Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1998-07-28
2001-07-17
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S426000
Reexamination Certificate
active
06261583
ABSTRACT:
BACKGROUND OF THE INVENTION
A variety of approaches have been developed for administering a biologically active agent to a patient in a continuous or sustained manner. However, currently available approaches often involve disadvantages or limitations.
In many conventional controlled release systems, the active agents are incorporated into solid, monolithic polymeric matrices. The matrices are hard, unpliable and when surgically implanted into patients' bodies, cannot be molded to conform to the shape of the implant pocket. Often, the sizes and shapes of the matrices and the surgical implantation lead to patient discomfort and complications. In recent years, injectable systems such as polymer solutions and dispersions of microparticles have been developed to overcome these problems. The injectable systems incorporating polymer solutions, however, depend upon the transformation phenomenon associated with the insoluble polymer and aqueous based body fluid. If there is a low quantity of available aqueous fluid at the implant site or the injectable system does not permit substantial influx of water, it does not transform within a reasonable time.
Therefore, development of a surgically implantable solid implant that is moldable and shapable for easy placement and adaptation to the implant site, but then becomes hard and rigid after implantation in the body.
SUMMARY OF THE INVENTION
The invention is directed to an implant composition that exhibits such physical properties as moldability, pliability and extrudability. The invention is also directed to a method of use of the implant composition.
The implant composition is composed of a biocompatible, biodegradable, water-insoluble thermoplastic polymer in combination with a bioactive agent, a biocompatible organic solvent and a small amount of an aqueous medium. The aqueous medium causes the thermoplastic polymers in the implant composition to coagulate at least in part so that the physical form of the implant composition is a pliable, moldable solid.
In use, the implant composition continues its transition to a solidified mass. When implanted at a site infused with body fluid, the composition rapidly continues through this transition to become a fully solidified implant. When little or no body fluid is present at the implant site, the transition to a fully solidified mass occurs at a slower rate. Nevertheless, the integrity of the implant remains because the composition has a pliable, moldable solid nature.
The pliability of the composition can be substantially maintained throughout its life as an implant if a certain subgroup of the organic solvent of the composition is used. Such organic solvent also can act as a plasticizer for the thermoplastic polymer and at least in part may remain in the composition rather than dispersing into body fluid, especially when the organic solvent has low water solubility. According to the invention, this subgroup is termed an organic liquid. An organic liquid having these low water solubility and plasticizing properties may be included in the composition in addition to an organic solvent that is highly water soluble. In the latter situation, the first organic solvent preferably will rapidly disperse into the body fluid.
Because the implant composition of the invention is moldable and pliable, a method of use for the implant composition involves its insertion into a patient by a simple surgical procedure. The moldable, pliable character enables the surgeon to conform the implant composition to the shape of the surgically constructed pocket. Its pliable character also increases the comfort of the patient when it is implanted.
BRIEF DESCRIPTION OF THE DRAWINGS
DETAILED DESCRIPTION OF THE INVENTION
The invention provides a composition and method for controlled release delivery of a biologically active agent. The invention enables effective development of sustained blood and/or tissue levels of agent. The composition includes a thermoplastic polymer which is dispersed or dissolved in an organic solvent, a biologically active agent, an optional organic liquid and a small amount of aqueous medium such as water.
Definitions
The term “moldable” in the context of the present invention means being capable of deforming into, shaping to, or adapting to any three dimensional shape.
The term “pliable” in the context of the present invention means being capable of deforming, bending or flexing under minimal or slight pressure.
The term “flowable” in the context of the present invention means having a viscosity that will permit displacement of a material having this characteristic without application of pressure. A flowable composition is manipulatable, will pass through a small to moderate sized orifice without application of pressure and may be shaped and molded within the tissue defect. Flowable compositions in this context include those having a consistency from that of an emulsion or suspension with a low viscosity or water-like consistency, to that of a high viscosity such as cold molasses.
The term “biocompatible” in the context of the present invention means not causing substantial tissue irritation or necrosis at the implant site.
The term “biodegradable” means degrading over time by the action of enzymes, hydrolytic action and/or other similar mechanisms and “biodegradable” includes the terms bioerodable and bioabsorbable.
The term “bioerodible” means that the implant erodes or degrades at its surfaces over time due, at least in part, to contact with substances found in the surrounding tissue fluids, or by cellular action.
The term “bioabsorbable” means that the resulting implant is broken down and absorbed within the patient's body, for example, by a cell or tissue.
The term “implant site” means a site, in or on which the controlled release formulation is formed or applied, for example, a soft tissue such as muscle or fat, or a hard tissue such as bone. Examples of other implant sites include, but are not limited to, a tissue defect such as a tissue regeneration site; a void space such as a periodontal pocket, a surgical incision or other formed pocket or cavity; a natural cavity such as the oral, vaginal, rectal or nasal cavities, and the cul-de-sac of the eye.
The term “extrudable” in the context of the present invention means that under pressure, a material can be forced as a putty through an orifice.
Implant Composition
The implant composition of the invention includes a biologically active agent in mixture with a moldable, pliable solid formed from a biodegradable, biocompatible, water-insoluble thermoplastic polymer, an organic solvent, an optional organic liquid and a small amount of an aqueous medium.
The implant composition can be prepared by any combination of steps in which the aqueous medium is added to a mixture of the organic solvent and thermoplastic polymer, hereinafter termed “flowable composition”, and the biologically active agent is present either in the flowable composition or the aqueous medium. For example, the thermoplastic polymer and organic solvent can first be combined to form the flowable composition as an intermediate. The biologically active agent can be included simultaneously with or subsequent to formation of the flowable composition. The small amount of aqueous medium can then be added slowly to the flowable composition, with stirring or otherwise mixing to form the pliable, moldable implant composition of the invention. A second method involves dissolving the biologically active agent in the aqueous medium and adding it to the flowable composition to solidify the mixture and entrap the active agent.
Biologically Active Agent
According to the invention, a biologically active agent forms part of the implant composition. The biologically active agent is an agent that is capable of providing a local or systemic biological, physiological or therapeutic effect in the body of a patient. The biologically active agent is combined with the other ingredients of the implant composition to form the pliable, moldable solid implant composition. The implant composition posses
Chandrashekar Bhagya L.
Dunn Richard L.
McEnery Kathleen A.
Atrix Laboratories, Inc.
Joynes R.
Page Thurman K.
Schwegman Lundberg Woessner & Kluth P.A.
LandOfFree
Moldable solid delivery system does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Moldable solid delivery system, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Moldable solid delivery system will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2517897