# US 11,433,038 B2 · High concentration medicant solutions for treating neurological disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,433,038 B2 - Document ID: US11433038B2 - Status: Granted - Kind: B2 - Application number: 16/850,859 - Filed: 2020-04-16 - Published: 2020-10-22 - Granted: 2022-09-06 - Earliest claimed: 2017-10-23 - Assignees: Cerebral Therapeutics, Inc.; The Regents of the University of Colorado - Applicants: Cerebral Therapeutics, Inc. - Inventors: Daniel J. Abrams; Thomas Joseph Anchordoquy - Web page: https://patentgrep.com/patent/US11433038B2 ## CPC - A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) - 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 9/0085: {Brain, e.g. brain implants; Spinal cord} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61P 25/08: Antiepileptics; Anticonvulsants - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - A61P 25/24: Antidepressants - 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 Highly concentrated solutions are disclosed along with methods of inhibiting and/or ameliorating functional neurological disorders of the brain. The method may include administering directly to a brain of a subject a medicament multiple times over a time period of at least two days. The medicament may include a half-life of less than 2 hour in the cerebrospinal fluid. The method may include inhibiting and/or ameliorating a functional neurological disorder of the brain using the medicant. ## Claims ### Claim 1 A method of ameliorating a symptom of epilepsy in a subject, comprising: administering directly to the brain of a subject a medicament for ameliorating the symptom of epilepsy over a time period of at least two days, wherein the medicament exhibits a half-life of less than 2 hours in cerebrospinal fluid and wherein the administered medicament has a concentration from 100 mg/mL to 500 mg/mL; determining medicament concentration by sampling blood serum and performing a test of medicament concentration in the sampled blood serum; and changing daily flow rate and/or concentration of the administered medicament based on the medicament concentration in the sampled blood serum to achieve a concentration in the blood serum of between about 1 microgram/mL to 500 microgram/mL, wherein the medicament comprises valproic acid or a pharmaceutically active derivative thereof. ### Claim 2 (depends on 1) The method of claim 1, wherein during treatment the medicament has a concentration in the blood serum of between 2 μg/ml to 200 μg/ml; and wherein the medicament is substantially continuously administered directly to cerebrospinal fluid of the subject's brain via a catheter. ### Claim 3 (depends on 1) The method of claim 1, wherein the administering directly to the brain of the subject comprises administering is via multiple bolus pulses of the medicament. ### Claim 4 (depends on 3) The method of claim 3, wherein administering directly to the brain of the subject is in multiple bolus pulses of the medicament during treatment, and wherein a dosage is based upon a target treatment dosage of the medicament and the medicament's half-life in the blood serum such that the target treatment dosage during a treatment period is multiplied by a number of half-lives lost occurring during gaps in a treatment period to achieve meaningful target therapeutic levels. ### Claim 5 (depends on 1) The method of claim 1, wherein there is a substantially linear relationship between a concentration of the medicament in the blood serum and a daily dosage of the medicament. ### Claim 6 (depends on 1) The method of claim 1, further comprising: monitoring administration of the medicament by monitoring the subject's perception of their own body temperature. ### Claim 7 (depends on 1) The method of claim 1, wherein the medicament is administered as part of a pharmaceutical composition comprising citric acid, an acetate, and a phosphate. ### Claim 8 (depends on 1) The method of claim 1, wherein the medicament is only administered to one lateral brain ventricle on one side of the brain and not bilaterally administered to both ventricles. ### Claim 9 A method of ameliorating a symptom of epilepsy, comprising: administering a medicament with a catheter directly to the brain of a subject, wherein the medicament comprises a half-life of less than 2 hours in cerebrospinal fluid and wherein the administered medicament has a concentration from 100 mg/mL to 500 mg/mL; determining medicament concentration by sampling blood serum and performing a test of the concentration of medicament in the sampled blood serum; and changing daily flow rate and/or concentration of the administered medicament based on the concentration of the medicament in the sampled blood serum to achieve a concentration in the blood serum of between about 1 microgram/mL to 500 microgram/mL, wherein the medicament ameliorates and/or modifies the epilepsy, wherein the medicament comprises valproic acid or a pharmaceutically active derivative thereof. ### Claim 10 (depends on 9) The method of claim 9 wherein the medicament has an aqueous solubility of at least of 50 mg/mL. ### Claim 11 (depends on 10) The method of claim 10, wherein the medicament is in a formulation with a composition, comprising citric acid, an acetate, and a phosphate. ### Claim 12 (depends on 11) The method of claim 11, wherein the medicament has a solubility of at least of 100 mg/mL in the formulation. ### Claim 13 (depends on 11) The method of claim 11, wherein the medicament has a solubility of at least of 150 mg/ml in the formulation. ### Claim 14 (depends on 11) The method of claim 11, wherein the medicament has a solubility of at least of 200 mg/ml in the formulation. ### Claim 15 (depends on 11) The method of claim 11, wherein the medicament has a solubility of at least of 300 mg/ml in the formulation. ### Claim 16 A method of ameliorating seizures of a patient diagnosed with epilepsy, comprising: administering directly to cerebrospinal fluid of a patient's brain a formulation comprised of valproic acid or a pharmaceutically acceptable salt thereof, wherein the valproic acid of the pharmaceutically acceptable salt thereof has a half-life of less than 2 hours in cerebrospinal fluid and has a concentration in the formulation from 100 mg/mL to 500 mg/mL; continuing the administration directly to cerebrospinal fluid of the patient's brain over a period of days; determining a concentration of the valproic acid or the pharmaceutically acceptable salt thereof by sampling blood serum and performing a test of the concentration of the valproic acid or the pharmaceutically acceptable salt thereof in the sampled blood serum; and changing daily flow rate and/or concentration of the administered formulation based on the concentration of the valproic acid or the pharmaceutically acceptable salt thereof in the sampled blood serum to achieve a concentration in the blood serum of between about 1 microgram/mL to 500 microgram/mL.