Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-01-17
1997-07-08
Kunz, Gary L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 62, H61K 31715
Patent
active
056461291
DESCRIPTION:
BRIEF SUMMARY
This application is the U.S. national stage entry under 35 U.S.C. 371 of PCT/EP93/00932, filed on Apr. 16, 1993.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the use of various fractions of hyaluronic acid as osteoinductive agents, i.e., agents capable of stimulating the growth and differentiation of bone forming cells, and therefore the formation of new bone material itself. The type of activity refers to cells of mammalian origin.
2. Description of Related Art
An intricate network of macromolecules constituting the extracellular matrix, a substantial part of the tissue volume, largely fills the extracellular space. In many tissues, such as connective tissues, it is generally more abundant and completely surrounds the cells on all sides, thus determining the physical properties of the tissue. The extracellular matrix is of considerable importance in regulating many processes of tissue behavior. It has been demonstrated that changes in the state and composition oft he extracellular matrix profoundly influence biosynthetic processes and tissue development.
Glycosaminoglycans (GAGs) are the most plentiful non-fibrous, extracellular macromolecules, and are ubiquitous in all connective tissues. This group of high molecular weight anionic glycoconjugates is present in both the soft and mineralized connective tissues. They are substantially composed of large molecules called "non-collagenous proteins" (NCP) of the extracellular matrix, or "proteoglycans". The first of these terms distinguishes these molecules from the group of fibrous proteins such as collagen, elastin, fibronectin and laminin; the second indicates that they are usually found to be covalently bound to protein.
The biological properties of proteoglycans have been the object of intense research, mainly with regard to the soft tissues. The bone and cement, on the other hand, have been virtually ignored as far as their proteoglycan content is concerned. In fact, there is only one report in existence which describes the proteoglycans of the alveolar bone (R. J. Waddington et al., Connective Tissue Res., 1988: 17, 171).
GAGs are long, unbranched polysaccharide chains composed of repetitive disaccharide units. The type of sugar residues, their bonds, and the number and position of the sulfate groups have led to the identification of four main groups of GAGs: 1) hyaluronic acid, 2) chondroitin solfate and dermatan sulfate, 3) heparan sulfate and heparin, and 4) keratan sulfate. It is important to note that GAGs (with the probable exception of hyaluronic acid) rarely exist in a free state within tissues. They are usually covalently bound to proteins.
With the exception of hyaluronic acid, GAGs contain sulfate groups, which together with carboxy groups, form a molecule with a highly negative charge under physiological conditions.
Hyaluronic acid (HA), also called hyaluronan or hyaluronate, contains up to several thousand sugar residues. It is a relatively simple molecule composed of regular sequences of non-sulfated disaccharide units.
HA is considered capable of facilitating cell migration during morphogenesis and tissue repair. It is found in varying quantities in all tissues and fluids in adult animals, and is particularly abundant in early embryos. Because of its simplicity, HA could represent the earliest evolutionary form of glycosaminoglycan. There is a correlation between HA production and mesenchymal cell movement on the one hand, and between HA distribution and cell differentiation on the other (B. Toole et al., Proc. Nat. Acad. Sci., USA, 1972: 69, 1384). The wound healing process possesses some aspects in common with early events which occur during the embryonic development of many organs, and HA plays an important role in both processes (B. P. Toole (1976) in S. H. Barondes, Ed., Neuronal Recognition, Plenum Press, New York, pp. 275-329); a correlation has been found between HA and cell adhesion, in terms of HA receptors (Goldstein et al., Cell, 1989: 56, 1063; I. Stamenkovic et al, Cell, 1989: 56,
REFERENCES:
patent: 5079236 (1992-01-01), Drizen et al.
patent: 5137875 (1992-08-01), Tsunenaga et al.
Callegaro Lanfranco
Romeo Aurelio
FIDIA S.p.A.
Fonda Kathleen Kahler
Kunz Gary L.
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