DEVICE FOR IN-SITU COOLING OF BODY-INTERNAL BIOLOGICAL TISSUES

Abstract

A method is provided for in-situ cooling of biological tissue within the body, the biological tissue being selected from the group consisting of organ tissue, blood vessel tissue and combinations thereof. The method comprises establishing a heat-conducting contact between a heat absorption zone of a cooling unit of a device for in-situ cooling of biological tissue and the biological tissue within the body, transporting thermal energy from the heat absorption zone of the cooling unit via a substance for transporting thermal energy, which is arranged within a hollow tube of the device for in-situ cooling of biological tissue, to a cooling device of the device for in-situ cooling of biological tissue, and releasing the thermal energy via the cooling device. The method allows protecting biological tissue within the body in a location-selective manner from cancer-therapy-caused damage during cancer therapy in a simple, cost-effective and low-risk manner.

Claims

1-26. (canceled)

27. A method for in-situ cooling of a biological tissue within the body, comprising: (i) establishing a heat-conducting contact between a heat absorption zone of a cooling unit of a device for in-situ cooling of a biological tissue and a biological tissue within the body, wherein the biological tissue is selected from the group consisting of organ tissue, blood vessel tissue and combinations thereof; (ii) transporting thermal energy from the heat absorption zone of the cooling unit to a cooling device of the device for in-situ cooling of biological tissue, wherein the thermal energy is transported via a substance for transporting thermal energy, which substance is arranged within a hollow tube of the device for in-situ cooling of biological tissue; and (iii) releasing the thermal energy via the cooling device.

28. The method according to claim 27, wherein the biological tissue is selected from the group consisting of parenchymal organ, blood-supplying vessel thereof, and combinations thereof.

29. The method according to claim 27, wherein the biological tissue is selected from the group consisting of gonad, a blood-supplying vessel thereof, and combinations thereof.

30. The method according to claim 27, wherein the biological tissue is selected from the group consisting of ovaries, testes, a blood-supplying and blood-draining vessel thereof, and combinations thereof.

31. The method according to claim 27, wherein the biological tissue is a biological tissue within the body of a patient to whom cancer therapy is applied during the method.

32. The method according to claim 27, wherein the heat absorption zone of the cooling unit is applied to the biological tissue within the body from outside the body in order to establish a heat-conducting contact between the heat absorption zone and the biological tissue within the body.

33. The method according to claim 32, wherein testes are cooled by placing the heat absorption zone on the testes from the outside, or ovaries are cooled by placing the heat absorption zone on an inner surface of the vagina.

34. The method according to claim 27, wherein the cooling device is arranged outside the biological tissue located within the body of a patient, wherein the thermal energy is released extracorporeally.

35. The method according to claim 27, wherein the hollow tube is guided extraperitoneally out of a patient's body by the shortest route.

36. The method according to claim 27, wherein a temperature of 8° C. to 14° C. is set at the heat absorption zone of the cooling unit.

37. The method according to claim 27, wherein the method is carried out by utilizing a device for in-situ cooling of biological tissue within the body, said device comprising (i) a cooling device; (ii) an implantable and sterile cooling unit having a heat absorption zone, wherein the heat absorption zone is suitable for establishing heat-conducting contact with a tissue within the body; (iii) at least one hollow tube comprising or consisting of plastic, wherein the hollow tube connects the cooling device to the cooling unit; and (iv) a substance for transporting thermal energy, wherein the substance for transporting thermal energy is arranged within the hollow tube.

38. The method according to claim 37, wherein the device comprises at least one further hollow tube comprising a plastic, wherein the at least one further hollow tube connects the cooling device to the cooling unit and the substance for transporting thermal energy is also arranged within the further hollow tube and wherein the at least one further hollow tube is connected to a second implantable and sterile cooling unit, wherein the second cooling unit is suitable for establishing a heat-conducting contact to a tissue within the body and has a second heat absorption zone and the device is configured to transport thermal energy from the second heat absorption zone of the second cooling unit to the cooling device.

39. The method according to claim 37, wherein the device comprises a skin port, which, reversibly or irreversibly, is connected to the at least one hollow tube, the cooling device and/or the cooling unit.

40. The method according to claim 37, wherein the device comprises a microcontroller which is configured to regulate the cooling device so that a temperature in the range from 8° C. to 14° C. prevails in the heat absorption zone of the cooling unit.

41. The method according to claim 37, wherein the device comprises a microcontroller which is configured to regulate the cooling device so that the substance for transporting thermal energy to the cooling device causes a cooling rate of 0.2 to 2.0 K/min in the heat absorption zone until a target temperature is reached in the heat absorption zone.

42. The method according to claim 37, wherein the device comprises a heating device, wherein the heating device (i) has an implantable and sterile heating unit having a heat release zone suitable for establishing a heat-conducting contact with a tissue within the body; (ii) has at least one hollow tube comprising or consisting of plastic, wherein the hollow tube connects the heating device to the heating unit; and (iii) comprises a substance for transporting thermal energy from the heating device to the heat release zone of the heating unit, wherein the substance for transporting thermal energy is arranged within the hollow tube.

43. The method according to claim 37, wherein the cooling device is configured to apply, controlled by a microcontroller of the device, a cooling power to the heat absorption zone of the cooling unit, wherein the cooling power is calculated based on the formula
P [W]=3.7 [J/mL.Math.K].Math.(310−x) [K].Math.Q [mL/sec] wherein x is the temperature in Kelvin to which cooling is to take place, and Q is the volume flow in liters of blood per second in the biological tissue to be cooled.

44. The method according to claim 37, wherein the cooling device is configured, controlled by a microcontroller of the device, to (i) increase its cooling power after starting the in-situ cooling of biological tissue within the body linearly up to a desired cooling power; and/or (ii) drop its cooling power after stopping the in-situ cooling of biological tissue within the body linearly to a desired cooling power.

45. The method according to claim 37, wherein the cooling unit has a shape or consists of a shape which is selected from the group consisting of spiral, plate(s), dome, clip, clamp, half-shell, sleeve and combinations thereof.

46. The method according to claim 37, wherein the cooling unit and/or the at least one hollow tube has/have, at least in some regions, (i) an outer surface that has a surface roughness Rz according to DIN EN ISO 4287 in the range from 50 to 800 μm; and/or (ii) pores having a pore size of 50 μm to 1000 μm, measured with electron microscopy, wherein the pores comprise at least one antibiotic.

Description

EXAMPLE

Use of a Device According to the Invention

[0163] The cooling unit of the device can be attached to the lig. cusp. ovarii or lig. ovarii proprium of a patient to be treated. If the device comprises a temperature sensor, this sensor can be attached to the mesovar of a patient to be treated. The temperature sensor enables the temperature to be monitored at the desired location and thus more precise temperature control. Cooling of the blood to 8 to 10° C. caused by the device results in rheological deprivation of the ovary and vasoconstriction of the blood vessels with the advantageous effects described.

[0164] In principle, the cooling units can have the form of cuffs or insulated clamps and, as such, can be attached to blood vessels. It is possible to attach only a small part of the circumference of the cooling cuff intraperitoneally, that is, in contact with the intestine. The advantage of the smallest possible contact area with the intraperitoneum is that a dull nerve sensation on the visceral peritoneum and the risk of forming adhesions are kept as low as possible.

[0165] The pre-cooling phase without chemotherapy takes about 30 minutes. The warm-up phase after chemotherapy is another 30 minutes. In total, a therapy session can last about 4 hours, depending on the type of chemotherapy, sometimes shorter. On average, 4 to 8 therapy sessions can be carried out at 3 to 4 week intervals. The implanted cooling units can then be removed as part of an operative laparoscopy.

[0166] Most of the hollow tube or tubes of the device are preferably deployed extraperitoneally. Direct cooling of the mesovar is conceivable, as the mesovar can easily be pulled through laparoscopically into a loop. The connection to the extraperitoneal space can be made via a peritoneal incision, which can be made transversely below the ovary. In such a case, the temperature is measured on the lig. suspensorium ovarii. Analogously, the hollow tube and part of the cuff of the device can be guided extraperitoneally. Alternatively, the cooling is realized via the lig. suspensorium ovarii, ovarii proprium and tubae uterinae. A temperature measurement can be made directly on the mesovar using a temperature sensor.

[0167] In a 2-port model or 3-port model, two skin incisions are made approx. 5 mm above the christa Iliaca anterior superior. The laparoscopic 5 mm instruments for operative endoscopy are guided intraperitoneally through the same skin incisions. The cooling lines are guided extraperitoneally through the same skin incisions. A 5 mm suprasymphyseal port is used for temperature measurement. The 10 mm incision in the umbilicus is used for intra-abdominal insertion of the cooling sets and measuring wires.

[0168] Alternatively, two operative modifications are presented below.

[0169] The peritoneal incision, which was made on the latum ligament below the ovaries, can be used extraperitoneally after the hollow tube has been laid, the ovary can be rotated about an imaginary axis frontally by 180° caudally on the mesovar by retroperitoneal transposition before the peritoneum is closed. As a result, the ovary is completely extraperitoneal, where it can be cooled, detached from the visceral pain fibers, until the end of the chemotherapy. When explanting the cooling set, the peritoneum is opened at the same point and the ovary is moved intraperitoneally on the mesovar.

[0170] A further possibility is subcutaneous epifascial transposition of the ovary at lig. infundibulopelvicum sive suspensorium ovarii. First, the uterine tuba and the lig. ovarii proprium are divided close to the uterus. Then the ovary is moved cranially and laterally to the blood supply of the lig. susp. ovarii. The fascia directly below the 5 mm port is opened to the same distance after a 2 cm skin incision, the ovary is pulled through on the vascular pedicle and placed subcutaneously epifascial. The cooling cuff can be put on here. Local anesthetic perfusion is not necessary. Upon completion of chemotherapy, the ovary is moved intraperitoneally on the pedicle.

[0171] The following approach is also possible: First, the cooling set with cuff is applied intraperitoneally through the 10 mm subumbilical port. Then peritoneal slits are made below the lig. susp. ovarii, lig. ovarii proprium and mesovar. Under laparoscopic view, an eel is introduced extraperitoneally through the 5 mm port on the side. This rail, or eel, has an eyelet at the front, which enables the cooling belt system to be threaded in. This cooling and measuring control system is passed through retrograde cutaneously and the cuffs are closed around the ovary. Care is taken to ensure that the vascular structures at the anulus internus canalis inguinalis are not injured. The cuff can be closed with a so-called “gastric banding” system.

LIST OF REFERENCE SYMBOLS

[0172] A: extracorporeal part;

[0173] B: intracorporeal part;

[0174] C, C′: cooling unit in the form of a cooling cuff on the ligamentum suspensorium ovarii;

[0175] D: cooling unit in the form of a cooling cuff on the ligamentum ovarii proprium;

[0176] E, E′: ovary;

[0177] F: line(s) to the cooling device;

[0178] G, G′: cooling unit in the form of a cooling cuff on the ovary;

[0179] 1: cooling device;

[0180] 2: cooling unit;

[0181] 3: heat absorption zone of the cooling unit (or part thereof);

[0182] 4: at least one hollow tube between the cooling device and the cooling unit;

[0183] 5: at least one further hollow tube between the cooling device and the cooling unit;

[0184] 6: communication cable from temperature sensor;

[0185] 7: temperature sensor;

[0186] 8: coupling unit (for example, skin port);

[0187] 9: tissue (to be cooled, for example, blood vessel to ovary);

[0188] 10: substance for the transport of heat (for example, liquid refrigerant);

[0189] 11: insulation layer;

[0190] 12: heat release zone of a heating unit of a heating device.

[0191] 13: at least one hollow tube between the heating device and the heating unit.