Injectable depot gel composition and method of preparing the composition

Abstract

An injectable depot gel composition containing a polymer, a solvent that can dissolve the polymer and thereby form a viscous gel, a beneficial agent; and an emulsifying agent in the form of a dispersed droplet phase in the viscous gel. The injectable depot gel composition can be prepared by mixing the polymer and the solvent so that the solvent dissolves the polymer and forms a viscous gel. The beneficial agent is dissolved or dispersed in the viscous gel and the emulsifying agent is mixed with the beneficial agent containing viscous gel. The emulsifying agent forms a dispersed droplet phase in the viscous gel to provide the injectable depot gel composition. The injectable depot gel composition can deliver a beneficial agent to a human or animal with a desired release profile.

Description

[0001] This application claims the priority of provisional application Ser. No. 60 / 033,439, filed Dec. 20, 1996 and is a continuation of utility patent application Ser. No. 08 / 993,031, filed on Dec. 18, 1997.BACKGROUND OF THE INVENTION[0002] 1. Field of the Invention[0003] The present invention relates to a depot gel composition that can be injected into a desired location and which can provide sustained release of a beneficial agent. The present invention also relates to a method of preparing the composition.[0004] 2. Description of the Related Art[0005] Biodegradable polymers have been used for many years in medical applications. Illustrative devices composed of the biodegradable polymers include sutures, surgical clips, staples, implants, and drug delivery systems. The majority of these biodegradable polymers have been based upon glycolide, lactide, caprolactone, and copolymers thereof.[0006] The biodegradable polymers can be thermoplastic materials which means that they can be h...

AI Technical Summary

Benefits of technology

[0065] In accordance with various aspects of the present invention, one or more significant advantages can be obtained. More specifically, using simple processing steps, one can obtain a depot gel composition that can be injected into place in an animal without surgery using a low dispensing force through standard needles. Once in place, the composition will quickly return to its original viscosity and may exhibit rapid hardening so as to substantially avoid a burst effect and provide the desired beneficial agent release profile. Furthermore, once the beneficial agent has been fully administered, there is no need to remove the composition since it is fully biodegradable. As a still further advantage, the present invention avoids the use of microparticle or microcapsulation techniques which can degrade certain beneficial agents, like peptide and nucleic acid-based drugs and which microparticles and microcapsules maybe difficult to remove from the environment of use. Since the viscous gel is formed without the need for water, temperature extremes, or other solvents, suspended particles of beneficial agent remain dry and in their original configuration, which contributes to the stability of thereof. Further, since a mass is formed, the injectable depot gel composition may be retrieved from the environment of use if desired.

Problems solved by technology

Although thermoplastic and thermosetting biodegradable polymers have many useful biomedical applications, there are several important limitations to their use in the bodies of various animals including humans, animals, birds, fish, and reptiles.

While this characteristic is essential for some uses, it is a drawback where it is desired that the material flow to fill voids or cavities where it may be most needed.

These incisions are sometimes larger than desired by the medical profession and occasionally lead to a reluctance of the patients to accept such an implant or drug delivery system.

Although these materials can be injected into the body with a syringe, they do not always satisfy the demand for a biodegradable implant.

When inserted into certain body cavities such as a mouth, a periodontal pocket, the eye, or the vagina where there is considerable fluid flow, these small particles, microspheres, or microcapsules are poorly retained because of their small size and discontinuous nature.

Further, the particles tend to aggregate and thus their behavior is hard to predict.

In addition, microspheres or microcapsules prepared from these polymers and containing drugs for release into the body are sometimes difficult to produce on a large scale, and their storage and injection characteristics present problems.

Furthermore, one other major limitation of the microcapsule or small-particle system is their lack of reversibility without extensive surgical intervention.

That is, if there are complications after they have been injected, it is considerably more difficult to remove them from the body than with solid implants.

A still further limitation on microparticles or microcapsulation is the difficulty in encapsulating protein and DNA-based drugs without degradation caused by solvents and temperature extremes.

With solvent-based depot compositions comprised of a polymer dissolved in a solvent, one problem which exists is that the composition solidifies slowly after injection as solvent diffuses from the depot.

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