Equipment and method for perfusing normothermic intraperitoneal chemotherapy

Abstract

The present invention relates to equipment (device) and a method for perfusing or infusing therapeutic agents in a closed system, recirculating the fluid used during the treatment and the drained fluids back to the original containers. The device of the present invention is arranged so as not to discard chemical and biological fluids drained from the patient into other containers or into the sewage system, using for this purpose a set of valves, clamps, forceps, a pump, tubes and catheters to recirculate therapeutic agents, such as chemotherapeutic agents, in the individual to be treated and subsequently return the drained fluids safely to the original bags, thereby providing safe management of toxic waste for the hospital environment and the environment.

Description

"EQUIPMENT AND PROCESS FOR NORMOTHERMIC INTRAPERITONEAL CHEMOTHERAPY PERFUSION" FIELD OF THE INVENTION

[0001] The present invention relates to equipment, system and process for normothermic intraperitoneal chemotherapy perfusion, comprising a set of reservoir bags that will contain the perfusate, the liquid necessary to dilute the chemotherapy drug to be applied to the abdominal (peritoneal) or thoracic (pleural) cavity of the patient, tubes (which may be made of PVC), valves, clamps, simple linear connectors and with Luer Lock, Y-connectors and catheters capable of performing the perfusion of chemical and biological fluids that will be perfused together with the chemotherapy drug into the abdominal or thoracic cavity, and which, after the end of the treatment, will return to the original reservoir bag, avoiding disposal in inappropriate locations. The fluids drained back into the reservoir bag will be disposed of together with the bag in the appropriate locations for toxic waste in hospital environments.This reduces the risk of contamination in these areas during the treatment of peritoneal neoplastic disease of gastric, ovarian, colorectal, appendiceal origin, peritoneal neoplasia, malignant ascites, and other gastrointestinal or pleural diseases. It also reduces the risk of environmental contamination.

[0002] The present invention can be applied to any type of medical or veterinary procedure that uses perfusion devices to infuse medications into patients being treated, and where there is a need for drainage and disposal of the perfused fluids (post-treatment, which will still contain part of the perfused therapeutic agent). This is provided that such fluids can fit in the same container as the inserted therapeutic agent (e.g., chemotherapy drug). This drained fluid is susceptible to contaminating the team of doctors or veterinarians and healthcare professionals (operating room technicians, perfusionists, surgical instrument technicians) involved in performing the technique and, therefore, must remain within a closed system, returning to the reservoir bag or any other original container. Since these are manufactured to receive and maintain this type of fluid, the procedure becomes safer and more environmentally friendly. FUNDAMENTALS OF THE INVENTION

[0003] Globally, in 2020, an estimated 1 million new cases of stomach cancer were expected (5.6%), making it the fifth most common type of cancer. In terms of mortality in Brazil, in 2020, there were 13,850 deaths from stomach cancer, corresponding to 6.54 deaths per 100,000 Brazilians.

[0004] Gastric cancer (GC) is classified according to its stage, that is, how advanced it is and the level of its spread in the body. Peritoneal carcinomatosis (PC) and positive cytology (C+) are classified as metastatic disease or stage IV, according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, eighth edition. These forms of metastasis are associated with a poor prognosis, with median overall survival (OS) rates of 4-8 months [Thomassen I, van Gestel YR, van Ramshorst B, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014;134(3):622-8; Tan HL, Chia CS, Tan GH, et al. Gastric peritoneal carcinomatosis a retrospective review. World J Gastrointest Oncol. 2017;9(3):121-8; Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCCcancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017; 67(2): 93-9],

[0005] Recent publications supporting this claim have shown that the peritoneum is the most common site of metastatic disease, and that more than 30% of patients who appear potentially resectable on imaging studies [Ikoma N, Chen HC, Wang X, et al. Patterns of initial recurrence in gastric adenocarcinoma in the era of preoperative therapy. Ann Surg Oncol. 2017;24(9):2679-2687; Ikoma N, Blum M, Chiang YJ, et al. Yield of staging laparoscopy and lavage cytology for radiologically occult peritoneal carcinomatosis of gastric cancer. Ann Surg Oncol. 2016;23(13):4332-7], Metastatic peritoneal disease, whether PC or C+, is one of the most important targets to be treated to prolong survival in patients with stage IV gastric cancer.

[0006] Patients with gastric cancer with CP or C+ are usually treated with systemic chemotherapy in a palliative manner, as are patients with other distant metastases. However, considering peritoneal dissemination as the sole focus of spread, it may be reasonable to address metastatic lesions and free neoplastic cells in the peritoneal cavity directly with intraperitoneal chemotherapy.

[0007] Intraperitoneal chemotherapy (IPTC) of antineoplastic drugs aims to increase the dose and duration of exposure to intra-abdominal tumor cells while minimizing systemic toxic effects. Indeed, intraperitoneal (IP) administration has been shown to result in higher drug concentrations and a longer half-life in the peritoneal cavity compared to intravenous administration, although this is affected by a variety of biophysical parameters, including molecular weight, charge, and solubility [Dedrick RL, Myers CE, Bungay PM, DeVita VT Jr. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978;62:1-11; Markman M. Intraperitoneal antineoplastic drug delivery: rationale and results. Lancet Oncol. 2003;4:277-83].

[0008] Repeated intraperitoneal (IP) infusion of antineoplastic drugs using an implantable port system (long-term catheter) has been employed for some years; however, attention is once again turning to repeated intraperitoneal chemotherapy (RIPEC) using taxanes such as paclitaxel (PTX) and docetaxel (DTX). IP taxanes have been combined with systemic chemotherapy as neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), and the results have already been summarized in the article by Kobayashi et al. [Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Gastric Cancer. 2017;20(Suppl 1):111— 21]. This approach resulted in a median survival time (MST) of 15.1–24.6 months and a 1-year survival rate of over 70%, which are considerably better than the results with systemic chemotherapy or HIPEC (hyperthermochemotherapy intraperitoneal) [Ishigami H, Kitayama J, Kaisaki S, et al.Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol. 2010;21:67-70. 19-26; Fujiwara Y, Takiguchi S, Nakajima K, etal. Intraperitoneal docetaxel combined with S-1 for advanced gastric cancer with peritoneal dissemination. J Surg Oncol. 2012;105:38-42; Fushida S, Kinoshita J, Kaji M, et al. Phase l / ll study of intraperitoneal docetaxel plus S-1 for the gastric cancerpatients with peritoneal carcinomatosis. Cancer Chemother Pharmacol. 2013;71: 1265- 72; Yamaguchi H, Kitayama J, Ishigami H, Emoto S, Yamashita H, Watanabe T. A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S-1 for treatment of gastric cancer with macro- scopic peritoneal metastasis. Cancer. 2013;119:3354-8; Ishigami H, Fujiwara Y, Fukushima R, et al. Phase III study of intraperitoneal paclitaxel plus S-1 / paclitaxel compared with S-1 / cis- platin in gastric cancer patients with peritoneal metastasis: PHOE- NIX-GC trial. J Clin Oncol. 2016;15(suppl):4014; Fujiwara Y, Ishigami H, Miwa H, et al. Phase II study of intraperitoneal paclitaxel plus S-1 / oxaliplatin for gastric cancer with peritoneal metastasis: SOX+IP PTX trial. J Clin Oncol. 2016; 15 (suppl):4040; Fukushima R, Ishigami H, Miwa H, et al. Phase II study of intraperitoneal docetaxel plus capecitabine / cisplatin for gastric cancer with peritoneal metastasis: XP+IP DOC trial. J Clin Oncol. 2017; 15 (suppl):4039; Cho H, Ryu MH, Kim KP, et al.Phase l / ll study of a combination of capecitabine, cisplatin, and intraperitoneal docetaxel (XP ID) in advanced gastric cancer patients with peritoneal metastasis. Gastric Cancer. 2017;20:970-7],.

[0009] Repeated doses of PTX IP (Intraperitoneal Paclitaxel) can eradicate deeper tumor cells, and changes in the peripheral structure of tumor nodules can reduce intratumoral pressure and increase the efficiency of delivery of systemically infused antineoplastic drugs, which may be another important mechanism to explain the remarkable antitumor effects against C+ and CP. When patients show a good response to this locoregional therapy and gastric resection is performed, the TMS reached 26.5-30.5 months.

[0010] Another important advantage of RIPEC (repeated normothermic intraperitoneal chemotherapies) is its relatively mild toxicity compared to HIPEC. According to one series, grade 3 / 4 neutropenia occurred in 21% to 50% 21-28. As this strategy can cause a notable reduction in macroscopic tumors, RIPEC can be expected to be more effective in treating patients with PC and / or C+. In fact, cytology was converted to negative in 71% to 97% of patients with PC, 19-25 which has never been achieved with other methods in previous reports. This therapy may be a promising strategy for the prevention of peritoneal recurrence in CG with serous exposure, which is a staging with a high risk of recurrence.

[0011] Controlled drug administration via infusion devices has been playing a crucial role in clinical practice, allowing for the precise delivery of therapeutic agents directly into the patient's body. This type of medical procedure, often associated with oncology, peritoneal dialysis, and other treatments, offers an effective approach to ensuring the proper concentration of medications, optimizing therapeutic outcomes.

[0012] Devices designed for perfusion vary in complexity and application, ranging from sophisticated implantable pumps to disposable kits used in daily clinical procedures. A common characteristic of these devices is the ability to administer medications directly into the bloodstream, promoting a faster and more effective therapeutic response compared to conventional methods.

[0013] Advances in this area have focused not only on the precision of drug delivery, but also on minimizing the impact on the patient, providing greater comfort and reducing the need for human intervention. This includes automated systems that dynamically monitor and adjust infusion rates, ensuring the stability of the therapeutic concentration throughout treatment.

[0014] Furthermore, the diversity of devices found in the state of the art reflects the growing understanding of specific clinical needs in different fields of medicine, which demand improvements and enhancements to this type of treatment. A wide variety of applications are found, and the versatility of these technologies stands out, ranging from systems dedicated to peritoneal dialysis, through devices for collecting blood components, to implantable pumps for chemoradiotherapy in oncology, with one or multiple bags that allow for longer treatment times.

[0015] Document CN109172937A, for example, introduces an implantable chemoradiotherapy pump, emphasizing the localized retention of treatment through an elastic storage bag, minimizing systemic effects. Document US4655742A describes a process and apparatus for processing body fluids, focusing on plasmapheresis, and even mentions a safe disposal system for the collected fluids. Document DE3249318A1 presents a device for the withdrawal and reinfusion of autologous blood, highlighting the need to minimize damage and the use of non-returnable valves. In turn, US2004147865A1 develops a blood filtration and processing system for red blood cell collection, emphasizing efficient and safe collection. BR9606629A, which addresses a peritoneal dialysis system with a variable depression device, can also be mentioned, highlighting the importance of automatic control.

[0016] Overall, in this period of medical innovation, the continuous evolution of perfusion and infusion devices not only redefines the standards of medical care but also improves the quality of life for patients. This comprehensive overview reflects the critical importance of these devices in the context of administering advanced medical treatments and signals a promising outlook for the future of drug therapy.

[0017] Among the wide range of devices for perfusion and infusion, the growing importance of systems dedicated to normothermic intraperitoneal chemotherapy perfusion stands out. This method of chemotherapy administration is of significant relevance, especially in the context of cancer treatment, offering distinct advantages compared to conventional approaches.

[0018] Normothermic intraperitoneal chemotherapy infusion involves the direct infusion of antineoplastic agents into the peritoneal cavity, where the temperature is maintained at physiological levels. This approach aims to optimize therapeutic efficacy by promoting prolonged retention of chemotherapeutic agents at the tumor site. By allowing chemotherapy to act locally, normothermic intraperitoneal infusion minimizes adverse systemic effects, providing substantial benefits in terms of treatment response.

[0019] Specialized devices for this type of perfusion are precisely designed to ensure uniform distribution of medications within the peritoneal cavity. A distinctive feature of these devices is their ability to provide controlled drug release, prolonging the chemotherapy's residence time at the tumor site and consequently improving treatment efficacy.

[0020] This normothermic approach not only maximizes therapeutic efficacy but also contributes to minimizing side effects, improving patient tolerance to treatment. Furthermore, the use of specific devices for normothermic intraperitoneal chemotherapy infusion stands out as a promising strategy for cases of abdominal cancer, where a localized response is crucial.

[0021] Despite notable advances in normothermic intraperitoneal chemotherapy infusion, a significant challenge remains in the proper management of peritoneal cavity fluids following the administration of chemotherapeutic agents. These fluids, often contaminated with drug residues and biological components, present not only hospital risks but also environmental concerns that require specific management approaches.

[0022] Traditionally, the disposal of these bodily fluids is treated with caution due to their potentially harmful nature. The presence of chemical and biological residues makes these liquids a challenge for conventional disposal processes, and they can pose risks to both healthcare professionals and the surrounding environment.

[0023] Traditional disposal methods may include the collection and treatment of these fluids before release into the hospital sewage system. For example, patent application WO8802641 A1 describes methods and systems for collecting blood components. The patent application reports methods that utilize a set of disposable and reusable structures, with an emphasis on energy autonomy.

[0024] US patent US2017136181A1 describes an assembly for a drug delivery device, comprising a dispensing container and a reservoir container, allowing the dispensing container to be refilled from the reservoir.

[0025] We can also mention document US2017186584A1, which presents packaging for storing and dispensing liquids, emphasizing the complete expulsion of contents through fluid pressure, with potential application in parenteral solutions.

[0026] However, these processes require rigorous measures to ensure the neutralization of chemical components and the effective elimination of any biological material that could compromise safety.

[0027] Furthermore, growing environmental awareness highlights the need for more sustainable strategies to deal with this waste, since the presence of chemicals in water and soil can have lasting impacts on the ecosystem.

[0028] Innovative technologies are being explored to address these concerns. Advanced filtration systems and specific treatment methods are being developed to mitigate the risks associated with the disposal of these fluids. However, a continuous effort to improve existing practices and seek more effective and sustainable alternatives is essential.

[0029] Surprisingly, the solutions described in the state of the art in the field of intraperitoneal chemotherapy perfusion and infusion have a significant gap. None of them addressed the possibility of redirecting post-treatment fluids back to the original bags that contained the chemotherapy drugs and the perfusate fluid.

[0030] State-of-the-art systems are more focused on improvements in administration, control of infusion or perfusion without return of chemotherapy drugs, and disposal of fluids. For example, EP0815882A2 details a peritoneal dialysis device, highlighting a system of joints and tubing for the disposal of drained fluid, or EP1829569A2 develops a PD-cycler and tubing assembly for the automatic transfer of remaining contents to a waste receptacle. We can also mention the international patent application WO 95 / 20985, which proposes an apparatus for peritoneal dialysis, including a heat bag and a disposal bag, with emphasis on flow monitoring. However, the reincorporation of treated waste into its original containers has not yet been addressed.

[0031] It is important to highlight that there are solutions focused on recirculation and closed systems, especially when involving methods known in other fields, such as hemodialysis, where the practice of recirculating blood after processing is common. As we can see in document BR8302567A, which describes a device for receiving and reinfusing the patient's own blood, using a rigid and flexible container, very similar to the bags used in perfusion. However, unlike hemodialysis procedures, where recirculation (with the removal, processing, and return of blood to the patient) is an established practice, in perfusion systems, the focus is on the safe disposal of fluids after treatment, without explicit consideration of reintegrating them into the treated individual.

[0032] This distinction highlights a significant opportunity for improvement in intraperitoneal chemotherapy perfusion and infusion, or even in other body cavities where post-treatment disposal is considered. By incorporating the concept of recirculation, inspired by successful practices in other medical contexts, future developments could establish a new standard of efficiency, sustainability, and responsibility in the management of these post-treatment fluids, resulting in additional benefits for clinical practice and the environment.

[0033] In this sense, it would be interesting to develop processes, systems, and devices that address this lack of consideration for a closed-loop system, where post-treatment fluids should be reintegrated into their original containers, such as the perfusate and chemotherapy drug reservoir bags themselves. This would stand out as a significant opportunity to improve this approach, offering additional benefits such as waste management, enhanced hospital safety, and reduced exposure of all medical or veterinary staff and healthcare professionals involved in treatment to hazardous waste. It would also contribute to environmental protection. BRIEF DESCRIPTION OF THE INVENTION

[0034] The present invention therefore relates to EQUIPMENT AND PROCESS FOR NORMOTHERMIC INTRAPERITONEAL CHEMOTHERAPY PERFUSION Designed for the treatment of peritoneal neoplastic disease of gastric, ovarian, colorectal origin and / or malignant ascites, comprising a set of (PVC) tubes, flow-control clamps and catheters capable of performing the perfusion of chemotherapeutic agents into the abdominal (peritoneal) and / or thoracic (pleural) cavity and subsequently returning the drained chemical and biological fluids to the original container, representing a closed-loop system. The invention is capable of achieving safer and more efficient management of intraperitoneal chemotherapeutic perfusion waste, generating advantages from the point of view of environmental and hospital responsibility, thus consolidating a comprehensive and sustainable vision in the field of contemporary medicine and veterinary medicine.

[0035] The constant evolution of these perfusion devices reflects the relentless pursuit of more effective and safer solutions, not only patient-centered but also encompassing the entire hospital environment in the field of oncology.

[0036] In this sense, the present invention relates to a device for perfusing therapeutic agents into the body cavity to be treated, such as the abdominal (peritoneal) or thoracic (pleural) cavity, preferably normothermic, and in a closed cycle. That is, returning the perfusate (after treatment) from the treated patient to the original bag(s) of therapeutic agents (represented in the example in Figure 1 by rectangles A and B).

[0037] The closed system plays a fundamental role in redefining treatment paradigms and continuously improving clinical outcomes for medical teams and cancer patients, since returning the perfusate to the reservoir bag is more suitable for storing the perfusate containing the chemical and biological substances used in treatment, avoiding disposal in other containers or even in the local sewage system, which would generate risks to the professionals conducting the medical intervention, as well as to hospital safety and the environment.

[0038] In this sense, the first embodiment of the invention refers to a perfusion device, preferably normothermic, which has a closed-loop construction. That is, it refers to any device capable of delivering medication to the patient and returning the fluids from this treatment back to the original containers. This embodiment focuses not only on the effective administration of therapeutic agents, such as chemotherapeutic agents, into the body of the individual to be treated (e.g., into the abdominal (peritoneal) or thoracic (pleural) cavity of humans or animals), but also on the efficient recirculation of the perfusate back to the original reservoir bags, ensuring the hospital and environmental safety of the procedure.

[0039] In an optional presentation, the device may be more advantageous if manufactured with transparent material, allowing visualization of the flow during the procedure by the medical team and the perfusionist. However, other existing or future flow control techniques can be implemented by a specialist in the field.

[0040] The device can be manufactured with pipes of different materials (e.g., PVC and other polymers), gauges, and have varying sizes in certain segments, provided they comply with the operational standards appropriate to this procedure. Therefore, the materials, sizes, and gauges presented here are merely illustrative examples and are subject to modifications and adjustments by a qualified technician.

[0041] In this sense, in a second embodiment of the invention we have a specific device, a bifurcated medical / veterinary unit, developed to be one of the possible embodiments of the present invention, consisting of: • one or more storage bags (rectangles A and B in figure 1) of the perfusate fluid to be infused into the patient's abdominal (peritoneal) or thoracic (pleural) cavity (21); • In the case of only two bags, two PVC tubes (5 and 6) of approximately 40 cm, have a flow-cutting clamp on each (3 and 4) and at the terminal portion have a connector with a perforator (1 and 2) with a protective cap that are connected to the bags (A and B) containing the perfusate that will be infused and perfused into the abdominal or thoracic (pleural) cavity; • In the single portion of this Y (7) of % a PVC tube of approximately 40 cm is connected, which connects to another Y connector (9) of % which in its two other parts connects to two PVC tubes (10 and 12) of approximately 40 cm in each of the parts; • A PVC tube (12) with a 1 / 4 inch gauge and 100 cm in length connected at the distal end to a 1 / 4 inch PVC linear connector which, in turn, is connected to the fenestrated tubular aspirator tube (19) of 28 French (French refers to a unit of size for tubular drains) which is located inside the patient's abdominal cavity (21); • In the proximal portion there is a flow-cutting clamp (13); • This tube is connected to a Y connector (9) of % (quarter inch gauge); • In the other portion of the Y-connector, another PVC tube (10), preferably of a more malleable consistency, measuring approximately 60 cm in length, is coupled to the roller (18) of the perfusion pump (11); • The distal portion of this tube (10) connects to a connector, preferably of the straight luer lock type (17), through which the chemotherapeutic drug is injected, which will be connected to a PVC tube measuring approximately 100 cm in length (16) and which is connected to a linear PVC connector of %, which, in turn, is connected to the fenestrated tubular infusion tube (20) of 28 F, which will remain inside the patient's abdominal or thoracic cavity (21).

[0042] Thus, the bifurcated device, described above and detailed further on, is capable of performing the perfusion process in a closed cycle, which begins with the infusion of the perfusate and the therapeutic agent (chemotherapeutic) into the peritoneal cavity through a tube connected to an infusion catheter. Simultaneously, the circulation tube (12) is connected to an aspiration catheter (19), also inserted into the peritoneal cavity. This aspiration catheter, connected to the perfusion pump, provides additional safety, minimizing the risk of frequent disconnections in improvised circuits. The drains placed in the peritoneal cavity are of the fenestrated tubular type, allowing efficient aspiration without the risk of aspiration of intestinal loops, providing greater safety to the treatment.

[0043] In this preferred device, recirculation is performed in an integrated manner, where the aspirating catheter has a Y-connection, connected to an infusion system that facilitates rapid and safe recirculation of the perfusate.

[0044] The tubing is connected to one part of the Y-shaped device, while another tube is connected to another branch of the Y-shaped device, containing a flow-control clamp in the proximal portion. From the single-piece Y-shaped device, an additional tube extends, connected to a straight luer-lock connector, allowing the perfusate to be returned to the patient.

[0045] In a third embodiment of the invention, the closed-loop perfusion process itself is included, which begins with the step of: 1) preparing the device or equipment (Figure 1); 2) Infusion or perfusion of the therapeutic agent (chemotherapeutic agent) into the peritoneal cavity through a tube connected to an infusion catheter; 3) Drainage or aspiration of fluids after waiting the appropriate treatment time for each therapy; and 4) Efficient recirculation of fluids to the original containers, in which the aspirated liquids are directed back to the original bags of medication that were used in the treatment.

[0046] The bags (represented by rectangles A and B in Figure 1), which contained the perfusate fluid associated with the chemotherapy drug used in treatment, will now contain material from the patient and will be disposed of as hospital waste, ensuring greater safety in the process.

[0047] At the end of the treatment process, the perfusate and chemotherapy drug used are drained into the same solution bags (Figure 1) used in peritoneal dialysis, minimizing the risk of leakage and environmental contamination.

[0048] Finally, this equipment and process are part of a closed system, containing tubes, connectors, catheters, valves, clamps, perforators, pumps, and bags that allow for a comprehensive and safe approach to the administration of chemotherapy or other medications into the abdominal or thoracic cavity, integrating the efficient and sustainable recirculation of the perfusate fluid. BRIEF DESCRIPTION OF THE FIGURES

[0049] The figure mentioned below represents a particular embodiment of the invention, without its mention imposing any limitation beyond those contained in the claims. Figure 1 - illustrates a simplified view of the equipment attached to the patient (21), containing two perfusate bags (rectangles A and B), which contain the perfusate fluid that will be used to dilute the medication(s) to be infused and subsequently aspirated from the patient's peritoneal or thoracic (pleural) cavity, having the following components: two perfusate bags represented by rectangles A and B, which will be attached respectively to two tubes (5 and 6), which may have a diameter of 1 / 4 inch and a length of approximately 40 cm, which have perforators (1 and 2) at their proximal ends (necessary to remove the seal from the hermetic bag) and at the distal end is attached the Y connector (7), which may be 1 / 4 inch; in the tubes (5 and 6) there are flow-control clamps (3 and 4) that block the passage of the fluid during perfusion;tube (8), which can be % inch in size and 40 cm long, which connects at its upper end to the insulated portion of the first Y connector (7), to the distal part of the tube (8) and at its lower end connects to a second Y connector (9), in one of the bifurcated portions of this second Y connector, it will be connected to the flexible soft tube measuring 60 cm (10) that passes through the roller (18) of the pump (11); the second branch of the second Y (9) is connected to a PVC tube which can be % inch with about 100 cm in length (12); a flow control clamp (13) located on the PVC tube (12), right after the second Y connector (9), and at its other end connects with a straight % connector (14); which will be connected to the 28 F flexible PVC fenestrated aspirating tube (19) which aspirates (but can also infuse, drain or even reinfuse) the perfusate into the patient’s abdominal cavity (21);In the other portion of the flexible tube (10), which is inserted into the roller (18) of the pump (11), it connects to the straight connector with luer-lock (17) which can be made of PVC tube (16) which can be 100 cm long, which connects to the straight connector with luer-lock (17); at the other end it connects to the straight connector (15) which will be connected to the fenestrated flexible PVC tube of 28 Fr, aspiration catheter (20), which drains (but can infuse or reinfuse) the perfusate into the abdominal or thoracic cavity of the patient (21). Closing the circuit with the patient (21), without being limited to an exact flow, which should follow medical practice, and allows, at the end, the return of fluids to bags A and B. DETAILED DESCRIPTION OF THE INVENTION

[0050] A description of the invention follows in order to facilitate understanding of the present invention, without such description imposing any limitation on it beyond those expressed in the appended claims. The present invention, therefore, relates to a NORMOTHERMIC INTRAPERITONEAL CHEMOTHERAPY PERFUSION EQUIPMENT AND PROCESS, specially developed to treat peritoneal diseases of gastric, ovarian, colorectal origin and malignant ascites. The system comprises a set of valves, clamps, forceps, tubes, catheters, pumps and hospital or veterinary equipment, allowing the safe perfusion of chemotherapeutic agents into the peritoneal cavity and, subsequently, the return of the drained fluids to the original bags, creating a closed cycle.

[0051] This device represents a significant evolution in the administration of therapeutic agents, providing efficient and safe management of chemotherapy infusion waste in body cavities, such as intraperitoneal administration. By adopting a closed-loop system, the present invention minimizes environmental and hospital risks, consolidating a sustainable approach in contemporary medicine and veterinary medicine.

[0052] The device is primarily intended for normothermic treatment (physiological temperature) and it is suggested that it be manufactured with transparent material, or that it incorporate techniques that allow for visual or computational (sensors) monitoring of the flow.

[0053] The preferred solution features a Y-shaped bifurcated configuration with two channels, each equipped with a piercing tip, cap, and flow-control clamp. Safe recirculation of the perfusate fluid back to the original bags is facilitated by Y-connections, tubing, rollers, and clamps, ensuring precise flow control.

[0054] To perform closed-loop perfusion, the following steps are generally followed: it begins with the infusion of the perfusate and subsequent infusion of the chemotherapeutic agent into the peritoneal or thoracic cavity, using an infusion catheter (19, or 20) connected to a tube (12). Simultaneously, a second tube (16) connected to an aspiration catheter (20, or 19), also inserted into the patient's peritoneal cavity (21), is connected to a perfusion pump (11), ensuring greater safety and reducing frequent disconnections.

[0055] The infusion and aspiration catheters (19 and 20) are equipped with a fenestrated tubular drain, allowing for efficient drainage and avoiding the risk of aspiration of intestinal loops. Recirculation is integrated, connecting the aspiration catheter to an infusion system to facilitate the rapid and safe return of the perfusate fluid.

[0056] At the end of treatment, the perfusate and chemotherapy drug are drained into the same solution bags (A and B) used in peritoneal dialysis, minimizing the risk of leakage and environmental contamination. EXAMPLES

[0057] The following examples, described with the aid of Figure 1 (attached), are given only as examples and illustrations of particular embodiments of the invention, without imposing restrictions on it beyond those contained in the appended claims. Example 1 - Closed-loop normothermic perfusion device

[0058] One of the preferred embodiments of the equipment (device) of the present invention would be its manufacture in crystal PVC, having two channels (5 and 6), each measuring 35 cm in length, also made of crystal PVC, with a diameter of 1

[0059] Each line has a piercing tip (1 or 2) to be attached to the bag (A or B) containing the perfusate fluid that will be infused into the peritoneal cavity.

[0060] The piercing tips have caps and a flow-cutting clamp on each of the channels (3 and 4). This equipment is connected to a 1 / 4” PVC Y-connector (7) which is connected to a 1 / 4” diameter clear PVC tube measuring 40 cm in length (8), which is connected to one of the branches of the double portion of the 1 / 4” PVC Y-connector (9).

[0061] On the other branch of the 1 / 4” PVC Y-connector is connected a crystal PVC tube (12) with a diameter of 1 / 4” measuring 100 cm in length, having at the proximal portion to the Y branch a flow control clamp (13).

[0062] In the single part of the Y, a flexible and soft crystal PVC tube (10) with a diameter of 1 / 4” measuring 60 cm and at the distal part of this tube is connected to an optional straight luer lock connector (17) of crystal PVC with a diameter of 1 / 4” which is connected to a crystal PVC tube with a diameter of 1 / 4” measuring 100 cm in length (16).

[0063] More specifically, the illustrative example of the equipment of this invention follows the description in Figure 1, and modifications and adaptations may be made, provided that hospital standards are followed and it is possible to safely return the fluids aspirated from the patient (21) to the original bags (A, B or any other bag used), ensuring the proper disposal of this perfusate and biological fluids that represent a risk to health and the environment. Example 2 - Closed-loop normothermic perfusion process (recirculation)

[0064] One possible embodiment of the normothermic perfusion process can be described according to the following steps: Device preparation: a) ensure that all connections and components of the device are clean, sterilized and properly fitted; b) Check the integrity of the piercing tips (1 and 2), the protective caps of the piercing tips, flow-control clamps (3 and 4) and other elements of the equipment; c) Connect the Bag (A and B), containing the perfusate, to the piercing tips (1 and 2) of the device, which will be infused into the patient's peritoneal cavity (21); d) Adjust the flow-control clamps as needed; e) Connect the device paths to a 1 / 4" PVC Y connector (7), providing the necessary bifurcation for the process; f) From one of the branches of the Y, connect the main tube (8) (made of crystal PVC) with a length of 40 cm, which is connected to another Y connector of % (9), which connects to a tube (12) (made of crystal PVC) with a length of 100 cm, also equipped with a flow control clamp (13) in the proximal portion; which connects to the straight connector of % and this connects to the fenestrated tubular catheter (19) of 28 F that is placed in the abdominal or thoracic cavity in order to aspirate the perfusate fluid used to perform the perfusion; g) From the single part of the Y (9), connect a flexible soft tube of % (of crystal PVC) measuring 60 cm, culminating in an optional straight luer lock connector of % (17) (also of crystal PVC), through which the chemotherapeutic agent will be introduced; h) This connector is linked to an additional 100 cm tube (16); which is connected to the linear % connector that drains fluid from the peritoneal or pleural cavity through the 28F fenestrated tube (20). Start of Infusion: a) Start the chemotherapy infusion into the peritoneal cavity, using a 1 / 4" diameter crystal PVC tube (12), connected to a 28F fenestrated infusion tube (19) by a straight connector (14); b) Simultaneously, connect a second circulation tube (16) to a 28F fenestrated suction tube (20) via a straight connector (15), connected to the suction catheter (20) placed in the patient's peritoneal or pleural cavity (21); the tube (16) connects to the flexible soft tube (10) which is placed on the roller (18) of the infusion pump (11); c) The suction catheter (20) is connected to an infusion pump (11), providing safe and effective aspiration of the contents of the peritoneal cavity, which can even be reinfused into the cavity through the tube (16); Efficient fluid drainage: a) Fenestrated tubular drains (20) of 28 F are used in the patient's peritoneal cavity (21) for efficient aspiration, without risk of aspiration of intestinal loops; placed in correct positions; Controlled Recirculation: a) The aspiration catheter (20) has a Y-connection (9), connecting to an infusion system that allows for rapid and safe recirculation of the perfusate fluid or drainage to Chemotherapy Bags (A and B); b) At the end of treatment, the perfusate and the chemotherapy drug used are drained into the same bags (A and B) that contained the initial perfusate fluid.

[0065] This step-by-step guide illustrates one way to implement a perfusion process that minimizes environmental and occupational risks, further reducing the risk of spillage and contamination of the environment and professionals involved in the treatments, providing a safer and more sustainable environment.

[0066] It is known that a person skilled in the art, based on the information and examples contained in this document, may make particular embodiments of the invention not explicitly described, but which perform the same or similar functions to achieve results of the same nature. Such equivalent embodiments are encompassed by the appended claims.

Claims

CLAIMS 1. THERAPEUTIC AGENT PERFUSION DEVICE, characterized by being for closed-system perfusion, possessing tubes, valves, infusion and drainage catheters, bags, and pumps capable of inserting the perfusate into the individual to be treated and subsequently aspirating the chemical and biological fluids of the perfusate originating from the patient, human or animal, back to at least one of the original containers of the therapeutic agents, storing them in a safe place until their proper disposal in hospital waste.

2. DEVICE, according to claim 1, characterized in that it is performed at physiological (normothermic) temperature.

3. BIFURCATED THERAPEUTIC AGENT PERFUSION DEVICE, characterized by being for two-way perfusion, with closed-loop construction and having a Y-shaped bifurcated configuration (7 and 9), returning the chemical and biological fluids of the perfusate drained from the treated individual (21) back to the original containers (such as bags A and B) of the therapeutic agents, comprising the following components: a) flow monitoring device(s); b) two perfusate bags (rectangles A and B), which contain the perfusate fluid; c) two tubes (5 and 6) coupled respectively to bags A and B; d) perforators (1 and 2) at the respective proximal ends of the tubes (5 and 6); e) Y connector (7) coupled to the distal end of the tubes (5 and 6); f) flow-control clamps (3 and 4) on the tubes (5 and 6) that block the passage of liquid during perfusion; g) tube (8) that connects at its upper end the insulated portion of the first Y connector (7), to the distal part of the tube (8) and at its lower end connects to a second Y connector (9); h) soft flexible tube (10) originating from one of the bifurcated portions of this second Y connector (9), which passes through the roller (18) of the pump (11); i) the second branch of the second Y (9) is connected to a tube (12); j) a flow-cutting clamp (13) located in the tube (12), immediately after the second Y-connector (9), and at its other end it connects with a straight connector (14); k) flexible PVC fenestrated infusion tube (19) that infuses the perfusate into the patient's abdominal cavity (21); l) another fenestrated flexible PVC infusion tube (20) connected to a straight connector (15), which will spray or reinfuse the perfusate into the patient's abdominal or thoracic (pleural) cavity (21); m) PVC tube (16) that connects to the straight infusion / spray connector (15) at one end, and to the straight connector with Luer-lock (17) at the other end; n) straight connector with Luer-Lock (17) that connects to another portion of the flexible tube (10) that is inserted into the roller (18) of the pump (11), allowing control of contaminated material, medications, and bodily fluids, mitigating risks to professionals conducting medical interventions, as well as to hospital safety and the environment, representing a closed-loop bifurcated device.

4. A BIFURCED DEVICE, according to claim 3, characterized in that the perfusion is preferably normothermic.

5. BIFURCED DEVICE, according to claims 3 and 4, characterized in that it may have one or more pouches containing perfusate.

6. NORMOTHERMIC PERFUSION PROCESS, characterized by being performed with devices as defined in claims 1 and 2 or with devices as defined in claims 3 to 5, configured to be performed in a closed loop and having the following steps: preparation of the device, infusion of fluids into the patient, drainage of the infused fluids from the patient and efficient recirculation of these fluids to the original containers.

7. BIFURCED PERFUSION PROCESS, characterized by having the following steps: preparation of the device, as defined in claims 3 to 5, infusion of fluids into the patient (21), with subsequent drainage of the fluids infused into the patient (21) and efficient recirculation of these fluids to the original containers (A and B).

8. PROCESS, according to claim 7, characterized by the steps preferably following these steps: a) preparation of the device or equipment, as defined in claims 3 and 4, ensuring that all connections and components of the device are clean and sterilized; b) infusion or perfusion of the therapeutic agent (chemotherapeutic) into the patient's peritoneal cavity (21) by means of a tube connected to an infusion catheter (20); c) drainage or aspiration of fluids after waiting the appropriate treatment time for each therapy; and d) efficient recirculation of fluids to the original containers (A and B).

9. PROCESS, according to claims 7 and 8, characterized by the device preparation step having the following preferred steps: a) Ensure that all connections and components of the device are clean, sterilized, and properly fitted; b) Check the integrity of the piercing tips (1 and 2), the protective caps of the piercing tips, flow-control clamps (3 and 4) and other elements of the equipment; c) Connect the perfusate bag (A and B) containing the perfusate to the piercing tips (1 and 2) of the connector device to the bags (A and B) containing the perfusate fluid that will be infused into the patient's peritoneal cavity (21); d) Properly secure the piercing tips and adjust the flow-control clamps as needed; e) Connect the device lines to a Y-connector (7), providing the necessary bifurcation for the process; f) From one of the branches of the Y, connect the main tube (8), which is connected to another Y-connector (9), which connects to a tube (12), also equipped with a flow-control clamp (13) in the proximal portion; which connects to the straight connector (14) and this connects to the fenestrated tubular catheter (19), which is placed in the abdominal or thoracic cavity for the purpose of infusing, reinfusing, aspirating or draining the perfusate fluid used to perform the perfusion; g) From the single part of the Y (9), connect a flexible soft tube (10), culminating in a straight luerlock connector (17); h) This connector is linked to an additional tube (16), which attaches to the linear connector (15) and a catheter (20) that infuses, reinfuses, aspirates or drains fluid from the peritoneal or pleural cavity through the fenestrated tube.

10. PROCESS, according to claims 7 and 8, characterized by the infusion initiation step having the following preferred steps: a) Start the infusion of the perfusate into the peritoneal cavity, using a tube (12 or 16), connected to the fenestrated infusion or spray tube (19 or 20) by a straight connector (14 or 15); b) Simultaneously, connect a second circulation tube (12 or 16) to a fenestrated suction tube (19 or 20) by a straight connector (14 or 15), placed in the peritoneal or pleural cavity; which is connected to the flexible soft tube (10) that is placed on the roller of the perfusion pump (11); c) The suction catheter (16) is connected to a perfusion pump (11), providing safe and effective aspiration of the contents of the peritoneal cavity, which can optionally be reinfused into the cavity through the tube itself (16).

11. PROCESS, according to claims 7 and 8, characterized by the efficient drainage step of the fluids, having the preferred step of using fenestrated tubular drains (19 or 20) in the patient's peritoneal cavity (21) for efficient aspiration, without risk of aspiration of intestinal loops; placed in correct positions.

12. PROCESS, according to claims 7 and 8, characterized by the controlled recirculation step having the following preferred steps: d) The aspirating catheter (19 or 20) has a Y-connection (9), connecting to an infusion system that enables rapid and safe recirculation of the perfusate fluid or drainage to perfusate bags (A and B); e) At the end of treatment, the perfusate and the chemotherapy drug used are drained into the same bags (A and B) that contained the initial perfusate fluid.

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