Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
2000-11-21
2003-07-01
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S422000, C424S423000, C424S426000
Reexamination Certificate
active
06586009
ABSTRACT:
Method for manufacturing a powder component for cement for medical use, use of such powder component and such powder component.
Aseptic loosening is the main long term complication after a total joint replacement. The osteolysis seen in loosening is caused by, in combination, an increased fluid pressure and an increased inflammatoric response to particles, preferably particles of high density polyethylene (HDPE). Another contributing main factor to loosening is related to the prosthetic stability within bone cement or between the cement and bone tissue.
Contrast agents such as barium sulphate (BaSO
4
) and zirconium dioxide (ZrO
2
) have been added to cement for medical use to achieve radiographic visibility, i.e. visibility to radiophotography, in order to check the operation result.
In order to improve the interface of cement for medical use, various substances such as e.g. hydroxyapatite and growth factors have been added to the cement. Hydroxyapatite has, inter alia, been used in compositions intended for reduction of the wear caused by fragmentation of the cement, whereby particles of the cement enter the joint cavity, i.e. the implant articulation.
There is today clear evidence that agents impermeable to X-ray emission, i.e., radio opaque agents, which are harder than the metallic counterpart, may cause damages to the articulating surfaces, whereby the wear of the polyethylene increases markedly. In the vast majority of total joint replacement, one of the articulating or bearing surfaces consists namely of a hard, very smooth metallic or ceramic surface, while the other bearing surface is manufactured from high-molecular weight polyethylene. This polyethylene is used as a concave bearing surface. It has been shown that if the radiographic or X-ray contrast media are removed from the bone cement, wear will be reduced. Thus, it is of utmost importance either to abandon said X-ray contrast media, which is disliked by most surgeons, or to find an X-ray contrast medium which will not affect the strength to a greater extent than in existing cements for medical use, but will be less abrasive when fragmented (released) from the cement.
This is possible by using new types of X-ray contrast media, so called non-ionic contrast media. Radiographic or X-ray contrast media of different types with high osmolality and low osmolality are known today. These contrast media have a high affinity for absorbing water and are in fact water soluble. Preliminary experiments regarding the possibility of mixing these X-ray contrast media into bone cement have been carried through in a laboratory and shows that this is possible and that good radiographic visibility, or visibility to radiophotography, is achieved. Studies are also carried through with bone cell cultures in order to study local toxicity. Existing studies show that non-ionic X-ray contrast media, without being added to bone cement, have very low toxicity especially when contrast media having low osmolality are used.
The sterilization procedure is of utmost importance for the production of a new cement for medical use. With the non-ionic, water soluble, radiography or X-ray contrast medium, gas sterilization will induce formation of lumps in the bone cement and sterilization by radiation will be necessary. There is, however, a clear influence by the sterilization upon a range of cement properties. The tensile strength decreases in proportion to the dosage of gamma and beta radiation for the sterilization. The fatigue resistance will also be significantly reduced. Rheology measurements show a large decrease in viscosity and a delay of the setting time after radiation. This effect on acrylic cement by oxidative degradation has been shown to occur also in other polymers, or plastic substances, such as HDPE. If radiation is carried through in air, this will cause extensive oxidation and property deterioration in HDPE. This effect increases with time due to ageing of the material. It has been shown that if radiation is carried through at a negative pressure and/or by means of a protective inert gas, the dominant effect of the radiation will be cross-linking, not degradation. The effect is further improved if the plastic product after sterilization by radiation is subjected to a heat treatment in an environment free of oxygen. Sterilization at a negative pressure and at low temperature also provide improved properties to the polymer.
The object of the present invention is consequently to provide a method for manufacturing the powder component for a cement for medical use in order to prevent the cement obtained from releasing particles which contribute to the wear of articulating or bearing surfaces adjacent the point of cementation as well as minimize the risk of damaging the powder component during sterilisation thereof.
This is arrived at according to the invention by the combination that a water soluble non-ionic X-ray contrast medium is mixed with the plastic substance, whereby particles of the X-ray contrast medium released from the cement after the cementation are dissolved and do not thereby contribute to the wear of articulating or bearing surfaces adjacent the point of cementation, and that sterilisation by radiation of the powder component containing said X-ray contrast medium is carried through at a negative pressure and/or in an inert gas atmosphere in order to minimize the risk of damaging the powder component during the sterilization thereof. The invention also include eventual heat treatment of the powder mixture in the oxygen-free atmosphere after the radiation treatment.
The object of the present invention Is also to render it possible to use the powder component manufactured by said method in a cement which is used as bone cement.
A further object of the invention is to provide a powder component which is manufactured in accordance with the abovementioned method.
Below, a method of manufacturing the powder component for a cement for medical use is described. The cement includes a liquid component containing a polymerisable substance and a powder component containing a plastic substance and an X-ray contrast medium. The liquid and powder components are adapted to be mixed and thereby provide a setting mass which is set to form the cement. A water soluble, non-ionic X-ray contrast medium is mixed with the plastic substance, whereby particles of the X-ray contrast medium released from the cement after cementation are dissolved and do not thereby contribute to the wear of articulating or bearing surfaces adjacent the point of cementation.
Sterilisation by radiation of the powder component containing said X-ray contrast medium is carried through at a negative pressure and/or in an inert gas atmosphere for minimizing the risk of damaging the powder component during the sterilisation.
The water soluble non-ionic X-ray contrast medium which is mixed into the powder component is chosen preferably from the group consisting of iohexol, ioversol, iopamidol, iotrolane, and iodixanol and has preferably low osmolality. Other X-ray contrast media which can be used are metrizamide, iodecimol, ioglucol, ioglucamide, ioglunide, iogulamide, iomeprol, iopentol, iopromide, iosarcol, iosimide, iotasul, ioxilane, iofratol and iodecol. Mixtures of the media can also be used.
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Bone Support AB
Fubara Blessing
Page Thurman K.
Tarolli, Sundheim Covell & Tummino L.L.P.
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