Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis – Bone
Reexamination Certificate
1999-06-18
2003-03-18
Prebilic, Paul (Department: 3738)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
Bone
C623S023580, C623S023610, C523S116000, C424S042000
Reexamination Certificate
active
06533820
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to new biomaterials, i.e., bonding solutions for granular bone replacements and bone replacements in the form of pastes, comprising hyaluronic acid and hyaluronic acid derivatives.
2. Description of Related Art
Hyaluronic acid
Hyaluronic acid is a natural polysaccharide composed of alternating residues of D-glucuronic acid and N-acetyl-D-glucuronic acid. It is a linear polymer with a wide molecular weight range, depending on the source from which it is obtained, how it is prepared, and how the molecular weight is determined. In nature, it is present in the pericellular gel, in the fundamental substance of the connective tissues of vertebrates, of which it is the main component, in the synovial fluid of joints, in the vitreous humor, in umbilical cord tissues, and in the combs of domestic fowl.
Specific hyaluronic acid fractions with definite molecular weights are known which do not possess inflammatory activity, and which can therefore be used to enhance wound healing or substitute for endobulbar fluids, or which can be used in therapy for joint pathologies by intraarticular injection, as described in European Patent No. 0138572, granted to Applicants.
Also known are hyaluronic acid esters wherein all or part of the carboxy groups of the acid are esterified, and their use in the fields of pharmaceuticals, cosmetics, and biodegradable plastic materials, as described in U.S. Pat. Nos. 4,851,521 and 4,965,353 also granted to Applicants.
It is known that hyaluronic acid plays a fundamental role in tissue repair processes especially in the first stages of granulation tissue formation, stabilizing the coagulation matrix and controlling degradation, favoring the recruitment of inflammatory cells such as polymorphonucleocytes and monocytes, of mesenchymal cells such as fibroblasts and endothelial cells, and directing the subsequent migration of epithelial cells.
It is known that the application of hyaluronic acid solutions to bedsores, wounds and burns accelerates healing. The role of hyaluronic acid in the various stages of tissue repair has been described, by constructing a theoretical model, by Weigel P. H. et al.: “A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing,”
J. Theor. Biol.,
119: 219, 1986.
Granular Bone Replacements
Granular bone replacements have been widely studied and used in dentistry and medicine owing to their biocompatible and osteoconductive properties, and because they easily fill cavities of various forms, such as those caused by alveolar bone shrinkage, postextraction cavities, and cystic cavities. The main difficulty when using this material is caused by its lack of binding properties, so that it easily becomes dislodged either during or after application. To overcome this drawback, various types of bonding materials have been proposed with which to prepare pastes containing bone granules. Fibrin is already being used, as described in patent applications JP A 60254640 and JP A 60254641.
One disadvantage of using fibrin as a bonding agent is that it can cause infection by the hepatitis virus, as well as by H.I.V. and other viruses, due to its human origin. Alternative materials have therefore been proposed, such as pullulan, chitin, glycol, carbomethylene chitin, and pectin, as described in patent application EP 0416398.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a viscous solution composed of hyaluronic acid and/or hyaluronic acid esters or salts of hyaluronic acid in association with antibiotics, used singly or in combination, to bind bone replacements in granular form for use in dentistry or surgery of all kinds. Such solutions have excellent biocompatible and bioabsorbable characteristics, and are not liable to cause problems such as infection.
Another object of the present invention is to provide a paste comprising a viscous solution of hyaluronic acid and/or hyaluronic acid esters or salts of hyaluronic acid in association with antibiotics, used singly or in combination, and bone granules. The granules incorporated in the paste are firmly adhered together, thus facilitating their use in dentistry and bone surgery.
Further scope of the applicability of the present invention will become apparent from the detailed description provided below. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
DETAILED DESCRIPTION OF THE INVENTION
The following detailed description is provided to aid those skilled in the art in practicing the present inventions Even so, the following detailed description should not be construed to unduly limit the present invention, as modifications and variations in the embodiments herein discussed may be made by those of ordinary skill in the art without departing from the spirit or scope of the present inventive discovery.
The contents of each of the references cited herein are incorporated by reference in their entirety.
The foregoing objects are achieved by dissolving hyaluronic acid, esters of hyaluronic acid, or salts of hyaluronic acid in association with antibiotics, used singly or in combination, in water, to form highly viscous solutions. The viscosity of such solutions is at least 15 Pa.s, preferably over 22 Pa.s, at a temperature of 25° C. and 50%±5% relative humidity. The nearer the viscosity to the lower limit, the more liquid the solution; the greater the viscosity, the denser the solution. The correct degree of viscosity for ideal working conditions is a subjective parameter which depends on the individual, who can alter its viscosity by varying the concentration of the solution. The properties of the material comprising the solution, such as its molecular weight, will be selected according to the required degree of viscosity.
The solution according to the present invention is prepared by solubilizing hyaluronic acid, the partial ester of hyaluronic acid or a mixture of the same, or a salt of hyaluronic acid in association with an antibiotic or a mixture of the same, previously sterilized with gamma rays, in sterile water or buffer.
The esters of hyaluronic acid that can be used in the present invention are described in U.S. Pat. Nos. 4,851,521 and 4,965,353, and in PCT publication WO 92-13579. the salts of hyaluronic acid in association with antibiotics that can be used in the present invention are descried in U.S. Pat. No. 5,166,331. these can be used singly or in various combinations with one another, or with hyaluronic acid.
The powder is placed in the solubilization vessel under a sterile hood at a temperature of 25° C.±2° C. and 50%±5% humidity. Solubilization can be achieved in a mixer composed of two spiral elements turning in opposite directions.
Operative conditions depend on the desired viscosity and can be as follows:
FINAL
SOLUBILIZATION
NO. TURNS
SOLUBILIZATION
VISCOSITY
TEMPERATURE
IN MIXER
DURATION
15 Pa · s
30° C. ± 5° C.
60 rpm
4 Hours
22 Pa · s
45° C. ± 5° C.
40 rpm
8 Hours
All air is eliminated from the solution before use by placing it in a vacuum for two hours (minimum 0.01 mbar). It is possible to sterilize a solution prepared with non-sterile material by filtering it through a filter with a pore size of 0.22 &mgr;m. In this case, to facilitate filtration, the solution can first be prepared at a lower viscosity than will be required for its application. It is then filtered and subsequently distilled under vacuum until it reaches the concentration corresponding to the desired viscosity. Solutions thus prepared can be mixed with bone granules to form a paste to be used to fill bone cavities and defects. The ratio between the quantity of solution and the quantity of granules is 1:3, w/w, or more
Callegaro Lanfranco
Dorigatti Franco
Romeo Aurelio
Fidia S.p.A.
Prebilic Paul
LandOfFree
Biomaterials for bone replacements does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Biomaterials for bone replacements, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Biomaterials for bone replacements will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3086269