Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Matrices
Reexamination Certificate
2000-09-08
2003-02-18
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Matrices
C424S486000, C424S489000, C424S490000, C424S497000
Reexamination Certificate
active
06521258
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to the use of supercritical fluid processing techniques to prepare polymer matrices suitable for use in orthopedic, pharmaceutical, and similar applications.
2. Reference to Related Patent Applications
Reference is hereby made to two concurrently filed patent applications filed by the inventors hereof, said applications being titled “Orthopedic Mixtures Prepared by Supercritical Fluid Processing Techniques,” application Ser. No. 09/658,252, and “Controlled-Release Pharmaceuticals Prepared by Supercritical Fluid Processing,” application Ser. No. 09/658,249, the disclosures of which are incorporated herein by reference. These applications will be referred to herein as the “Orthopedic Mixtures Patent” and the “Pharmaceutical Mixture Patent.”
3. Description of the Prior Art
There is a continuing need for high-strength orthopedic mixtures that can be used as bone filler, bone grafts, and the like. Similarly, there is a need for high quality pharmaceuticals, particularly pharmaceuticals whose active ingredient can be released slowly over an extended period of time. The Orthopedic Mixtures Patent and the Pharmaceutical Mixture Patent disclose and claim improvements in the manufacture of orthopedic mixtures and pharmaceutical mixtures that are brought about by the use of supercritical fluid processing techniques. Generally speaking, each of these inventions involves the discovery that an improved product can be made by (1) mixing desired ingredients in a reactor with a process medium that is, or can be made to become, a supercritical fluid, (2) mixing the ingredients in the reactor under supercritical fluid conditions to form a supercritical fluid slurry, and (3) releasing the pressure in the reactor in a controlled manner or discharging the reactor contents into a receiving vessel in a controlled manner. The resultant product is finely divided, porous particles that can be used in orthopedic or pharmaceutical applications.
In the case of the Orthopedic Mixtures Patent, a source of calcium ions such as tribasic calcium phosphate or hydroxyapatite is mixed with a polymer such as poly-&egr;-caprolactone (PCL) and a supercritical fluid such as carbon dioxide to form a porous, strong material that can be carved, molded, or poured into a suitable shape. The polymer forms a matrix that provides support and structure for the calcium ions. The polymer is biosorbable, so that a porous calcium structure that simulates autogenic bone will be left in the body.
In the case of the Pharmaceutical Mixture Patent, a biologically active ingredient such as an antibiotic is mixed with a polymer such as PCL or polylactide-co-glycolide (PLGA) and a supercritical fluid such as carbon dioxide to form porous polymer particles that are infused with the biologically active ingredient. In a manner analogous to the Orthopedic Mixtures Patent, the polymer forms porous particles that provide a matrix, or carrier, for the biologically active ingredient. The characteristics of the polymer are such that the active ingredient will be released slowly into the patient over time through delayed dissolution or controlled diffusion. In each of these inventions, the process conditions, particularly the temperature of the ingredients, the mixing time, and the manner in which (1) the supercritical fluid is released from the reactor or (2) the slurry is discharged from the reactor can be varied to control the size of the particles and the porosity thereof. Variations in the sizes of the particles and their porosity control the performance characteristics of the resultant products.
Despite the advances of the Orthopedic Mixtures Patent and the Pharmaceutical Mixture Patent, there remains a need for a polymer matrix suitable for orthopedic uses, pharmaceutical uses, and similar uses that has superior strength characteristics. The need for a high strength polymer matrix for orthopedic applications is apparent. Although the need for a high strength polymer matrix is less obvious in the pharmaceutical field, such a product is very important. This is because degradation of the polymer can have an undesirable effect on the release rate of the active ingredient carried by the polymer. Further, strength characteristics of the polymer are important when the pharmaceutical product is provided in such form as a tablet.
Desirably, a polymer matrix would be known that could be used to produce high strength orthopedic and pharmaceutical mixtures. Any such polymer matrix preferably would meet or exceed the performance characteristics of existing polymer matrices as described in the Orthopedic Mixtures Patent and the Pharmaceutical Mixture Patent. Any such polymer matrix desirably would be very easy to manufacture.
SUMMARY OF THE INVENTION
In response to the foregoing concerns, the present invention provides a new and improved polymer matrix and a process for its manufacture that can be used to make high strength orthopedic and pharmaceutical mixtures. Essentially, the invention involves the discovery that a polymer matrix having strength gains of several.orders of magnitude can be produced by blending, or alloying, known polymers. The resultant polymer matrices are homogeneous, have enhanced strength, and are not fractionated or degraded.
Polymer matrices according to the invention are prepared by charging a reactor with starting materials that include two or more polymers. A process medium is added to the reactor. The process medium preferably is carbon dioxide which is supplied to the reactor in a supercritical state or which is heated and pressurized in the reactor to attain a supercritical state. The heated and pressurized ingredients are mixed in the reactor for a period of time sufficient to form them into a homogeneous, gas-saturated suspension, or supercritical fluid slurry. After the ingredients have been mixed adequately, the slurry either is left in the reactor or is discharged into a receiving vessel where the process medium is separated from the remainder of the materials and removed, leaving finely divided particles behind.
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Mandel Frederick S.
Wang J. Don
Ferro Corporation
Page Thurman K.
Rankin, Hill Porter & Clark LLP
Tran S.
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