Two-component formulations, methods and procedures to prevent or reduce trauma-induced neuropathology and neurodegeneration

A method for one or more of preventing, reducing the effects of, or reducing the risk of development of, neuropathology incident to trauma, the method comprising the steps or actions of

• A. providing a formulation adapted for the prevention of the development of neuropathology, wherein the formulation comprises two biologically active compounds in amounts that are pharmaceutically effective for each compound, respectively, when administered in combination with the other biologically active compound, the two compounds respectively comprising a formulation comprising a pharmaceutically effective amount of:
• i. at least one biologically active compound from the group comprising anticonvulsants and antiepileptic drugs, wherein the anticonvulsant or antiepileptic is at east one form of gabapentin;
• and
• ii. at least one biologically active compound from the group comprising neurosteroids and neuroactive steroids, wherein the neurosteroid or neuroactive steroid is at least one form of progesterone or synthetic progestin;
• wherein the formulation is in a form adapted and arranged for administration to a mammal in need thereof, such that the development, or the risk of development, of neuropathology is reduced, lessened, attenuated or prevented, and
• B. administering the formulation to a mammal in need thereof.

A pharmaceutical formulation adapted for the prevention of the development of neuropathology incident to traumatic brain injury, or for the amelioration of the effects caused by traumatic brain injury to a subject,

• the formulation comprising two biologically active compounds in amounts that are pharmaceutically effective for each compound, respectively, when administered in combination with the other biologically active compound, the formulation comprising a pharmaceutically effective amount of:
• A) at least one biologically active compound selected from the group consisting of anticonvulsants and antiepileptics,
• wherein the at least one anticonvulsants and antiepileptics are one or more compounds selected from the group consisting of gabapentin, pregabalin, barbiturates, benzodiazepines, bromides, carbamates, carboxamides, fatty acids, fructose derivatives, hydantoins, oxazolidinediones, propionates, pyrimidinediones, pyrrolidines, succinimides, sulphonamides, triazines, ureas and valproyamides;
• and
• B) at least one biologically active compound selected from the group consisting of neurosteroids and neuroactive steroids,
• wherein the at least one neurosteroids and neuroactive steroids are one or more compounds selected from the group consisting of progesterone, progesterone prodrugs, other progesterone compounds selected from medroxyprogesterone acetate, megestrol acetate, 17alpha-hydroxyprogesterone, 5alpha-dihydroxyprogesterone, 3alpha,5alpha-trihydroxyprogesterone, 14b-hydroxy progesterone, 17alpha-hydroxyprogesterone caproate, 16-methyl-17-benzoyloxypregnen-4-en-3,20-dione, hydroxyprogesterone-3-O-carboxymethyloxime, 21-succinyloxy-6,19-epoxyprogesterone, 6,19-oxidoprogesterone, 17-p-bromophenylcarbamoyloxypregn-4-ene-3,20-dione, 17-phenylcarbamoyl-oxypregn-4-ene-3,20-dione, 4-pregnene-3,20-dione, 6,19-methanoprogesterone, 16,17-cyclohexano-4,5-dihydroprogesterone, nepapakistamine, vaganine D, Crinone, 18-oxo-18-vinylprogesterone, 16,17-cyclopropanoprogesterone, caproxyprogesterone, 21-hydroxy-6,19-oxidoprogesterone, 17-acetoxy-9-fluoro-6-methylprogesterone, ZK 136798, 3,17-dihydroxy-7-(4-methoxyphenyl)-androst-5-ene, 3,17-diacetate, progesterone-11HS-horseradish peroxidase, 21-hydroxy-11,19-oxidopregn-4-ene-3,20-dione, 21-hydroxy-6,19-oxidopregn-4-ene-3,20-dione, 4-cyanoprogesterone, 11,19-oxidoprogesterone, 6-fluoroprogesterone, 2-hydroxy-4-pregnene-3,20-dione, progesterone-3-(0-carboxymethyl oxime)-horseradish peroxidase, progesterone-11-hemisuccinyl-bovine serum albumin, pentarane B, pentarane A, progesterone 6-hemimaleate, progesterone 6-hemisuccinate, 7-(carboxyethylthio)progesterone, progesterone 3-(O-carboxymethyl)oxime-bovine serum albumin, 18-ethynylprogesterone, 18-vinylprogesterone, 6-methylprogesteron-17-pivalate, progesterone-11-bovine serum albumin, allylestriol, progesterone-3-ethanolimine, 3,20-dioxopregn-4-ene-18′-carboxaldehyde cyclic 18′-(1,2-ethandiylmercaptal), 18-ethylenedithioprogesterone, 17-acetoxy-6,16-dimethylene-4-pregnene-3,20-dione, 17-hydroxy-6-dehydroprogesterone, 2′-methyl-16,17-cyclohexaneprogesterone, 21,21-dichloroprogesterone, hydroxyprogesterone hemisuccinate bovine serum albumin tetramethylrhodamine isothiocyanate, 11-progesteryl-2-carboxymethyltyramine-4-(10-methyl)acridinium-9-carboxylate, progesterone 12-succinyltyrosine methyl ester, progesterone 11-succinyltyrosine methyl ester, 11-progesteryl-2-succinoyltyramine-4-(10-methyl)acridinium-9-carboxylate, 2-hydroxymethyleneprogesterone, 2-cyanoprogesterone, 17-(phenylseleno)progesterone and 21-(phenylseleno)progesterone, neuroactive progestagens, neuroactive androgens (including but not limited to androstenedione (the precursor of 3alpha,5alpha-A, or androsterone), androsterone (5alpha-androstan-3alpha-ol-17-one;
• 3alpha,5alpha-A), 5alpha-dihydrotestosterone (5alpha-DHT) and its metabolite 5alpha-androstane-3alpha,17beta-diol (3alpha,5alpha-Adiol), 3α,17β-dihydroxy-5α-androstane, 3α-hydroxy-5α-androstan-17-one, 3α-hydroxy-5β-androstan-17-one, androst-5-ene-3β,17β-diol, 3β,17α-dihydroxy-pregn-5-en-20-one (17α-hydroxy-pregnenolone), 3β-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione)), neuroactive estrogens, neuroactive glucocorticoids, allopregnanolone, allotetrahydrodeoxycorticosterone (THDOC), and dehydroepiandrosterone (DHEA), estradiol benzoate, methylprednisolone, alphaxalone, alphadolone, hydroxydone, minaxolone, ganaxolone, deoxycorticosterone, 3 alpha-hydroxy-5-alpha-pregnan-one (allopregnanolone), 3 alpha,21-dihydroxy-5 alpha-and pregnan-20-one (allotetrahydro), and
• wherein the formulation is in a form and a dosage with respect to each of its components such that it is adapted and arranged for administration to a mammal in need thereof, such that the development, or the risk of development, of neuropathology incident to traumatic brain injury is reduced, lessened, attenuated or prevented.