The response rate of systemic chemotherapy for metastatic lymph nodes is low. This invention presents the optimal values for solvent properties, especially viscosity, in a method for directly administering drugs to lymph nodes (lymphatic drug delivery system). In 2024, a specified clinical study (jRCTs021230040) on lymph node metastasis was started at the Iwate Medical University Hospital Head and Neck Cancer Center.

In systemic chemotherapy for metastatic lymph nodes, the amount of drug delivered to the metastatic lymph nodes is small. This is due to the increase in internal pressure caused by tumor growth in the lymph nodes and the disappearance of microvessels caused by the formation of tumor mass. In this invention, we clarified the optimal viscosity range of the solvent for the lymphatic drug delivery system, which directly administers drugs to lymph nodes.

• The amount of anticancer drug required to treat one metastatic lymph node is 1/100 to 1/1000 of the systemic dose.
• The drug can be administered into the lymph node under ultrasound guidance.
• An international patent has been filed for the solvent of the administered drug.

1. Treatment and prophylactic therapy of affiliated lymph nodes in head and neck cancer, breast cancer, etc.
2. Pharmaceutical companies aiming to develop drugs by drug repositioning and generics
3. Medical device manufacturers aiming to develop a dosing system

• Using positron emission tomography (PET), we can measure the regional metabolism, perfusion and signal transmission between neurotransmitters and receptors in various organ systems of living humans and animals, such as the brain and heart. Recent technical developments have shown that the mind, or at least some parts of it, can be demonstrated by "imaging".

Our group has had considerable achievements in clinical research on drug effects and side effects, elucidation of underlying mechanism of alternative and complementary therapies, as well as exercise physiology.

• Medical devices and healthcare devices which have several functions with small size have been developed using precise micromachining technology and MEMS (Microelectromechanical systems) technology. More precise and safe diagnostics and therapy, as well as novel diagnostics and treatment can be realized by developing high-functionalized endoscopes and catheters and developing novel medical devices. Healthcare without restriction of location and time is aimed by developing thin, light and high-functionalized new healthcare devices.

Besides of basic research, we are working in cooperation with clinicians and medical device companies for practical use. We founded a university-launched venture company for bridge-building between university and company and collaborative researches have been performed.

• Dr. Katsunori Nonogaki has developed the novel ultrasound irradiation device, which can improve the autonomic nervous system activity and peripheral circulation. In addition, the ultrasoud device can improve hypertension and hyperglycemia within 20 min in subjects with drug-resistant hypertension and diabetes. Our initial device was approved in Japan (226AIBZX00028000). This device will be avaliable for the treatment of 1) muscle pain, 2) the autonomic neural dysfunction and stress-related disorders, 3) hypertention, and 4) diabetes. Moreover, the device will be usefull for your healthy life and aging care.

Our aims are to export the device internationally. We seek the investment and international business partners.

• Metabolic syndrome is an important view point, when we consider the preventive medicine. Hypertension is one of the most important points to prevent the cardiovascular events. However, there is no method to measure the baroreflex sensitivity of the artery in the patients with hypertension. Tohoku University had invented the new method to evaluate the baroreflex sensitivity of the heart and artery (JP Patent No.4789203).

By the use of this machine, the baroreflex sensitivity of an artery in the patients can easily be measured noninvasively. It enables to predict the occurrence of hypertension and evaluate the therapy of hypertension easily, while allowing prevention of the cardiovascular events.

• Complexity of the cardiac contraction sequence is still not fully understood because the dynamic mechanical excitation process, which directly correlates with contraction, cannot be accurately measured by CT, MRI, SPECT, or conventional ultrasound. By developing a noninvasive novel imaging modality with high temporal and spatial resolutions (US patent 5840028), we have detected the minute mechanical response (velocity component) to the propagation of the action potential in the human heart or to detect the propagation of the vibrations along the heart wall caused by the valve closure (Fig. 2).
• By applying the same procedure to the human arteries, the regional change in wall thickness caused during one cardiac cycle can be measured with high spatial resolution (Fig. 1). From the measurement, the regional elasticity of tissue surrounding atherosclerotic plaque can be determined. By comparing the pathological findings with the distribution of elasticity, elasticity of lipid and that of fibrous tissue were determined. Thus, each point inside the plaque is classified into lipid or fibrous tissue using transcutaneous ultrasound (Fig. 3).

This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with high spatial resolution.
We are prepared to provide academic consultations to companies interested in our research.

Amyotrophic lateral sclerosis (ALS) is a representative intractable neurodegenerative disease, and the development of effective therapies is desired. A novel phase I trial of intrathecal administration of recombinant HGF protein was conducted at Tohoku University Hospital. Based on the results, a phase II trial (investigator-initiated clinical trial) to confirm efficacy and safety for ALS was conducted and completed at the Tohoku and Osaka University Hospital from 2016 to 2022. Although there was no statistically significant difference in the primary endpoint, additional analyses are currently ongoing. Clinical development of the same formulation for acute spinal cord injury is also underway.

Simultaneous development of a novel intrathecal formulation of recombinant HGF protein, and a medical device (a subcutaneous port with an intrathecal catheter) that enable repeated intrathecal administration for efficient and selective delivery to the central nervous system.

• We developed a novel rat model of ALS model (Nagai M, et al. 2001)
• Intrathecal continuous administration of HGF protein was confirmed to have a slowing effect on progression in this model
• Phase I and II clinical trials have been completed, and the efficacy is currently being verified through additional analysis

We have been working with Kringle Pharma, Inc., Keio University (Prof. Hideyuki Okano and Prof. Masaya Nakamura), and Asahikawa Medical University (Prof. Hiroshi Funakoshi) to develop this drug. Phase I and II clinical trials for ALS have been completed. In addition, a phase III clinical trial for acute spinal cord injury is near completion. Additional collaboration with pharmaceutical companies is planned.

Amyotrophic lateral sclerosis (ALS) is a representative intractable neurodegenerative disease, and the development of effective therapies is desired. A novel phase I trial of intrathecal administration of recombinant HGF protein was conducted at Tohoku University Hospital. Based on the results, a phase II trial (investigator-initiated clinical trial) to confirm efficacy and safety for ALS was conducted and completed at the Tohoku and Osaka University Hospital from 2016 to 2022. Although there was no statistically significant difference in the primary endpoint, additional analyses are currently ongoing. Clinical development of the same formulation for acute spinal cord injury is also underway.

Simultaneous development of a novel intrathecal formulation of recombinant HGF protein, and a medical device (a subcutaneous port with an intrathecal catheter) that enable repeated intrathecal administration for efficient and selective delivery to the central nervous system.

• We developed a novel rat model of ALS model (Nagai M, et al. 2001)
• Intrathecal continuous administration of HGF protein was confirmed to have a slowing effect on progression in this model
• Phase I and II clinical trials have been completed, and the efficacy is currently being verified through additional analysis

We have been working with Kringle Pharma, Inc., Keio University (Prof. Hideyuki Okano and Prof. Masaya Nakamura), and Asahikawa Medical University (Prof. Hiroshi Funakoshi) to develop this drug. Phase I and II clinical trials for ALS have been completed. In addition, a phase III clinical trial for acute spinal cord injury is near completion. Additional collaboration with pharmaceutical companies is planned.