Promoter for regeneration of tendon-bone junction tissue or ligament-bone junction tissue
Inventors
Tomita, Katsuro • Tsuchiya, Hiroyuki • Kitaoka, Katsuhiko • Nakase, Junsuke • Hanada, Keigo • Matsumoto, Kunio
Assignees
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Publication Number
US-8927493-B2
Publication Date
2015-01-06
Expiration Date
Abstract
An object of the present invention is to provide a drug for promoting the regeneration of tendon-bone junction tissue or ligament-bone junction tissue. The present invention relates to a promoter for regeneration of tendon-bone junction tissue or ligament-bone junction tissue including the following (1) or (2) as an active ingredient: (1) the following (1-a), (1-b), or (1-c) (1-a) HGF protein,(1-b) a partial peptide of HGF protein, the peptide having an effect of promoting regeneration of tendon-bone junction tissue or ligament-bone junction tissue,(1-c) a salt of (1-a) or (1-b); (2) DNA including the following (2-a), (2-b), or (2-c), (2-a) DNA encoding HGF protein,(2-b) DNA encoding a partial peptide of HGF protein, the peptide having an effect of promoting regeneration of tendon-bone junction tissue or ligament-bone junction tissue,(2-c) DNA encoding a protein or a peptide, the protein or the peptide having an effect of promoting regeneration of tendon-bone junction tissue or ligament-bone junction tissue, and the DNA hybridizing with DNA comprising a base sequence complementary to (2-a) or (2-b) under a stringent condition.
Core Innovation
The invention relates to administering a Hepatocyte Growth Factor (HGF) protein having an amino acid sequence at least 95% homologous to the amino acid sequence represented by SEQ ID NO: 3, and having an effect of promoting regeneration of tendon-bone junction tissue or ligament-bone junction tissue. The invention further relates to using HGF protein in conjunction with locally applied formulations for such regeneration. The local application is directed to an interface region where the bone is in contact with the tendon or ligament, or to a space between the bone and the tendon or ligament.
The invention also includes providing a formulation consisting of the HGF protein and at least one member selected from aqueous solvent, tonicity agent, buffer solution, preservative, thickener, stabilizer, pH adjuster, solubilizing agent, oily solvent, propellant, and biodegradable polymer. In addition to HGF protein, the disclosed content includes HGF partial peptides and DNA encoding HGF, including sequence-homologous/strengent-hybridizing DNA. The described compositions are presented for topical application and for delivery using viral or nonviral vectors.
The disclosed experimental support describes an HGF-based promoter applied to post-surgical contact sites to promote earlier interface histological regeneration. The regeneration includes Sharpey-like fiber formation and orientation and maturation at tendon-bone or ligament-bone junction tissue interfaces. The disclosure further states that the approach improves tendon-bone junction rupture strength compared with saline controls, and includes representative sustained-release or microcapsule formulation approaches using biodegradable polymers.
Claims Coverage
The partial content includes one independent claim covering a local administration method for promoting regeneration of tendon-bone junction tissue and ligament-bone junction tissue. The main inventive features center on local interface application of an HGF protein (or a formulation containing it) and the selection of permissible HGF protein sequence homology relative to SEQ ID-defined sequences.
Local interface administration of an HGF protein to promote junction regeneration
A method for promoting regeneration of tendon-bone junction tissue or ligament-bone junction tissue consisting essentially of administering, to a patient with tendon-bone junction tissue injury or ligament-bone junction tissue injury, an HGF protein having an amino acid sequence at least 95% homologous to the amino acid sequence represented by SEQ ID NO: 3 and having an effect of promoting regeneration, wherein the HGF protein is locally applied to an interface region where the bone is in contact with the tendon or ligament, or a space between the bone and the tendon or ligament.
Formulation containing the HGF protein with biodegradable polymer and excipients for local delivery
A method for promoting regeneration of tendon-bone junction tissue or ligament-bone junction tissue consisting essentially of administering, to a patient with tendon-bone junction tissue injury or ligament-bone junction tissue injury, a formulation consisting of the HGF protein and at least one member selected from aqueous solvent, tonicity agent, buffer solution, preservative, thickener, stabilizer, pH adjuster, solubilizing agent, oily solvent, propellant, and biodegradable polymer, wherein the formulation is locally applied to an interface region where the bone is in contact with the tendon or ligament, or a space between the bone and the tendon or ligament.
Across the independent claim, the core coverage is the local administration of an HGF protein (or a formulation containing it) at the bone–tendon or bone–ligament interface or the space between them, using HGF sequence homology to SEQ ID NO: 3 and optionally a formulation including biodegradable polymer and selected formulation components.
Stated Advantages
Promotes regeneration of tendon-bone junction tissue or ligament-bone junction tissue.
Improves tendon-bone junction rupture strength compared with saline controls.
Supports earlier interface histological regeneration, including Sharpey-like fiber formation/orientation and maturation.
Documented Applications
Promoting regeneration at post-surgical contact sites involving a bone tunnel interface where a tendon graft or ligament graft is adhered to bone.
Ligament reconstruction surgery contexts including anterior cruciate ligament (ACL) reconstructive surgery, posterior cruciate ligament (PCL) reconstructive surgery, and collateral ligament reconstructive surgery.
MPFL reconstruction for recurrent patellar dislocation.
Lateral ankle ligament reconstruction.
Rotator cuff repair surgery for a shoulder joint.
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