WO2022055464A1

WO2022055464A1 - Live whole blood organ bath

Info

Publication number: WO2022055464A1
Application number: PCT/TR2021/050924
Authority: WO
Inventors: Yahya YILDIZ
Original assignee: Istanbul Medipol Universitesi
Priority date: 2020-09-11
Filing date: 2021-09-11
Publication date: 2022-03-17
Also published as: TR202014402A2

Abstract

The present invention relates to blood organ bath (BOB) developed in order to ensure that the blood maintains its properties and functions in the body, and lives in an out-of-body environment and sustains its functions.

Description

LIVE WHOLE BLOOD ORGAN BATH

TECHNICAL FIELD

The present invention relates to blood organ bath (BOB), which is developed to ensure that the blood maintains its properties and functions in the body and lives in an out-of-body environment and sustains its functions.

PRIOR ART

There are 2 methods for preserving the organ to be transplanted until transplantation in the prior art. The first method is a widely used method, which is passing a cold isotonic solution through the organ, or to protect it by leaving it in ice or ice water after washing. The second method uses perfusion devices that allow the nutrition of the tissues, organs, and cells in tissue and organ transplantation. The organ planned to be transplanted with the said perfusion device should be transplanted to the patient within 4-12 hours. In such operations, generally, tissue suitability test is applied between the donor and the recipient and then the transplantation of the organ is performed in the same center or in another center. The time of giving the organ to the recipient is vital for protecting the organ quality. In the case that this time is exceeded for different reasons, the organ that needs to be transplanted loses its function and cannot be used. Some donated organs of the donor cannot be used at that moment because there are no suitable recipients, even though rarely.

This situation shows that there is a need for systems to keep tissues and organs suitable for use for transplantation alive for more than 12 hours.

PURPOSE OF THE INVENTION

The inventors aim to develop a live whole blood organ bath that will ensure that the organs planned to be transplanted will remain alive for a longer period of time without losing their function, while aiming not only to keep the organ alive, but also to nourishing it.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to a blood organ bath, which allows the blood to live in an out- of-body environment, maintaining its properties and functions within the body, and allowing tissues and organs to live for at least 12 hours, characterized in that it comprises the following components; a dialysis bag (1) for storing the dialysis fluid a dialysate pump (2) for adjusting the rate at which the dialysate fluid passes through the dialysis filter (3), a dialysis filter (3) that filters and cleans the venous blood in the blood organ bath system, air and oxygen connections (4) for the delivery of different gas mixtures to the system according to the metabolic needs of the organ to be stored, a dialysate waste bag (5) for storing the waste dialysate fluid,

- BOB circulation circuit (6) for providing an out-of-body life support circulation circuit, filter or arterial filter (7) for retaining particles or air bubbles caused by heat change or heat difference in the system,

- total parenteral nutritional fluid (8) to meet the metabolic (energy) needs of the organ or organs stored or maintained, gas exchanger filter (9) for gas exchange between the blood and fresh gas,

- Heater, cooler, or heat regulator device (10), a blood pump (11) acting as the heart, flowmeter and mixer (12) that adjusts the and oxygen percentage, or adjusting the gas mixture and amount needed for the BOB system,

- Pressure transducer (13) for measuring pressures at different parts of the system, BOB control unit (14).

The procedures performed today in relation to blood are the collection, separation, storage, and transplantation of blood. An environment related to long-term survival has not yet been created.

However, in the BOB system according to the invention, blood is kept alive. The organ that is in contact with this blood is nourished with live blood as if it were in the body and thus, it can maintain its vitality for a long time. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a representative drawing of the blood organ bath system according to the invention. The components that make up the blood organ bath system are shown in the figure with numbers. The counterparts of the numbers in the figure are listed below.

1 : Dialysis bag

2: Dialysate pump

3: Dialysis Filter

4: Blood organ bath (BOB) air and oxygen connections

5: Dialysate waste bag

6: BOB circulation circuit

7: Arterial filter

8: Total parenteral nutritional fluid (TPN)

9: Gas exchanger filter 10: Heat regulator 11 : Heart or blood pump 12: Flowmeter 13: TPN connection 14: BOB control unit 15: Tubing set

DETAILED DESCRIPTION OF THE INVENTION

Hemodiafiltration (dialysis) system has been established in order to clean the waste in the blood organ bath (BOB) according to the invention. This dialysis system essentially acts as a kidney. Also, it can optionally dispose of some of the waste (such as bilirubin), which is one of the duties of the liver. The dialysis system performs gradual dialysis and therefore consists of multiple filtration systems, whereby it provides the removal of the blood element fragmentation products that will occur in the BOB system. For dialysis, dialysate fluid is used. The content of the dialysate fluid can be any fluid known in the art according to the substances desired to be removed, or according to the need. The dialysate fluid is stored in the bag (1) seen in 1. The dialysate fluid enters from one side of the dialysis filter (3) and exits from the other side. In other words, the blood moves on one side of the filter while the dialysate moves on the other side. Dialysate and blood passage are in the opposite directions. In other words, dialysate enters from the bottom and exits from the top while the blood enters from the top and exits from the bottom.

The dialysate pump (2) located on the BOB according to the invention is used to adjust the speed of the dialysate fluid passing through the dialysis filter (3) according to the need (such as liters/hour).

Dialysis filter (3) is a filter that can be filtered and adjusted according to the desired or needed (pore) opening. The blood that is venous or needs to be cleaned enters from one side of the dialysis filter (3) while the cleaned blood comes out on the other side and is included in the BOB system. Optionally, an intelligent centrifuge system can be added to this section or optionally, only an intelligent centrifuge system can be used instead of a dialysis filter (3).

After the blood encounters with the dialysate fluid and there is a transition between them, the structure of the dialysate changes and it absorbs the waste in the blood to a certain extent or in the desired or calculated amount. The dialysate that has become waste is collected in the waste bag (1).

The organ planned to be stored in this bath may have aerobic or anaerobic metabolism since the BOB will be used for a live organ. Different gas mixtures should be sent to the system with the help of air and oxygen connections (4) depending on the metabolic need of the organ to be stored. The main gases to be delivered may be air, for example a mixture of nitrogen and oxygen, or pure oxygen. Air and pure oxygen are mixed in different proportions to obtain the required gas concentration, if necessary. From this, 2 different gases must be supplied into the BOB with air and oxygen connection (4).

The BOB circulation circuit (6) is an out-of-body life support circuit, also called ECLS (Extra Corporeal Life Support). Circuit components comprise the following parts as shown in Figure 1 : the dialysis filter (3), the arterial filter (7), the pressure transducer (13), the gas exchanger filter (9), the heat regulator (10), and the heart pump (11). Different pumps or filters can optionally be added to this circulation circuit, if necessary.

When the BOB circuit (6), which is filled with live whole blood, is rotated within itself, the metabolism of the blood within is ensured, that is, it lives. One or more organs or tissues can be connected to the BOB circuit and ensured to live.

The arterial filter (7) retains the particle or air bubble formed due to heat change or heat difference in the system, thus, embolisations that may occur due to a particle or bubble circulating in the system are prevented.

Since BOB is an environment to be used for storing live organs, the stored organ will need metabolic (energy) and total parenteral nutritional fluid (8) is added to the system in the suitable manner.

The gas exchanger filter (9) is also referred to as the oxygenator. The gas exchanger filter (9) has a filter structure with a porous opening large enough to allow gas exchange only. The gas exchanger filter (9) has a membrane structure that provides gas exchange between blood and fresh gas.

The heat regulator (10) may also be referred to as the heater-cooler. This section ensures that the heat of the BOB is regulated, heated and cooled as desired. The said heat regulator (10) may be in any structure that exists in the known state of the art and that can provide heating and cooling of the blood organ bath.

The current form of the heart pump (11) in the BOB system according to the invention may be pulsatile or non-pulsatile. Furthermore, in an embodiment of the invention, the roller may be centrifugal radial or centrifugal axial in terms of the principle of operation of the said heart pump (11).

The flowmeter (12) in the BOB system according to the invention can also be called a gas mixer or fresh gas adjustment unit. In this unit, the gas mixture and quantity needed for the BOB system can be adjusted.

The pressure transducer (13) in the BOB system according to the invention is the unit where the pressure measurement is made. The pressure in the different points of the BOB system is measured and rearranged according to the measured values, problems such as pump flow, clogs in filters etc. can be detected and corrected with the measurements to be made here. The BOB control unit (14) located on the BOB system according to the invention can also be called the administration console and shows the functions of the components of the BOB and provides the management of the system according to the data. Most of the values in the system, such as pressure values, pump functions, gas exchanger function or oxygen content of the blood, are monitored here.

An embodiment of the invention is related to the use of the BOB system according to the invention in out-of-body organ transplantation.

An embodiment of the invention is related to the use of the BOB system in the study of the metabolism of various pharmaceutical agents in in vitro organs.

An embodiment of the invention relates to the use of the BOB system in testing various instruments or materials in in vitro organs. Such instruments and materials may be various catheters, implants, etc. medical devices or artificial organs such as artificial lungs, artificial heart pumps, etc.

The advantages and superiorities of the BOB system described within the scope of the invention are listed below.

- Functions of different organs in different environments or conditions can be evaluated in the BOB system, or functions of different organs in cases of loss of function at different levels can be evaluated, or reactions or interactions with different drugs can be evaluated. Directions or adjustments can be made by evaluating the effects or metabolisms of drugs by simulating certain levels of liver failure, heart failure, or other organ failure. The organ with the desired organ or function at the desired level in the BOB system can be monitored, directed, observed, or treated.

The desired environment can be prepared for everything to be applied to humans or living beings with the BOB system, and the things mentioned here can be, for example, all kinds of drugs or tools. Thus, the in vivo environment can be simulated in a real and desired manner, and the environment can be arranged, where quick results can be obtained. An environment where heart valve, artificial lung, or heart pump studies can be performed can be created.

The desired agent can be studied with the BOB system, without the need for in vivo animal studies or human studies. Clinical or preclinical studies can be accelerated and studies can be completed faster and at a lower cost.

An environment or laboratory where all kinds of tools, drugs and the like can be tested can be made in the BOB system. The BOB system can operate as a reference laboratory that provides impartial or realistic data. All kinds of services can be produced according to the demands from within or outside the country.

The BOB system can only be described as an organism without a head or mind, and the organism is shaped by the organs that are connected to the system. Cow functions can be examined if cow organs are attached to the organism.

The conditions of adult organs connected to the BOB system can be preserved, young organs can be grown or the functions of old organs can be provided, that is, organ aging can also be performed.

It is intended that the expression "comprises" refers to the expression "includes" within the context of this description.

Embodiments of the invention may be combined, where technically appropriate.

Embodiments are disclosed herein to include certain features/elements. The description further includes other embodiments comprising or consisting essentially of the mentioned features/elements.

Technical references such as patents and applications are included in this document by reference.

The embodiments specifically and explicitly described herein may constitute a disclaimer, either alone or in conjunction with one or more other embodiments.

Claims

CLAIMS A blood organ bath that maintains the properties and functions of the blood in the body, ensures that it lives in an out-of-body environment and that the tissues and organs remain alive for at least 12 hours or days, characterized in that it comprises; a dialysis bag (1) for storing the dialysis fluid a dialysate pump (2) for adjusting the rate at which the dialysate fluid passes through the dialysis filter (3), a dialysis filter (3) that filters and cleans the venous blood in the blood organ bath system, air and oxygen connections (4) for the delivery of different gas mixtures to the system according to the metabolic needs of the organ to be stored, a dialysate waste bag (5) for storing the waste dialysate liquid,

- BOB circulation circuit (6) for providing an out-of-body life support circulation circuit, arterial filter (7) for retaining particles or air bubbles caused by heat change or heat difference in the system,

- total parenteral nutritional fluid (8) for meeting the metabolic energy needs of the organ stored, gas exchanger filter (9) for gas exchange between the blood and the fresh gas,

- Heat regulator (10),

- Heart or blood pump (11),

- Flowmeter (12) to adjust the gas mixture and amount needed for the BOB system, pressure transducer (13),

BOB control unit (14). A blood organ bath according to claim 1, characterized in that the dialysis system comprises one or more filters. A blood organ bath according to claim 1, characterized in that it comprises the smart centrifugal system in addition to the dialysis filter (3). A blood organ bath according to claims 1-3, characterized in that air or pure oxygen or a mixture thereof is sent to the system by means of air and oxygen connections (4).

8 A blood organ bath according to claims 1-4, characterized in that the BOB circulation circuit (6) comprises the dialysis filter (3), the arterial filter (7), the pressure transducer (13), the gas exchanger filter (9), the heat regulator (10), and the heart pump (11). The blood organ bath according to claims 1-5, characterized in that the gas exchanger filter (9) has a filter structure with a porous opening large enough to allow gas exchange only. Blood organ bath according to claims 1-6, characterized in that the current form of the heart pump (11) is pulsatile or non-pulsatile. Blood organ bath according to claims 1-7, characterized in that the heart pump (11) is roller, centrifugal, radial, or centrifugal axial in terms of its principle of operation. The blood organ bath according to claims 1-8, characterized in that it is used in in vitro organ survival or organ transplantation. The blood organ bath according to claims 1-8, characterized in that it is used in studying the metabolism of various pharmaceutical agents in in vitro organs. The blood organ bath according to claims 1-8, characterized in that it is used in the testing of various instruments or materials in in vitro organs.

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