# US 12,599,632 B2 · Therapeutic agent for nerve disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,599,632 B2 - Document ID: US12599632B2 - Status: Granted - Kind: B2 - Application number: 18/254,745 - Filed: 2021-11-30 - Published: 2024-02-01 - Granted: 2026-04-14 - Earliest claimed: 2020-11-30 - Assignees: Neurotech Medical Co., Ltd. - Applicants: Neurotech Medical Co., Ltd. - Inventors: Nagatoshi Kihoin; Kunihiko Okada - Web page: https://patentgrep.com/patent/US12599632B2 ## CPC - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0043: {Nose} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61P 25/00: Drugs for disorders of the nervous system - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention addresses the problem of providing a therapeutic agent that is more efficacious for treating nerve disorders, said therapeutic agent comprising a culture supernatant of mesenchymal stem cells. The present invention provides a therapeutic agent for nerve disorders, said therapeutic agent comprising a culture supernatant of mesenchymal stem cells and/or cells capable of differentiating into mesenchymal stem cells and being to be used together with stimulation of patient's nerves, wherein the stimulation is preferentially provided to one or more sites selected from the group consisting of a site of nerve damage, an area surrounding a site of nerve damage, and a site compensating for the function of a site of nerve damage. ## Claims ### Claim 1 A method of treatment for a nerve disorder of a subject in need thereof, wherein the method comprising: administering to the subject an therapeutic agent comprising a culture supernatant of a mesenchymal stem cell and/or a cell capable of differentiating into a mesenchymal stem cell, and is used in combination with stimulation of a nerve of the subject, preferentially applying the stimulation to one or more sites selected from the group consisting of a nerve injury site, an area surrounding the nerve injury site, and a site compensating for the function of the nerve injury site, and adjusting timing of applying the stimulation based on a route of administration of the therapeutic agent. ### Claim 2 (depends on 1) The method according to claim 1, wherein the stimulation is one or more kinds of stimulation selected from the group consisting of motor stimulation, sensory stimulation, electrical stimulation, magnetic stimulation, verbal stimulation, and higher brain function stimulation. ### Claim 3 (depends on 1) The method according to claim 1, wherein preferentially applying the stimulation to the one or more sites comprises applying the stimulation to the one or more sites to a greater degree relative to other sites of the subject. ### Claim 4 (depends on 1) The method according to claim 1, wherein preferentially applying the stimulation to the one or more sites comprises applying the stimulation to the one or more sites such that a blood flow rate and a metabolic rate of the one or more sites increase to a greater degree relative to other sites of the subject. ### Claim 5 A method of treatment for a nerve disorder of a subject in need thereof, wherein the method comprising: nasally administering to the subject an therapeutic agent comprising a culture supernatant of a mesenchymal stem cell and/or a cell capable of differentiating into a mesenchymal stem cell, and is used in combination with stimulation of a nerve of the subject, and the stimulation is performed between before and 16 hours after administration of the therapeutic agent. ### Claim 6 (depends on 5) The method according to claim 5, wherein the stimulation is one or more kinds of stimulation selected from the group consisting of motor stimulation, sensory stimulation, electrical stimulation, magnetic stimulation, verbal stimulation, and higher brain function stimulation. ### Claim 7 (depends on 5) The method according to claim 5, wherein the culture supernatant is not diluted or concentrated in terms of soluble solid content. ### Claim 8 (depends on 5) The method according to claim 5, wherein a lyophilizate of the culture supernatant is dissolved and then used at the time of administration. ### Claim 9 A method of treatment for a nerve disorder of a subject in need thereof, wherein the method comprising: intravenously administering to the subject an therapeutic agent comprising a culture supernatant of a mesenchymal stem cell and/or a cell capable of differentiating into a mesenchymal stem cell, and is used in combination with stimulation of a nerve of the subject, and the stimulation is performed between before and 3 hours after administration of the therapeutic agent. ### Claim 10 (depends on 9) The method according to claim 9, wherein the stimulation is one or more kinds of stimulation selected from the group consisting of motor stimulation, sensory stimulation, electrical stimulation, magnetic stimulation, verbal stimulation, and higher brain function stimulation. ### Claim 11 (depends on 9) The method according to claim 9, wherein the culture supernatant is not diluted or concentrated in terms of soluble solid content. ### Claim 12 (depends on 9) The method according to claim 9, wherein a lyophilizate of the culture supernatant is dissolved and then used at the time of administration. ### Claim 13 A method of treatment for a nerve disorder of a subject in need thereof, wherein the method comprising: subcutaneously administering to the subject an therapeutic agent comprising a culture supernatant of a mesenchymal stem cell and/or a cell capable of differentiating into a mesenchymal stem cell, and is used in combination with stimulation of a nerve of the subject, and the stimulation is performed between before and 16 hours after administration of the therapeutic agent. ### Claim 14 (depends on 13) The method according to claim 13, wherein the stimulation is one or more kinds of stimulation selected from the group consisting of motor stimulation, sensory stimulation, electrical stimulation, magnetic stimulation, verbal stimulation, and higher brain function stimulation. ### Claim 15 (depends on 13) The method according to claim 13, wherein the culture supernatant is not diluted or concentrated in terms of soluble solid content. ### Claim 16 (depends on 13) The method according to claim 13, wherein a lyophilizate of the culture supernatant is dissolved and then used at the time of administration. ### Claim 17 A method of treatment for a nerve disorder of a subject in need thereof, wherein the method comprising: administering to the subject an therapeutic agent comprising a culture supernatant of a mesenchymal stem cell and/or a cell capable of differentiating into a mesenchymal stem cell, and is used in combination with stimulation of a nerve of the subject, and the stimulation is preferentially applied to one or more sites selected from the group consisting of a nerve injury site, an area surrounding the nerve injury site, and a site compensating for the function of the nerve injury site, wherein the culture supernatant is not diluted or concentrated in terms of soluble solid content. ### Claim 18 A method of treatment for a nerve disorder of a subject in need thereof, wherein the method comprising: administering to the subject an therapeutic agent comprising a culture supernatant of a mesenchymal stem cell and/or a cell capable of differentiating into a mesenchymal stem cell, and is used in combination with stimulation of a nerve of the subject, and the stimulation is preferentially applied to one or more sites selected from the group consisting of a nerve injury site, an area surrounding the nerve injury site, and a site compensating for the function of the nerve injury site, wherein a lyophilizate of the culture supernatant is dissolved and then used at the time of administration.