moment nicht verwendbar ist.
• - einen Schlauch T6 von einer Sauerstoffquelle (O2) zum Oxygenator OXY. Der Schlauch T6 kann transparent und mit einer grünen Längslinie markiert sein.
• - einen Schlauch T8 von einer Pumpe P1 zu einem Einlass des Oxygenatorgeräts OXY. Pumpe P1 ist vorzugsweise eine Kreiselpumpe. Alternativ können für Pumpe P1 auch andere Arten von Pumpen verwendet werden.
• - ein Schlauch T10 zwischen dem Oxygenatorgerät OXY und dem Ausgang O. Der Schlauch T10 kann mit roten Bandringen markiert sein,
• - einen Schlauch T12 zwischen dem Einlass I und der Pumpe P1. Der Schlauch 14 kann mit blauen Bandringen markiert sein, und/oder
• - einen optionales Schlauch T11, der zwischen Schlauch T10 und Schlauch T12 liegt. Der Schlauch T11 kann als Brückenschlauch bezeichnet werden, siehe auch 4, Schlauch T34. Der Schlauch T11 kann meist durch eine Klemmvorrichtung geschlossen gehalten werden.

The following connections of the hose system can be used 200 within the alternative 10a give:

• - a hose T3 from the oxygenator device OXY to a reservoir for an additional liquid, e.g. water,
• - a hose T4 from the reservoir of the additional liquid to the oxygenator device OXY ,
• - a hose T5 to at least one connection of the oxygenator device OXY . This hose T5 can be an outlet for carbon dioxide and / or for used oxygen. The hose T5 can with the reservoir R1a connected to catch the oxygen that is currently unusable.
• - a hose T6 from an oxygen source ( O2 ) to the oxygenator OXY . The hose T6 can be transparent and marked with a green vertical line.
• - a hose T8 from a pump P1 to an inlet of the oxygenator device OXY . pump P1 is preferably a centrifugal pump. Alternatively you can use for pump P1 other types of pumps can also be used.
• - a hose T10 between the oxygenator device OXY and the exit O . The hose T10 can be marked with red ribbon rings,
• - a hose T12 between the inlet I. and the pump P1 . The hose 14th can be marked with blue ribbon rings, and / or
• - an optional hose T11 that is between hose T10 and hose T12 lies. The hose T11 can be called a bridge hose, see also 4th , Tube T34 . The hose T11 can usually be kept closed by a clamping device.

The oxygenator device OXY can use a temperature sensor to measure the temperature Temp2 of warmed blood. The hoses T3 and T4 can be connected to another pump for pumping the additional liquid, for example a water pump. In addition, a heated reservoir can be used for the additional liquid, for example water.

A first hose system junction N2 can be used to hose the T12 with an outlet of a reservoir R1a connect to. Another hose system junction N3 can be used to hose the T12 with an outlet of another reservoir R1b connect to. A hose system junction N4 can be used to make a connection between a hose T16 and a hose T12 to manufacture. The hose T16 is with the outlet of the adsorber unit A1 connected. An adsorber within the adsorber unit A1 can be for the patient or the subject 20th be individualized.

Another hose system junction N5 can be used to hose the T8 via a branch with the inlet side of the adsorber unit A1 connect to. The inlet side of the adsorber unit A1 can be marked with a red end cap. The outlet side of the adsorber unit A1 can be marked with a blue end cap.

1. A) Eingang I und Ausgang O sind direkt, d.h. ohne Anschluss an die Person 20 angeschlossen. Dies bedeutet, dass Eingang I und Ausgang O direkt verbunden sind, bevor System 10/Alternative 10a von System 10 an die Person 20 angeschlossen wird. In diesem Zustand befindet sich hauptsächlich Luft in den Schläuchen des Schlauchsystems 200.
2. B) Eine Klemmvorrichtung wird an der Klemmposition K1 des Schlauchs T12, d.h. zwischen den Schlauchsystemknotenpunkten N2 und N3, geklemmt.
3. C) Das Reservoir R1a enthält oder ist gefüllt mit z.B. Ringerlactat und vorzugsweise auch mit einer Substanz, die die ACT-Zeit verlängert, z.B. Heparin®.
4. D) Pumpe P1 wird eingeschaltet und erzeugt einen Sog, der Flüssigkeit vom Reservoir R1a durch das Reservoir R2a, den rechten Teil des Schlauches T12, dann durch den Einlass I, den Auslass O, durch den Schlauch T10, durch das Oxygenatorgerät OXY, durch die Pumpe P1, am Schlauchsystemknotenpunkt N2 zurück zum Reservoir R2a transportiert. Beide Reservoirs R1a und R2a können durch einen Verbindungsschlauch T19 verbunden werden. Die beiden Reservoirs R1a und R2a und ihr Verbindungsschlauch T19 können ein Füllsystem bilden. Der Luft- und Ringerlaktatfluss kann entgegengesetzt zu den Pfeilen sein, die in 3 dargestellt sind und die für den Blutfluss gelten, der später wie unten beschrieben eingeleitet wird.

How the system works 10 , especially the alternative 10a , but also the alternative 10b , can look like this:

1. A) Entrance I. and exit O are direct, ie without connection to the person 20th connected. This means input I. and exit O connected directly before system 10 / Alternative 10a from System 10 to the person 20th is connected. In this state there is mainly air in the hoses of the hose system 200 .
2. B) A clamping device is attached to the clamping position K1 of the hose T12 , ie between the hose system nodes N2 and N3 , clamped.
3. C) The reservoir R1a contains or is filled with, for example, Ringer's lactate and preferably also with a substance that extends the ACT time, such as Heparin®.
4. D) pump P1 is switched on and creates a suction, the liquid from the reservoir R1a through the reservoir R2a , the right part of the hose T12 , then through the inlet I. , the outlet O , through the hose T10 , through the oxygenator device OXY , through the pump P1 , at the hose system junction N2 back to the reservoir R2a transported. Both reservoirs R1a and R2a can through a connecting hose T19 get connected. The two reservoirs R1a and R2a and its connecting hose T19 can form a filling system. The air and lactated Ringer's flow may be opposite to the arrows shown in 3 and which apply to the flow of blood that is initiated later as described below.

• E) Die Pumpe P1 kann angehalten oder abgeschaltet werden, wenn dem Schlauchsystem 200, d.h. den Schläuchen T8 bis T18, die gesamte Luft entzogen wird. Danach können gleichzeitig oder vorher zwei Klemmvorrichtungen, z.B. medizinische Zangen, verwendet werden, um den Schlauch T10 am Ausgang O und den Schlauch T12 am Eingang I zu verschließen.
• F) ACT wird gemessen. Es wird darauf geachtet, dass die ACT z.B. über 300 Sekunden beträgt. Dies kann durch Injektion von Heparin® erreicht werden, z.B. durch einen der Katheter bei Person 20.
• G) Dann werden Einlass I und Auslass O voneinander getrennt.
• H) Einlass I wird an ein Kathetergerät angeschlossen. Der Auslass O wird mit dem anderen Kathetergerät verbunden.
• I) Die Pumpe P1 kann wieder eingeschaltet werden und die Klemmvorrichtungen an den Schläuchen T10 und T12 können entfernt oder geöffnet werden. Die Pumpe P1 kann im Vergleich zum oben erwähnten Schritt D in die andere Richtung pumpen. Die Pfeile an den Schläuchen T12, T14 zeigen die Richtung des Bluttransports an.
• J) Die Reservoirs R1a und R1b können vom Schlauchsystem 200 getrennt werden. Wenn jedoch z.B. die Herzfrequenz der Person 20 die Ringer-Laktat-Frequenz erhöht, kann dem Blut unter erneuter Verwendung der Reservoirs R1a und R2a eine andere geeignete Lösung hinzugefügt werden.
• K) Das Blut der Person 20 wird unter Verwendung des Wassers in den Röhrchen T3 und T4 erwärmt. Darüber hinaus wird das Blut der Person 20 vorzugsweise ebenfalls mit dem Oxygenatorgerät OXY oxygeniert.
• L) Am Ende der Behandlungszeit, die z.B. zwischen 2 und 6 Stunden liegt, wird das Verfahren abgebrochen.
• M) Das Verfahren kann bei der gleichen Person mehrmals wiederholt werden, z.B. mehrere Male innerhalb einer Woche.

Fluid also gets through the hose T18 , the adsorber unit A1 and the hose T16 back to the hose T12 pumped in the direction indicated by the in 3 on the hoses T16 and T18 shown arrows is displayed because the adsorber unit A1 may have some kind of one-way valve inside.

• E) The pump P1 can be stopped or switched off when the hose system 200 , ie the hoses T8 to T18 , all air is extracted. Thereafter, two clamping devices, for example medical forceps, can be used simultaneously or beforehand to clamp the tube T10 at the exit O and the hose T12 at the entrance I. to close.
• F) ACT is measured. Care is taken to ensure that the ACT is over 300 seconds, for example. This can be achieved by injecting Heparin®, for example through one of the catheters in a person 20th .
• G) Then be inlet I. and outlet O separated from each other.
• H) inlet I. is connected to a catheter device. The outlet O is connected to the other catheter device.
• I) The pump P1 can be switched on again and the clamping devices on the hoses T10 and T12 can be removed or opened. The pump P1 can pump in the other direction compared to step D mentioned above. The arrows on the hoses T12 , T14 indicate the direction of blood transport.
• J) The reservoirs R1a and R1b can from the hose system 200 be separated. However, if for example the heart rate of the person 20th If the lactate Ringer's frequency increases, the blood can be reused by reusing the reservoirs R1a and R2a another suitable solution can be added.
• K) The person's blood 20th is made using the water in the tube T3 and T4 warmed up. It also gets the person's blood 20th preferably also with the oxygenator device OXY oxygenated.
• L) At the end of the treatment time, which is between 2 and 6 hours, for example, the process is terminated.
• M) The procedure can be repeated several times for the same person, e.g. several times within a week.

Other methods of removing air from the system can also be used. Other operating methods are also possible. The filling system can also be modified if necessary.

A chemotherapy drug can be used while warming the person's blood 20th in the system 10 , 10a , 10b be admitted.

A centrifugal pump can be beneficial when using an oxygenator device OXY is used because higher pressures may be required compared to the alternative 10b that have a heat transfer device without using an oxygenator device OXY used. It is possible to have more than one blood pump within the system 10 , 10a or 10b to use. It is also possible to have more than one adsorber unit A1 , A2 within a single system 10 , 10a or 10b to use.

4th illustrates a second alternative 10b of the system 10 . The second alternative 10b can the heat transfer device 202 include, ie in the example shown a heat exchanger. In addition, the second part can 10b a filter A2 include that for the person 20th is individualized.

• - einen Einlass 400 für eine Zusatzflüssigkeit, zum Beispiel Wasser. Eine entsprechende Pumpe und eine entsprechende Heizvorrichtung für die Zusatzflüssigkeit werden verwendet, sind aber in 4 nicht dargestellt.
• - einen Auslass 402 für die Zusatzflüssigkeit, z.B. Wasser,
• - Sensorleitungen 404, die von einem Temperaturfühler innerhalb der Wärmeübertragungsvorrichtung 202 kommen und die elektrisch leitend mit der Steuereinheit 206 oder mit einer anderen geeigneten Einheit verbunden sind. Der Temperaturfühler in der Wärmeübertragungsvorrichtung 202 kann die Bluttemperatur Temp2 messen.
• - eine Schaltkurbel 406, die das Umschalten zwischen einem Spülmodus und einem Perfusionsmodus ermöglicht,
• - einen Spülanschluss PURGE, der auch zur Entlüftung verwendet werden kann,
• - einen Einlassanschluss IN, und
• - einen Perfusionsanschluss PERFUSION.

The heat transfer device 202 , ie the heat exchanger in the example shown, can consist of a filter A2 consist:

• - an inlet 400 for an additional liquid, for example water. A corresponding pump and a corresponding heating device for the additional liquid are used, but are in 4th not shown.
• - an outlet 402 for the additional liquid, e.g. water,
• - sensor cables 404 by a temperature sensor within the heat transfer device 202 come and the electrically conductive with the control unit 206 or connected to another suitable entity. The temperature sensor in the heat transfer device 202 can blood temperature Temp2 measure up.
• - a crank handle 406 which allows switching between a rinsing mode and a perfusion mode,
• - a purge connection PURGE, which can also be used for ventilation,
• - an inlet port IN , and
• - a perfusion connection PERFUSION.

There may be a fluid communication link between the inlet port IN the heat transfer device 202 and the purge connection PURGE exist, when the shift crank 406 is in rinsing mode. Alternatively, there may be a fluid communication link between the inlet port IN the heat transfer device 202 and the perfusion connection PERFUSION exist when the switching crank 406 is in perfusion mode. The heat transfer between the additional fluid and the blood in the tube system 200 can be activated in perfusion mode.

• - ein Schlauch T20 kann an den Spülanschluss PURGE angeschlossen werden,
• - ein Schlauch T22 kann an den Einlassanschluss IN und an einen Schlauchsystemknotenpunkt N6 angeschlossen werden,
• - ein Schlauch T24 kann zwischen einem Auslass einer Heizvorrichtung für Zusatzflüssigkeit 204 und einem Einlass 400 angeordnet werden,
• - ein Schlauch T26 kann zwischen dem Auslass 404 und einem Einlass der Heizvorrichtung für Zusatzflüssigkeit 204 angeordnet werden,
• - ein Schlauch T30 kann zwischen dem Ausgang einer optionalen Adsorbereinheit A2 und dem Schlauchsystemknotenpunkt N6 angeordnet werden,
• - ein Schlauch T32 kann zwischen Einlass I und Schlauchsystemknotenpunkt N6 angeordnet werden,
• - ein optionaler Schlauch T34 kann zwischen einem Schlauchsystemknotenpunkt N9 und einem Schlauchsystemknotenpunkt N10 angeordnet werden. Dieser Brückenschlauch kann verwendet werden, um Luftblasen aus dem Schlauchsystem zu entfernen, ist aber normalerweise geschlossen.
• - ein Schlauch T40 kann zwischen dem Perfusionsanschluss PERFUSION der Wärmeübertragungsvorrichtung 202 und dem Schlauchsystemknotenpunkt N10 angeordnet werden und kann sich weiter bis zum Auslass O erstrecken.

There can be following connections within the second alternative 10b of system 10 give:

• - a hose T20 can be connected to the purge connection PURGE,
• - a hose T22 can be connected to the inlet port IN and to a hose system junction N6 be connected
• - a hose T24 can between an outlet of a heater for additional liquid 204 and an inlet 400 to be ordered,
• - a hose T26 can between the outlet 404 and an inlet of the heater for additional liquid 204 to be ordered,
• - a hose T30 can between the output of an optional adsorber unit A2 and the hose system junction N6 to be ordered,
• - a hose T32 can between inlet I. and hose system junction N6 to be ordered,
• - an optional hose T34 can between a hose system junction N9 and a hose system junction N10 to be ordered. This bridge tubing can be used to remove air bubbles from the tubing system, but is usually closed.
• - a hose T40 can between the perfusion port PERFUSION of the heat transfer device 202 and the hose system junction N10 and can continue to the outlet O extend.

The hose system junction N9 is a junction from hose T32 to hose T34 . Hose system junction N10 is a connection of the hoses T34 and T40 . Medical forceps or other clamping devices can be used to clear the paths from the inlet I. and the way to the outlet O open or close if necessary while performing the procedure.

A hose pump or a peristaltic pump can be used as an alternative 10b for pump P2 be used. The pumping part of the pump P2 can be on the hose T22 between hose system junction N6 and another hose system junction N12 are located. Two or more roller devices on the hose T22 can be used to transport the blood from the inlet I. to the outlet O be used. A hose T42 can with hose system junction N12 and with an inlet of the adsorber unit A2 get connected. Here too, the inlet of the adsorber unit A2 marked with a red end cap. A clamping position K1 corresponds to the clamping position K2 .

Operation of the alternative 10b of the system 10 can be the same as the operation of the alternative 10a , as described above. To avoid unnecessary repetition, reference is made to the description above.

In other words, an extracorporeal hyperthermia perfusion method (EHP) is described. The method can combine several technical components:

EXPERIMENTS

The following is a documentation of the procedural steps of the procedure used in two patients:

Date of implementation of the procedure: December 19, 2018:

• Patient I. : 55 years old, colorectal cancer, metastases in the liver and lungs. The patient is 1.72 m (meters) tall, but weighs only 45 kg (kilograms). It is extremely thin, but the abdomen is hard, swollen and big as a handball, mainly caused by metastases in the liver. Conventional methods had shown little or no results. According to her own assessment and taking into account her living conditions, her condition is good. However, she has abdominal pain.
• Patient II: 62 years old. In July 2018, ovarian cancer was found in her body. This carcinoma, the ovaries, the spleen, the bile, part of the intestine and the peritoneum were removed. Then four types of chemotherapy were given that her body could hardly tolerate. She discontinued clinical therapy. The patient is tired and weak. She feels physically appropriate but has generalized fear.

Treatment protocol:

preparation

Time 9:45 am:

Both patients are prepared, i.e. Electrocardiography (EKG or EKG) etc. Then they are brought to the treatment room lying on treatment beds. They are wearing hospital clothes. They are connected to the monitoring devices that monitor pulse, blood pressure, etc. The ACT (Activated Clotting Time) value is also measured. The ACT value is measured with a measuring device and is a coagulation or coagulation parameter for checking the intrinsic pathway of secondary hemostasis, which is measured near the patient. According to these parameters, the blood is retained in its agglutination properties synthetically, for example with Heparin®. The electrocardiography and the measurement of pulse and blood pressure take place continuously during the entire treatment with devices available on the market.

Time 10:10 am:

Both patients are covered with a sterile cloth or cloth. A local anesthetic is injected through a drape with a hole in the thighbones of both legs. Then a catheter is inserted into the femoral vein of both legs. Both catheters are for single use only and were delivered sterilized in their packaging.

Time: 11.00 a.m.

The hose with the inlet I. and the hose with the outlet O are with the catheters of the system 10 , ie, the hyperthermia hemoperfusion device. The hoses are first filled with sodium chloride solution in order to prevent a void-containing flow, ie air, oxygen, etc. The whole system 10 can be mounted on a support frame. The support frame can be equipped with wheels, for example four wheels, which enable practical handling of the system in the treatment room.
The preparation of the patients is now complete. It is of course possible to treat only one patient at the same time or to treat more than two patients. However, every patient has his own system ( 10 ).

Implementation of the procedure

The procedure is performed under the manual control of a doctor and / or a cardio technician. A more automated control is also possible in other examples of the method. The blood now flows from the vein into the inlet at a flow rate of 1.2 liters per minute I. by an adsorber unit A1 . At the adsorber unit A1 it can be a single-use device that is prepared individually for each patient. Adsorber in the adsorber unit A1 purify the blood and remove inflammatory particles or molecules such as cytokines and chemokines. Small balls made of macroporous resin can also be placed inside the adsorber of the adsorber unit A1 (and also within the adsorber of the adsorber unit A2 ) be used. These small spheres can provide effective removal of toxic elements from the patient's blood.
The purified blood is then sent to a centrifugal pump CF or some other type of pump. The centrifugal pump CF can have a speed in the range from 2000 to 5000 revolutions per minute (rpm) or in the range from 3000 to 4000 rpm, preferably about 3600 rpm or exactly 3600 rpm. The blood can be enriched with oxygen in the centrifugal pump CF. This oxygen can pass through the oxygenator device OXY or it can be supplied from another source such as an oxygen cylinder or a hospital oxygen tubing system.
Inflammatory and / or chronic diseases can always be accompanied by a lack of oxygen in the patient's blood. The oxygen content of the blood can be increased by adding oxygen to the blood Patients are increased significantly. The normal or increased oxygen content can enable the patient's organism to keep the inflammatory states low, ie the self-healing powers of the person's body 20th to strengthen.
Water or another additional liquid 204 can be heated to 45 ° C inside a heating device, e.g. while the blood is being filtered in the adsorber unit A1 . The heating device can, for example, be a device from Elmeditec, which is usually used for other oncological procedures. The heating system for the additional liquid can comprise an additional liquid in the range from 20 liters to 70 liters. The flow rate can range from 2 liters per minute to 20 liters per minute.
The heated additional liquid 204 becomes a heat transfer device 202 and the blood is in the adjacent chamber of the heat transfer device 202 continuously heated. The warmed or heated blood is released by the heat transfer device 202 via the hose system 200 to the outlet O and through the second venous canal back into the person's body / organism 20th returned.

time 11 : 15 h (hour):

Side note: The following data refer to patient only I. . The data from patient II show a similar course.
The body temperature T1 (or abbreviated BT) is 37.2 ° C before the start of the procedure.

time 11 : 28 clock:

Body temperature T1 : 38.5 ° C
The patient feels the warmth and is allowed to drink water during the entire procedure.

time 11 : 47 clock:

Body temperature T1 : 39.3 ° C
Blood flow rate: 1.101 (liter) / minute The blood flow is continuously monitored.

time 12 :12 o'clock:

Body temperature T1 : 39.6 ° C
Blood flow rate: 1.10 1 / minute

time 12 : 30 pm:

Body temperature T1 : 40.1 ° C
Blood flow rate: 1.10 1 / minute

time 13 : Midnight:

Body temperature T1 : 40.3 ° C
Blood flow rate: 1.071 / minute
Blood pressure: 198 mmHg: 124 mmHg (millimeter Hg (hydragyrum, mercury) column)

The procedure now takes about two hours. The patient has covered herself with a blanket. She drinks. Her face and neck are very red. A damp cloth cools your forehead. The procedure is exhausting, but the patient is responsive. She speaks to the staff and to the inventor of the process described here. Of course, she feels weak and drained - also as if she had a very high fever.

time 14th : 31 clock:

Progression and health are constant.
Body temperature T1 : 40.2 ° C
Blood pressure: 1.15 1 / minute

time 14th : 55 pm:

The perfusion has ended and the whole blood is gradually released into the patient's organism 20th returned. The synthetic blood thinning, eg with Protamin®, has ended. All devices in the system 10 that were used for the EHP are switched off.

time 15th : 5 am:

Body temperature T1 : 39.5 ° C
The flexible tubes are removed from the catheter. The catheters are pulled out and the wounds from the puncture sites are closed with a bandage for about 20 minutes, for example with a “gold bandage”, ie with plastic discs that are tightened.

time 15th : 30 pm:

Body temperature T1 : 37.0 ° C.
The patient is shaking and is covered again with a blanket. The condition is good and she drinks a lot. The bandage, for example the gold bandage, is removed. The blood in the bandage has clotted. Compression bandages are applied and must be worn for about 24 hours. The compression bandages can be removed by the patient at home.

Time 4 p.m .:

The patient gets up on her own, goes to the ladies' room and puts on her street clothes. After a final medical consultation, she can go home with her companion.

All of this also applies to patient II.

Addendum:

The inventor of the procedure described here spoke to both patients several times in the weeks after the procedure was carried out. Further meetings to carry out the procedure will be agreed after further diagnostics have taken place in the meantime. Both patients say the procedures described above are strenuous. However, the burden is nothing compared to the use of the classic methods in classic hospitals and their side effects and their after-effects.

Therapy success:

• Patient I. : 55 years old, colorectal cancer, metastases in the liver and lungs. The patient received cancer surgery to remove the colorectal cancer. The patient also received chemotherapy with the aim of reducing the size of the metastases in the liver and lungs and killing off any remaining tumor cells. The chemotherapy was not entirely successful, however. In particular, the chemotherapy was not well tolerated by the patient. With the therapy, which is based on heated blood, all remaining tumor cells, especially in the blood, could be removed / killed and the metastases shrunk.
• Patient II: 62 years old, ovarian cancer. The patient received cancer surgery to remove the ovarian cancer and the uterus. The patient continued to receive chemotherapy with the aim of killing any remaining cancer cells, especially in the blood. The chemotherapy was not entirely successful, however. In particular, the chemotherapy was not well tolerated by the patient. With the therapy, which is based on heated blood, all remaining tumor cells, especially in the blood, could be removed / killed.

Further documentation of the procedural steps of the procedure used with another patient follows:

Date of implementation of the procedure: December 29, 2018:

Patient III: 62 years old, metastatic ovarian cancer. The patient has never been seriously ill, but in June 2018 she suddenly felt a stomach ache, felt weak and simply “sick”. It was diagnosed with metastatic ovarian cancer and had surgery. Your ovaries, spleen, gallbladder, part of the intestine, and peritoneum were removed. Four chemotherapies followed, which caused severe side effects in the patient. She was tired, exhausted, and discouraged. She also developed massive depression and generalized anxiety disorder. She is thin, her skin is parchment-like and pale, her hair has fallen out.

At the 29 . December 2018 she received her first extracorporeal hyperthermia perfusion therapy (EHP).

Treatment protocol:

• 9.00 h: Vorbereitung der Therapie. Nach der Blutanalyse wird die Patientin an die Überwachungsgeräte (Blutdruck, Puls usw.) angeschlossen. Der ACT-Wert wird gemessen. Das Blut wird vom Nephrologen nach diesem Parameter heparinisiert.
• 10.10 h: Die Patientin wird steril abgedeckt. Nach Verabreichung einer Lokalanästhesie werden die Katheter in die Oberschenkelvenen beider Beine gelegt. Die Zu- und Ableitungsschläuche des Hämo-Perfusionsgeräts werden angeschlossen. Auf diese Weise wird eine effektive Blutreinigung von toxischen Elementen, z.B. nach einer Chemotherapie, erreicht.

Das Blut fließt mit ca. 1,2 1/min aus der Vene und wird durch den Adsorber (einmalig verwendbar und individuell aufbereitet) geleitet. Somit ist eine effektive Blutreinigung von toxischen Elementen gegeben. Das gereinigte Blut wird durch eine Zentrifuge geleitet, wo es mit Sauerstoff angereichert wird (entzündliche und chronische Erkrankungen gehen oft mit Sauerstoffmangel einher).
In einem Wärmetauscher wird das Blut erwärmt und über den zweiten Venenkatheter mit einer konstanten Temperatur in den Körper zurückgeführt.
Die Behandlung dauert in der Regel etwa vier Stunden.
Um 14.55 Uhr wird die EHP-Therapie langsam beendet und das gesamte Blut dem Organismus wieder zugeführt. Die künstliche Blutverdünnung wird mit Protamin gestoppt.
16 h: Ende der Therapie. Nach einem Abschlussgespräch geht sie mit ihrem Mann nach Hause.

• 9.00 a.m.: Preparation for therapy. After the blood analysis, the patient is connected to the monitoring devices (blood pressure, pulse, etc.). The ACT value is measured. The blood is heparinized by the nephrologist according to this parameter.
• 10.10 am: The patient is covered with sterile drapes. After local anesthesia is administered, the catheters are placed in the femoral veins of both legs. The inlet and outlet tubes of the hemo-perfusion device are connected. In this way an effective blood purification of toxic elements, for example after chemotherapy, is achieved.

The blood flows out of the vein at approx. 1.2 1 / min and is passed through the adsorber (which can be used only once and is processed individually). Effective blood purification of toxic elements is thus given. The purified blood is passed through a centrifuge, where it is enriched with oxygen (inflammatory and chronic diseases are often accompanied by a lack of oxygen).
The blood is heated in a heat exchanger and returned to the body at a constant temperature via the second venous catheter.
The treatment usually lasts about four hours.
At 2:55 p.m., the EHP therapy is slowly ended and all of the blood is returned to the organism. The artificial blood thinning is stopped with protamine.
16 h: end of therapy. After a final interview, she goes home with her husband.

Therapy success:

The next day the patient is a little exhausted, but then things go uphill steeply. In the following months, the patient receives anabolic infusions (e.g. high-dose vitamin C and artesunate). A tumor event or cancer cells in the blood etc. could no longer be detected.
Another precautionary EHP was carried out at the end of May 2019. On June 21, 2019, she is considered cured. She's still coming for a check-up. The laboratory results are inconspicuous.

The following tables 1 to 5 summarize the therapeutic success of EHP in other patients:

Table 1: Patient IV Patient IV: born in 1965, suffering from esophageal adenocarcinoma Before EHP therapy After EHP therapy Erythrocyte sedimentation rate (ESR): 140 / not readable BSG: 16/30 C-reactive protein (CRP): 317.46 mg / l CRP: 170.58 mg / l Result: inflammation significantly reduced
CRP standard value: <5 mg / l Table 2: Patient V Patient V: born in 1953, suffering from breast cancer Before EHP therapy After EHP therapy Cholesterol (CHOL): 286 mg / dl CHO: 208 mg / dl Result: lower cholesterol levels
CHOL standard value: 110 to 220 mg / dl Table 3: Patient VI Patient VI: born in 1978, suffering from pancreatic carcinoma Before EHP therapy After EHP therapy CHOL: 224 mg / dl CHOL: 164 mg / dl CRP: 12.4 mg / l CRP: 7.85 mg / l Result: Cholesterol levels lowered, inflammation reduced
CHOL standard value: 110 to 220 mg / dl
CRP standard value: <5 mg / l Table 4: Patient VII Patient VII: born in 1958, suffering from rectal cancer Before EHP therapy After EHP therapy Iron: 14 µg / dl Iron: 52 µg / dl CRP: 58.01 mg / l CRP: 3.06 mg / l BSG: 56/96 BSG: 20/58 Thymidine kinase (THYK): 19.2 U / 1 THYK: 8.0 U / 1 Result: Iron increased as a result of the infection, the inflammation decreased and cell growth decreased.
Iron standard value: 60 to 140 µg / dl
CRP standard value: <5 mg / l
Thymidine kinase (THYK) standard value: <7.0 U / 1 Table 5: Patient VIII Patient VIII: born in 1947, suffering from breast cancer Before EHP therapy After EHP therapy Lactate dehydrogenase (LDH) isoenzyme: 595 U / l LDH: 375 U / l CRP: 264 mg / l CRP: 107 mg / l M2PK:> 100.0 U / ml M2PK: 98.8 U / ml Result: inflammation reduced
LDH isoenzyme standard value: 0 to 250 U / 1
M2PK standard value: 0 to 15 U / ml
CRP standard value: <5 mg / l

Summary:

To cure or at least alleviate diseases that are resistant to known therapies such as Lyme disease. The effectiveness should be high and there should be little or no side effects. The method described above is suitable for achieving these goals, preferably against the background of resistances to therapies which are to be found more and more frequently in infectious diseases and in oncology. The EHP is also effective in the treatment of inflammatory diseases such as autoimmune diseases. With EHP it is possible for the first time to maintain a temperature of up to 42.5 ° C in the bloodstream for more than 3 hours. This makes it possible to treat the above indications - and many others - in a highly effective manner and with little stress on the patient.

Features:

• - warming or heating of the blood itself and not by generating heat outside the body, e.g. by radiation from outside.
• - The most efficient possible cleaning of the blood and supply of the organism with natural or chemical substances that are necessary for the organism is possible because within the cycle of e.g. 4 hours a flow volume of the blood of e.g. about 360 liters is reached, i.e. of 1.5 liters per minute.
• - The use of special adsorbers that are individualized for the patient is possible.
• - Blood purification, oxygenation and gentle or mild chemotherapy can be combined within one procedure.

Although the embodiments of the present disclosure and their advantages have been described in detail, it should be understood that various changes, substitutions, and modifications can be made therein without departing from the spirit and scope of the disclosure as defined in the appended claims to deviate. For example, it will be readily understood by those skilled in the art that many of the features, functions, processes, and methods described herein can be varied while remaining within the scope of the present disclosure. Furthermore, the scope of the present application is not intended to be limited to the particular embodiments of the system, process, manufacture, method, or steps described in the present disclosure. As one of ordinary skill in the art can readily recognize from the disclosure of the present disclosure, systems, processes, manufacturing methods, methods, or steps that are presently existing or to be developed later that perform substantially the same function or substantially the same may be used in accordance with the present disclosure Achieve a result as the corresponding embodiments described here are used. Accordingly, it is intended that the appended claims include such systems, processes, methods, or steps within their scope. Furthermore, it is possible to compare the embodiments mentioned in the first part of the description with examples from the second part of the description, which relates to the 1 to 4th refers to combine.

List of reference symbols

10

System for heating blood

10a

first alternative of the system

10b

second alternative of the system

12

Inlet hose

I.

inlet

14th

Outlet hose

O

Outlet

20th

Person / subject

22nd

surface

24

Femoral position

26th

Jungular position

28

heart

Temp1

Body temperature

200

Hose system

P1

Centrifugal pump

P2

Peristaltic pump

202

Heat transfer device

204

optional additional liquid

206

Control unit

Temp2

Blood temperature of the heated blood

TT1

Target body temperature

TT2

Target temperature of the heated blood

TFR

Target flow rate

Tt1

Target time of treatment

OXY

Oxygenator device

R1a, R2a

reservoir

R1b, R2b

reservoir

300

flange

A1, A2

Adsorber unit

T3 to T42

tube

N2 to N12

Hose system junction

A.

Connection port (only in the figures)

O ₂

Oxygen reservoir

400

Inlet for additional liquid (water)

402

Outlet for additional liquid (water)

404

Sensor cables

406

Shift lever / shift crank

PURGE

Flushing connection

IN

Inlet connection

PERFUSION

Perfusion connection

K1, K2

Clamping position

Claims (26)

A system (10) for heating blood comprising: a tube system (200) having at least one inlet (I) and at least one outlet (O), wherein the tube system (200) is configured such that it carries blood between the inlet (I) and the outlet (O), and at least one heat transfer device (202) in fluid communication with the hose system (200) and configured to transfer heat to blood to increase the blood temperature (T2) within the hose system (200), wherein the system (10) is configured so that it increases the body temperature of a person (20), which can be connected to the hose system (200), by taking blood from the person (20) through the at least one inlet (I) , the blood is conducted through the tube system (200) away from the at least one inlet (I) to the at least one heat transfer device (202) and the heated blood through the tube system (200) away from the at least one heat transfer device (202) to the at least an outlet (O) is passed to increase the body temperature (Temp1) by using heated blood as a heat transfer medium. System (10) Claim 1 , wherein the system (10) is configured so that it increases the body temperature (Temp1) by at least 1 ° C, by at least 2 ° C or by at least 3 ° C. System (10) Claims 1 or 2 comprising: at least one blood pump (P) connected to the hose system (200). System (10) according to one of the Claims 1 to 3 , wherein the heat transfer device (202) comprises a heat exchanger configured to use an additional liquid (204), preferably water, preferably an additional liquid (204) having a temperature in the range of 42 ° C to 47 ° C or in the range from 44 ° C to 46 ° C or with a temperature of 45 ° C, the system (10) configured so is that the flow rate of the additional liquid through the heat exchanger is greater than 2.5 liters per minute, preferably greater than 5 liters per minute. System (10) according to one of the Claims 1 to 3 wherein the heat transfer device comprises an electrical heater. System (10) according to one of the Claims 1 to 5 comprising: an oxygenator device (OXY) configured to supply additional oxygen to the blood, the oxygenator device (OXY) preferably in fluid communication with the tubing system (200). System (10) Claim 6 wherein the oxygenator device (OXY) comprises the heat transfer device (202). System (10) according to one of the Claims 1 to 7th comprising: at least one adsorber unit (A1, A2) which has an inlet which is in fluid communication with the tubing system (200) and which has an outlet which is in fluid communication with the slaughter system (200), the blood at the outlet has been filtered compared to the blood at the inlet, the adsorber unit (A1, A2) preferably comprising an adsorber, preferably for adsorbing inflammatory molecules, toxic molecules and / or other harmful molecules. System (10) according to one of the Claims 1 to 8th comprising: a control unit (206), wherein the control unit (206) is configured to control the heat generated or transferred by the heat transfer device (202) and / or wherein the control unit (206) is configured to control the To control heat that is transferred from the blood within the tube system (200) to the body person (20), preferably by adjusting the flow rate of the blood within the tube system (200). System (10) according to one of the Claims 1 to 9 , which has at least one, an arbitrary combination or all of the following features: an input functionality for setting a target temperature (TT2) of the blood within the system (10), preferably in the range of 39 ° C to 44 ° C, preferably in the range of 40 ° C to 44 ° C, more preferably in the range from 40 ° C to 42.5 ° C, an input functionality for setting a target temperature (TT1) of the body, preferably in the range from 38 ° C to 44 ° C, preferably in the range of 40 ° C to 44 ° C, more preferably in the range from 40 ° C to 42.5 ° C, an input functionality for setting a target flow rate (TFR) of the blood, preferably in the range from 1 liter per minute to 5 liters per minute, preferably in the range from 2 liters per minute to 4 liters per minute, more preferably in the range from 1.5 liters per minute to 3 liters per minute, an input functionality for setting a target time (Tt1) for the operation of the system (10), preferably within a range of 1 hour de up to 8 hours, preferably within the range from 2 hours to 6 hours, more preferably within the range from 3 hours to 5 hours. System (10) according to one of the Claims 1 to 10 , comprising a monitoring functionality that is configured to detect or measure the temperature (Temp2) of the blood within the system (10) and / or that is configured to monitor the temperature (Temp1) of the person's body (20) captures or measures. System (10) according to one of the Claims 1 to 11 , which has at least one, an arbitrary combination, or all of the following features: at least 50 percent, at least 75 percent or at least 90 percent of the length of the tubes of the tube system (200) are thermally insulated, the control device (206) is configured to control the temperature (Temp2) of the blood within the hose system (200), preferably using a closed-loop control device, preferably a closed-loop control, which allows the temperature to exceed a target temperature value (TT2) of the blood and / or a target temperature value (TT1 ) of the body of the person (20) prevents the control device (206) is configured to control the temperature (Temp1) of the body, preferably using a closed-loop control device, preferably a closed-loop control, which allows the temperature to be exceeded about a target temperature value (TT2) of the blood and / or a Target temperature value (TT1) of the body prevented. System (10) according to one of the Claims 1 to 12 comprising a connector which is configured to receive a chemical or biochemical substance that is added to the blood in the tubing system (200), preferably a substance that is used for chemotherapy. Extracorporeal blood above normal body temperature for use in the treatment of a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis. Extracorporeal blood for use according to Claim 14 wherein the blood has a temperature (Temp2) between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C, more preferably between 40 ° C and 42.5 ° C. Extracorporeal blood for use according to Claims 14 or 15th where the blood is oxygenated blood. Extracorporeal blood for use according to one of the Claims 14 to 16 where the blood is purified blood. Extracorporeal blood for use according to one of the Claims 14 to 17th with the blood free of inflammatory or other harmful molecules. Combination of extracorporeal blood above normal body temperature and a chemotherapeutic agent for use in the treatment of cancer. Combination for use after Claim 19 wherein the blood has a temperature (Temp2) between 39 ° C and 44 ° C, preferably between 40 ° C and 44 ° C, more preferably between 40 ° C and 42.5 ° C. Combination for use after Claims 19 or 20th where the blood is oxygenated blood. Combination for use according to one of the Claims 19 to 21st where the blood is purified blood. Combination for use according to one of the Claims 19 to 22nd with the blood free of inflammatory or other harmful molecules. Combination for use according to one of the Claims 19 to 23 , the chemotherapeutic agent from the group consisting of alkylating agents, anthracyclines, cytoskeletal disruptors, epothilones, histone deacetylase inhibitors, inhibitors of topoisomerase I, inhibitors of topoisomerase II, kinase inhibitors, nucleotide analogs and precursor analogs, peptide antibiotics based on platinum and retinoids. Use of extracorporeal blood above normal body temperature as a medicament for treating a disease selected from the group consisting of cancer, an autoimmune disease, an infectious disease, an inflammatory disease and sepsis. Use of a combination of extracorporeal blood above normal body temperature and a chemotherapeutic agent as a medicament for the treatment of cancer.

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