JPWO2019209943A5

JPWO2019209943A5 -

Info

Publication number: JPWO2019209943A5
Application number: JP2021509954A
Authority: JP
Publication date: 2022-04-28

Claims

A dosage form containing magnesium threonic acid for the treatment of diseases, disorders, syndromes and / or conditions in patients in need thereof.
(A) At least a portion of the magnesium (Mg) and threonic acid (T) of the magnesium threonic acid is present in the salt form of MgT ₂ ;
(B) The magnesium threonic acid is present in an amount of about 200-6000 mg;
(C) When administered to a patient in need thereof, the dosage form is sufficient to provide an in vivo plasma profile of threonic acid containing an average _Cavg of about 5 μg / mL to about 20 μg / mL. , Dosage form.

The in vivo plasma profile from the dosage form is
(I) Show a coefficient of variation that is less than about 170% and / or
(Ii) show an average T _max for at least about 4.5 hours,
The dosage form according to claim 1.

Dosage form containing magnesium threonic acid
(A) At least a portion of the magnesium (Mg) and threonic acid (T) of the magnesium threonic acid is present in the salt form of MgT ₂ ; and
(B) The magnesium threonic acid is present in an amount of about 200-6000 mg; and (c 1 ) the in vivo plasma profile from the dosage form shows a coefficient of variation of less than about 170% , or
(C2) The in vivo plasma profile from the dosage form exhibits a skewness of less than about 0.2, or
(C3) The release of the magnesium threonic acid from the dosage form is about 0.2 h ^-1 calculated from measurements obtained using a USP type II (paddle) dissolution system at 75 rpm at a temperature of about 37 ° C. ~ 0.6h ^-1 shows the primary emission constant;
Dosage form.

The primary emission constant is
(I) Approximately 0.25h ^-1 to 0.45h ^-1 or
(Ii) Approximately 0.3h ^-1 to 0.4h ^-1 ,
The dosage form according to claim 3 .

The dosage form according to any one of claims 1 to 4 , which is orally administered to the patient and / or is administered to the patient in a satiety state .

(I) Sufficient to provide at least about 15 mg / kg lean body mass / dose of magnesium threonic acid given every 12 hours in patients in need of treatment for diseases, disorders, syndromes and / or conditions. There and
(Ii) Sufficient to provide about 10-30 mg / kg lean body mass / dose of magnesium threonic acid given every 12 hours in patients in need of treatment for diseases, disorders, syndromes and / or conditions. And,
(Iii) Sufficient to provide at least about 15 mg / kg lean body mass / dose / day of magnesium threonic acid in patients in need of treatment for diseases, disorders, syndromes and / or conditions, and.
(Iv) Sufficient to provide about 20-60 mg / kg lean body mass / day of magnesium threonic acid, and.
(V) Sufficient to provide at least about 30 mg / kg lean body mass / day of magnesium threonic acid.
At least one of
The dosage form according to any one of claims 1 to 5 .

The magnesium threonic acid is
(I) Existing or present in an amount of about 40-about 77% wt / wt
(Ii) Exist in or at an amount of about 45-about 70% wt / wt
(Iii) Present in an amount of about 70% or
(Iv) present in an amount of about 53%,
The dosage form according to any one of claims 1 to 6 .

Including more carnauba wax ,
The carnauba wax is present in an amount of about 10 to about 30% wt / wt.
In particular, the carnauba wax is present in an amount of about 10% wt / wt, or the carnauba wax is present in an amount of about 28% wt / wt.
The dosage form according to any one of claims 1 to 7 .

Further containing magnesium stearate,
The magnesium stearate is present in an amount of about 1% to about 3% wt / wt.
In particular, the magnesium stearate is present in an amount of about 1% to about 2% wt / wt.
More particularly, the magnesium stearate is present in an amount of about 1.4% wt / wt, or the magnesium stearate is present in an amount of about 2% wt / wt.
The dosage form according to any one of claims 1 to 8 .

The dosage form according to claim 9 , wherein the weight ratio of the carnauba wax to the magnesium stearate is larger than about 12 or about 20 .

(A) The weight ratio of the carnauba wax to the magnesium stearate in the inner portion including the inner portion and the outer portion is about 5 to about 12, and in particular, about 8 or more. , About 10 or
(B) Liquid, semi-liquid, semi-solid or solid, or
(C) Gels, pills, tablets, capsules, beads, emulsions, granules, pastes, granules, powders, syrups, suspensions, slurries or aerosols.
The dosage form according to any one of claims 1 to 10 .

Contains more additional substances ,
The additional substance is a pharmaceutically acceptable excipient and
In particular, the pharmaceutically acceptable excipient is selected from the group consisting of binders, bulking agents, lubricants, solubilizers and any combination thereof, in which case.
The pharmaceutically acceptable excipients include lactose, crystalline cellulose, silicon dioxide, titanium dioxide, stearic acid, starch, sodium starch glycolate, povidone, pregelatinized starch, croscarmellose, ethyl cellulose, dicalcium phosphate, and the like. Selected from the group consisting of talc, starch, calcium stearate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, shelac, hardened vegetable oil, honeydew and any combination thereof.
The dosage form according to any one of claims 1 to 11 .

The dosage form according to any one of claims 1 to 12 , which is used in a method for treating a disease, disorder, syndrome and / or condition in a patient in need thereof.
The method comprises orally administering the dosage form, in which case.
The dosage form is sufficient to provide a lean body mass / dose of at least about 15 mg / kg of MgT ₂ to a patient with a disease, disorder, syndrome and / or condition.
In particular, the above method
(A) To determine the physiological concentration of threonic acid in the patient prior to administration of the dosage form;
(B) To determine at least one additional physiological concentration of threonic acid in the patient after oral administration of the dosage form.
Including
The physiological concentration is in serum concentration, plasma concentration, urine concentration or cerebrospinal fluid concentration.
In particular, the dosage form is administered with food twice daily.
Dosage form .

The patients are cardiovascular disease, neurodegenerative disorder, sleep disorder, neurological disorder, nerve injury, developmental disorder / autism spectrum disorder, autoimmune disease, hereditary disorder, rheumatic disease, inflammatory disease, neuropsychiatric disorder. Suffering from a disease, disorder, syndrome and / or condition selected from cancer, habits and trauma ,
The diseases, disorders, syndromes and / or conditions include mild cognitive dysfunction, short-term memory loss, long-term memory loss, Alzheimer's disease, Parkinson's disease, Huntington's disease, autism, schizophrenia, cognitive decline, depression, dementia. , Attention Defect Hyperactivity Disorder (ADHD), Muscle Atrophic Lateral Sclerosis (ALS), Polysclerosis (MS), Diabetes, Cardiovascular Disease, Hypertension, Migraine, Glaucoma, Mood Disorder, Stress, Anxiety , Depression, sleep disorders, psychiatric disorders, metabolic disorders, fatigue, cancer, HIV, hepatitis, spinal cord injury, postoperative recovery, post-traumatic stress disorders, arthritis, neuropathy pain, inflammation, tremor and fibromyalgia ,
The dosage form according to claim 13 .

The method for producing the dosage form according to any one of claims 1 to 13 .
(A) To form a mixture containing the magnesium thoreonate and additional substances, at least a portion of the magnesium (Mg) and threonic acid (T) of the magnesium threonic acid is present in the salt form of MgT ₂ . To do, to form;
(B) A method comprising prescribing the mixture to form the dosage form.