Unlock instant, AI-driven research and patent intelligence for your innovation.

Sustained release injectable neurosteroid formulations

A steroid, neurological technology, applied in nervous system diseases, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of low water solubility, limited preparation options, etc.

Inactive Publication Date: 2019-11-29
MARINUS PHARMA
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These compounds are characterized by very low water solubility, which limits their formulation options

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Sustained release injectable neurosteroid formulations
  • Sustained release injectable neurosteroid formulations
  • Sustained release injectable neurosteroid formulations

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0129] The present disclosure also provides methods of treating CNS disorders or conditions including anxiety, generalized anxiety disorder, social anxiety disorder, panic disorder, anxiety or agitation due to Alzheimer's dementia, schizophrenia, substance withdrawal syndrome symptoms (alcohol, benzodiazepines barbiturates and cocaine), post traumatic stress disorder (PTSD), tremor, essential tremor, spasticity due to cerebral palsy, depression (including major depression, major depressive disorder, major depression, single depression, unipolar disorder, or recurrent depression), postpartum or postpartum depression, atypical depression, melancholic depression, psychotic major depression (PMD), catatonic depression, seasonal affective disorder (SAD), dysthymia, bipolar Depression, depressive personality disorder (DPD), recurrent transient depression (RBD), mild depressive disorder, bipolar or manic depressive disorder, posttraumatic stress disorder, postmenopausal depression, ...

specific Embodiment approach 1

[0141] Specific embodiments 1. A sustained release injectable neurosteroid formulation comprising neurosteroid particles with a D50 of less than 10 microns, said neurosteroid particles comprising:

[0142] a) a neurosteroid of formula I or a pharmaceutically acceptable salt thereof:

[0143] in:

[0144] is a double bond or a single bond;

[0145] X is O, S or NR 11 ;

[0146] R 1 is hydrogen, hydroxy, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted Substituted aryl, or optionally substituted arylalkyl;

[0147] R 4 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted (cycloalkyl)alkyl, or -OR 40 , where R 40 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted (cycloalkyl)alkyl, or optionally substituted C 3 -C 6 carbon ring;

[0148] R 4a is hydro...

specific Embodiment approach 8

[0170] Embodiment 8. The formulation of any one of embodiments 1 to 6, further comprising one or more of the following:

[0171] (a) 0.5% to 1.5% sodium chloride (percentage by weight);

[0172] (b) buffering agents;

[0173] (c) preservatives, wherein the preservatives are benzyl alcohol, chlorobutanol, 2-ethoxyethanol, parabens (including methyl, ethyl, propyl, butyl, and combinations), Benzoic acid, sorbic acid, chlorhexidine, phenol, 3-cresol, thimerosal, phenylmercury salts, or mixtures of any of the foregoing.

[0174] Embodiment 9. The formulation of embodiment 1, wherein:

[0175] The neurosteroid is ganaxolone or prepregnanolone;

[0176] The at least one surface stabilizer is a polymer surface stabilizer selected from hydroxyethyl starch, dextran, povidone, and a mixture of any of the foregoing, wherein the neurosteroid and the polymer surface stabilizer ( wt:wt) in a ratio of about 4:1 to about 0.2:1; and the formulation comprises an additional surface stabilize...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
sizeaaaaaaaaaa
sizeaaaaaaaaaa
sizeaaaaaaaaaa
Login to View More

Abstract

The disclosure provides a sustained release injectable neurosteroid formulation comprising neurosteroid particles having a D50 of less than 10 microns, the neurosteroid particles comprising a neurosteroid of Formula I: Formula I or a pharmaceutically acceptable salt thereof, wherein: is a double or single bond and the variables, e.g., R1,R2, R3, R4, R4a, R5, R6, R7, R8, R9, R10, and R10a are described herein. The formulation comprises neurosteroid particles comprising the neurosteroid and a polymeric surface stabilizer and provides an effective plasma concentration of the neurosteroid at steady state for at least 48 hours, and in some embodiments for at least 4 weeks. The sustained release injectable neurosteroid formulation can formulated for intramuscular or subcutaneous administration.The disclosure provides a method of treating a patient having seizures, anxiety, agitation, depression (including post-partum depression), schizophrenia, post-traumatic stress disorder, or tremors byadministering the sustained release neurosteroid formulation to the patient. In certain embodiments the neurosteroid is ganaxolone.

Description

Background technique [0001] Pregnane neurosteroids are a class of compounds useful as anesthetics, sedatives, hypnotics, anxiolytics and anticonvulsants. These compounds are characterized by very low water solubility, which limits their formulation options. Long-acting, sustained release injectable formulations of pregnane neurosteroids are particularly desirable because these compounds may be used in clinical indications where treatment is best done in an outpatient setting but where stable blood levels of the compound are particularly desired. These disorders include seizure disorders, depression (including postpartum depression), and psychiatric disorders. [0002] There are no extended-release injectable neurosteroid preparations. Accordingly, there is a need for sustained release injectable neurosteroid formulations for the treatment of CNS disorders including seizure disorders, anxiety, depression and pain. The present disclosure fulfills this need, and provides addit...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/57A61K9/00A61K47/10A61K47/36A61K9/10A61K9/14A61P25/24A61P25/14A61P25/22A61P25/18
CPCA61K47/10A61K47/36A61K9/10A61P25/24A61P25/14A61P25/22A61P25/18A61K9/146A61K31/57A61K9/0019A61K9/145A61K47/26A61K31/58
Inventor 迈克尔·萨波里托张明宝雷蒙德·C·格洛瓦基大卫·采卡伊
Owner MARINUS PHARMA