Controlled and directed local delivery of anti-inflammatory compositions

A composition, topical technology, applied in the field of pain reduction or elimination system, which can solve the problems of insufficient filling of patients' needs, prolonged drug action time, limited drug amount, etc.

Inactive Publication Date: 2007-10-17
WARSAW ORTHOPEDIC INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method is limited in the amount of drug that can reach the target site through the tissue
This approach does not adequately meet patient needs
Anti-TNF therapy often requires prolonged drug action, necessitating repeated injections

Method used

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  • Controlled and directed local delivery of anti-inflammatory compositions
  • Controlled and directed local delivery of anti-inflammatory compositions
  • Controlled and directed local delivery of anti-inflammatory compositions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Randomly assign four animals per group with CCI "neuropathic pain". CCI animals are subjected to a series of behavioral tests (ie mechanical tactile allodynia and thermal nociception tests) following administration of test compounds by systemic injection or local delivery via Alzet(R) osmotic pumps. The first dose was given prior to the test and subsequent doses were given at the half-life of each compound.

[0083] Behavioral tests: Von Frey test; hot plate test

[0084] Compounds of interest were delivered locally by osmotic pump, and up to 8 behavioral trials (4 per behavior), including the baseline trial, were performed. The study duration was 22 days or less. Following systemic or topical administration, behavioral assays are performed as described below to determine the optimal dosing regimen for any proposed compound of interest that may be effective in the methods of the invention.

[0085] The activity of compounds was evaluated using an in vivo chron...

Embodiment 2

[0094] Comparison and assessment of protein-based inhibitors of TNFα function in a rat model of chronic constriction injury (CCI): systemic versus local delivery

[0095] On the day of the start of surgery, a systemic dose of the compound is given by subcutaneous injection, and then the dosing period is determined by the half-life of the compound. The initial dose level of the compound should be administered by repeated injections. Local administration of the compounds is achieved by constant local infusion through implanted osmotic pumps.

[0096]Behavioral tests: Von Frey filament test (days 7, 14 and 21), thermal hyperalgesia test (days 8, 16 and 22).

[0097] therapy group

number of animals

systemic administration

Topical administration

Carrier (CCI only)

7

7

Gabapentin (positive control)

7

7

Compound 1

7

7

Compound 2

7

7

Compound 3

7

7

total

...

Embodiment 3

[0102] PLGA 50:50 / rhBMP-2 microsphere preparation

[0103] Dichloromethane (Aldrich MO 02249E0, D=1.325) was used as solvent. PLGA 50 / 50 was obtained from Sigma (Lactel BP-0100, Lot 56H1176). Recombinant human bone morphogenetic protein (rhBMP) (7.31 mg / vial) was prepared in the laboratory according to methods previously described and known to those skilled in the art. Dissolve 1 vial of rhBMP in 1 ml sterile water (preferably filter sterilized). PLGA (513.4 mg) was dissolved in 8 mL of dichloromethane.

[0104] The rhBMP was first dissolved in sterile water, and then the aqueous BMP solution was emulsified in the PLGA polymer solution. Briefly, combine 0.5 mL of BMP solution and 4 mL of PLGA / MeCl 2 , emulsify with a homogenizer (medium setting) for 45 seconds. Transfer the emulsion into a syringe with an 18-gauge needle. Add 60 ml of 3% PVA to a 150 ml glass beaker. The homogenizer was set at 3, the 3% PVA solution was stirred, and the emulsified polymer / BMP solution w...

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Abstract

The invention provides a method for alleviating pain associated with neuromuscular or skeletal injury or inflammation by controlled and directed delivery of one or more biological response modifiers to inhibit the inflammatory response which ultimately causes acute or chronic pain. Controlled and directed delivery can be provided by implantable or infusion pumps, implantable controlled release devices, or by sustained release compositions comprising biological response modifiers.

Description

field of invention [0001] The present invention relates to systems and methods for reducing or eliminating pain, particularly pain associated with musculoskeletal disorders, injuries or surgical procedures. More specifically, the invention relates to methods of administering biological response modifiers to inhibit or eliminate inflammatory responses that may lead to acute or chronic pain. Background of the invention [0002] Tumor necrosis factor alpha (TNF-α) emerges early in the inflammatory cascade following infection or injury. It is produced by monocytes, macrophages and T lymphocytes. TNF-α mainly acts on monocytes, synovial macrophages, fibroblasts, chondrocytes and endothelial cells, and stimulates the synthesis of pro-inflammatory cytokines and chemokines. It activates granulocytes and increases the expression of MHC class II (molecule). It promotes the secretion of matrix metalloproteinases (MMPs), leading to the degradation of cartilage matrix. Because it can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K31/00A61K39/00A61M31/00A61K38/17
CPCA61K9/0024A61K38/1793A61K38/1709A61K38/1875A61K2300/00
Inventor W·F·麦克凯J·M·扎内拉
Owner WARSAW ORTHOPEDIC INC
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