Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2001-04-18
2002-10-08
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S423000, C424S422000, C514S772300
Reexamination Certificate
active
06461632
ABSTRACT:
FIELD OF INVENTION
This invention is directed to a method for delivering a drug via a hardenable ceramic hydraulic cement composition, implanted in an animal or human, that both hardens and dissolves or degrades in situ after time to release a therapeutically effective amount of the drug into a locally targeted area. The invention further relates to the cement composition obtainable according to the method described, including a first component of at least one sodium or calcium salt of inorganic and organic acids, a second component of at least one alkaline, and optionally third and fourth components including an organic carboxylic acid and pure water, respectively.
BACKGROUND OF THE INVENTION
Ceramic cements which harden in situ can be used for various applications. Such cements may be applied to reinforce porotic bones, to enhance fixation of fractures of porotic bones, to fill bone defects or to release bone growth factors.
Recently, resorbable cements, consisting of &bgr;-tricalciumphosphate, monocalcium phosphate and so-called carbonized cements containing calcium carbonate, became known that set at body temperature. These known cements have the disadvantage of long resorption or dissolution times. While this property is indispensable when cements are used to enhance bone fracture fixation, it is undesirable when cements are applied as carriers for fast local delivery of drugs.
The invention as claimed aims at solving both of the above described problems.
SUMMARY OF THE INVENTION
The invention relates to a ceramic hydraulic cement composition that includes a first component including at least one of a calcium or sodium salt of an inorganic and/or organic acid and a second component including an alkaline component. The invention also related to a method of delivering the composition which includes providing a first component including at least one of a calcium or sodium salt of an inorganic and/or organic acid; providing a second component including an alkaline component; mixing the first and second components to form a ceramic hydraulic cement composition; and implanting a therapeutically effective amount of the composition into an animal or human, preferably human. The composition hardens in situ and degrades in situ after a period of time to release a drug to a locally targeted area, preferably a bone defect. The composition preferably degrades within 10 hours to 4 months, preferably within 10 hours to 30 days.
The calcium or sodium salt can include carbonic acid, phosphoric acid, or glycerophosphoric acid, or mixtures thereof. Preferably, wherein the salt includes at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate. The first component can further include a therapeutically active agent.
The second component preferably includes sodium silicate or calcium silicate and is preferably present in the composition in an amount from 0.01 to 10 weight percent. In one embodiment, the second component also includes water.
In another embodiment, the composition further includes a third component, preferably an organic carboxyclic acid, and more preferably at least one of ascorbic acid, citric acid, or tartaric acid.
In one embodiment, the composition includes an osteogenic agent., preferably at least one of growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention provides a method for delivering a composition by implanting a hardenable ceramic hydraulic cement into a body, as defined in the claims. The main advantage of the invention is the relatively short dissolving time of the hardened implanted cement compared to the above mentioned prior art cements which allows for faster delivery of drugs, in particular of osteogenic drugs.
In a preferred embodiment of the invention, a further component C, which is an organic carboxylic acid, is used. The organic carboxylic acid may be chosen from the group of ascorbic acid, citric acid or tartaric acid and has the function of neutralizing the alkaline components (sodium or calcium silicate) of the cement. Further advantages are the better compatibility with the environment and the faculty to complex calcium ions from the body fluids more easily and to deposit in the bone defect treated with the cement. The use of ascorbic acid, in particular, further contributes to the formation of collagen in the bone defect treated with the cement.
Component A may preferably comprise calcium and/or sodium salts of carbonic acid, phosphoric acid or glycerophosphoric acid which are highly biocompatible, in particular if selected from the group of hydroxyapatite (HA), tricalcium phosphate (TCP), calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate or calcium glycerophosphate.
In a preferred embodiment water is incorporated in component B prior to mixing in order to obtain a shorter mixing time.
In a more preferred embodiment, the concentration of the aqueous solution of sodium or calcium silicate of component B is in the range of 0.01% to 10.00% which facilitates preparation of the cement and thus contributes in controlling the acidity thereof.
In a further preferred embodiment, the drugs added to the cement are chosen from the group of: osteogenic drugs, tissue growth factors (TGF-beta), osteocalcines, calcium binding proteins (GLA), bone morphogenetic proteins (BMP), antimicrobial drugs or vitamins. The concentration is specific for the particular application and drug used.
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Bennett Rachel M.
Page Thurman K.
Pennie & Edmonds LLP
Synthes (U.S.A.)
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