Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Implantable polymeric device for sustained release of dopamine agonist

a polymeric device and agonist technology, applied in the direction of prosthesis, drug composition, powder delivery, etc., can solve the problems of inconvenient administration, abnormalities, and technical difficulties

Inactive Publication Date: 2005-02-10
TITAN PHARMA
View PDF36 Cites 90 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

FIG. 1 depicts in vitro release of apomorphine over time. FIG. 1 shows the average cumulative release of apomorphine HCl (“ApoH”) from implants loaded with 50%, 60%, or 70% ApoH and washed for 30 minutes (FIG. 1A), 60 minutes (FIG. 1B), or 120 minutes (FIG. 1C) in ethanol.
FIG. 2 depicts in vitro release of ApoH and loratidine (“LA”) over time from an implant loaded with 49% ApoH and 21% LA.

Problems solved by technology

Often, after several years of treatment with levodopa, abnormalities emerge, including involuntary movements during the “on” phase of clinical improvement and re-emergence of Parkinson's-type symptoms during “off” phases.
These means of administration are inconvenient, in the case of subcutaneous injection, and technically difficult, in the case of pump administration, especially for Parkinson's patients whose dexterity is impaired due to the disease itself and the movements associated with chronic levodopa treatment.
None of these methods permits continuous administration over long periods of time.

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
  • Implantable polymeric device for sustained release of dopamine agonist
  • Implantable polymeric device for sustained release of dopamine agonist

Examples

Experimental program
Comparison scheme
Effect test

example 1

Materials and Methods

Materials

The following materials were used: Apomorphine HCl, supplied by Hawkins, Inc. Triamcinolone Acetonide, supplied by Spectrum Glutathione, supplied by Aldrich, St. Louis, Mo. Ethylene vinyl acetate copolymer, 33% vinyl acetate, supplied by Southwest Research Institute, San Antonio, Tex. Methanol, ChromAR HPLC Grade, supplied by Mallinckrodt, St. Louis, Mo. Acetonitrile, ChromAR HPLC Grade, supplied by Mallinckrodt, St. Louis, Mo. Trifluoro Acetic Acid, 99%, Spectrochemical grade, supplied by Aldrich Chemicals, St. Louis, Mo. Sodium Dodecyl Sulfate, 99%, supplied by EM Science Ethanol, supplied by Mallinckrodt, St. Louis, Mo.

HPLC Assays

An HPLC method was used to determine the rate of in vitro release of apomorphine HCl (“ApoH”) or loratidine (“LA”) from the implants. Chromatography was performed using a Zorbax SB-C 18 (250 mm×4.6 mm) column and 60% 0.1 trifluoro acetic acid in water, 15% methanol, 25% acetonitrile as the mobile phase, and ...

example 2

In Vitro Characterization of Extruded Implantable Devices

Extruded rods prepared as described above were characterized for total drug load and for rate of drug release.

Assessment of Drug Loading

Implants prepared with 70% ApoH:30% EVA were cut into 2 mm pieces, accurately weighed, and placed into 250 ml volumetric flasks. Approximately 200 ml of methanol was added to each flask and the solution was continuously stirred at room temperature until the implants was dissolved. The solution was then assayed for drug content.

The average ApoH content for unwashed, washed, and sterilized rods was between 66.9 and 67.9% ApoH, corresponding to 95.6 to 97% recovery.

Assessment of Drug Release

Experiments were performed to determine the rate of apomorphine released from the extruded rods. The medium for these studies was 0.5% sodium dodecyl sulfate (“SDS”). Preweighed rods were placed in 100 ml screw cap jars containing 50 ml of medium and placed on an orbital shaker. The orbital shaker ...

example 3

In Vivo Evaluation of Drug Loaded Implantable Devices

Four MPTP-lesioned, L-DOPA-naïve cynomolgus monkeys were administered three 2.4 mm diameter×2.6 cm length rod-shaped implantable devices prepared as described above, each containing 33% vinyl acetate and loaded with 98 mg+10% apomorphine HCl (68.5% apomorphine). Devices were implanted between the shoulder blades using a trocar. For comparison, three additional MPTP-lesioned, L-DOPA-naïve monkeys received pulsatile daily subcutaneous injections of apomorphine at a dosage of 0.2 mg / kg, which is the minimally-effective dose to achieve “ON” status in the animal.

All of the monkeys that received apomorphine implants were continuously in an “ON” state within one day after implantation, with an average steady state apomorphine level of approximately 0.5-1.0 ng / ml achieved after an initial burst. In contrast, animals that received pulsatile injections were “ON” for only approximately 90 minutes after each administration of apomorphine....

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
timeaaaaaaaaaa
lengthaaaaaaaaaa
diameteraaaaaaaaaa
Login to View More

Abstract

The present invention provides compositions, methods, and kits for treatment of Parkinson's disease and other conditions for which treatment with a dopamine agonist is therapeutically beneficial. The invention provides a biocompatible nonerodible polymeric device which releases dopamine agonist continuously with generally linear release kinetics for extended periods of time. Dopamine agonist is released through pores that open to the surface of the polymeric matrix in which it is encapsulated. The device may be administered subcutaneously to an individual in need of continuous treatment with dopamine agonist.

Description

TECHNICAL FIELD The invention provides a nonbioerodible, polymeric device for subcutaneous implantation and sustained release of dopamine agonist for treatment of Parkinson's disease and other conditions for which administration of a dopamine agonist is therapeutically beneficial. BACKGROUND OF THE INVENTION Parkinson's disease, a progressive neurodegenerative disorder, is characterized by loss of neurons that synthesize and release dopamine. This loss of dopaminergic neurons manifests itself in symptoms such as rigidity, resting tremors (shaking), poverty of movement (akinesia), slowness of movement (bradykinesis), and changes in gait and posture. Treatment of Parkinson's disease generally is based on therapeutic administration of substances that can compensate for the lack of dopaminergic neurotransmission due to the loss of dopamine-secreting neurons. A classic treatment regime includes chronic oral administration of levodopa, which is decarboxylated in the brain to form dopami...

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(United States)
IPC IPC(8): A61K9/00A61K9/14A61K9/16A61K31/381A61K31/4045A61K31/428A61K31/48A61K31/485A61L31/04A61L31/16A61P25/16
CPCA61K9/0024A61K9/146A61L2300/41A61K9/1635A61K31/381A61K31/4045A61K31/428A61K31/48A61K31/485A61L31/048A61L31/16A61L2300/20A61L2300/40C08L31/04A61K31/198A61P15/00A61P15/10A61P25/00A61P25/14A61P25/16A61P29/00A61P43/00A61K9/20A61L31/10A61L31/125A61L31/146A61L2300/602A61L2300/606A61L2300/62A61L2420/04
Inventor PATEL, RAJESH A.BUCALO, LOUIS R.COSTANTINI, LAURENKLEPPNER, SOFIE
Owner TITAN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com