Silver-containing, sol/gel derived bioglass compositions

Details Silver-containing, sol/gel derived bioglass compositions Silver-containing, sol/gel derived bioglass compositions

2000-06-14

2002-11-19

Pryor, Alton (Department: 1616)

Drug, bio-affecting and body treating compositions

Inorganic active ingredient containing

Heavy metal or compound thereof

Reexamination Certificate

active

06482444

ABSTRACT:

FIELD OF THE INVENTION
BACKGROUND OF THE INVENTION
Materials used for implantation in the human body to replace damaged or diseased tissue must be biocompatible and mechanically suitable for their intended use. Metallic and polymeric materials for biomedical applications present many problems due to their high Young's modulus (compared with that of bone), the formation of a non-adherent fibrous capsule (the resulting movement of which can lead to deterioration in function of the implant), or sometimes to their degradation products.
There is an increasing clinical use of bioactive glass and glass-ceramics because they offer the possibility of improving the long-term survivability of prostheses and improved repair of aged, diseased or damaged bone. These materials tend to form mechanically strong bonds to bone by means of a series of chemical reactions at the bone-implant interface. One of the major advantages of using a bioactive glass is the ability to control the surface chemistry, and in doing so, exerting control over the rate of bonding to the tissue.
Many biocompatible and bioactive biomaterials have been implanted. Associated problems of infections due to the intrinsic nature of an illness and to surgical intervention can arise as a consequence of implantation, even with currently aseptic surgical procedures.
Bioglass® is one example of a biocompatible material used to prepare implants. Bioglass® is often used to repair damage caused in bones, teeth, and skin where the potential for bacterial or mycotic infections is always present. An important example is osteomyelitis, one of the most dangerous diseases which is caused, in the majority of cases, by
S. aureus
, Salmonella or
K. kingea
(in children).
Even in cases of non-infectious diseases, post-operative conditions often require antibiotic treatment, which is usually administered orally. Unfortunately, this can cause bacteriological resistance to the drug, and often depletes the benign microbial flora normally present in the body, leading to gastrointestinal side effects.
Recent efforts have been focused on developing modified implant materials with antibacterial properties. Such implant materials must have suitable mechanical and chemical properties for their intended use. It would be advantageous to provide additional implant materials with antibacterial properties. The present invention provides such materials.
SUMMARY OF THE INVENTION
Silver-containing sol-gel derived bioactive glass compositions and methods of preparation and use thereof are disclosed. The compositions can be in the form of fibers, which can have any diameter between 1 &mgr; and 150 &mgr;m and can be either continuous or discontinuous or particles which can have any diameter for example, from 0.5 &mgr;m to 3 mm, or coatings which can have thicknesses, for example, from 0.05 to 100 &mgr;m. The bioactive glass (bioglass) used in the compositions includes various salts in the following ranges (weight percent of the bioglass composition):
SiO
2
40-90%
CaO
 6-50%
P
2
O
5
 0-12%
Ag
2
O
0.1-12% 
The fibers can be woven into mats and used to make structures useful, for example as bone graft substitutes and coverings for bony defects. The fibers can also be used to make three dimensional structures for preforms to be impregnated with polymers, for example biodegradable polymers. Such structures can be linked, covalently or ionically, to bioactive compounds, for example growth factors, antibiotics, antivirals, nutrients and the like, to enhance tissue repair and promote healing.
The compositions, preferably in the form of fibers or particles, can be incorporated into implanted materials such as prosthetic implants, sutures, stents, screws, plates, tubes, and the like. The compositions in the form of particles can be applied as bioactive layers on prosthetic implants. The compositions in the form of bioactive sol-gel coatings can be applied on the surface or in the pores of prosthetic implants of various configurations.
The compositions are also useful for tissue engineering applications. An advantage of using these compositions is that anti-bacterial properties can also be imparted to devices used for in vitro and ex vivo cell culture when the compositions are incorporated into tissue engineering devices.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Silver-containing sol-gel derived bioactive glass compositions and methods of preparation and use thereof are disclosed. The compositions can be in the form of fibers, which can have any diameter between 1 &mgr; and 150 &mgr;m and can be either continuous or discontinuous, particles which can have any diameter, for example from 0.5 &mgr;m to 3 mm, or coatings which can have thicknesses, for example from 0.05 to 100 &mgr;m. The compositions are prepared using a sol-gel method and can be used for a variety of medical uses, for example bone repair, biodegradable sutures, and tissue engineering applications.
I. Composition
As used herein the terms “bioactive glass” or “biologically active glass” mean an inorganic glass material having an oxide of silicon as its major component and which is capable of bonding with growing tissue when reacted with physiological fluids.
Bioactive glasses are well known to those skilled in the art, and are disclosed, for example, in
An Introduction to Bioceramics
, L. Hench and J. Wilson, eds. World Scientific, New Jersey (1993), the contents of which are hereby incorporated by reference.
The glass preferably includes between 40 and 90% by weight of silicon dioxide (SiO
2
), between about 6 and 50% by weight calcium oxide (CaO), between about 0 and 12% by weight phosphorus oxide (P
2
O
5
) and between about 0.1 and 12% by weight silver oxide (Ag
2
O). More preferably, the glass includes between 45 and 86% by weight of silicon dioxide oxide (SiO
2
), between about 10 and 36% by weight calcium oxide (CaO), between about 3 and 12% by weight phosphorus oxide (P
2
O
5
) and between about 3 and 12% by weight silver oxide (Ag
2
O).
CaF
2
, B
2
O
3
, Al
2
O
3
, MgO and K
2
O, Na
2
O may be included in the composition in addition to silicon, sodium, phosphorus and calcium oxides. Other silver salts than silver oxide can optionally be used. The preferred range for B
2
O
3
is between 0 and 10% by weight. The preferred range for K
2
O is between 0 and 8% by weight. The preferred range for Na
2
O is between 0 and 20% by weight. The preferred range for MgO is between 0 and 5% by weight. The preferred range for Al
2
O
3
is between 0 and 3% by weight.
It is preferred to use reagent grade glass, especially since the glass is used to prepare materials which ultimately may be administered to a patient.
In a preferred embodiment, the silver-containing, sol-gel derived bioactive glass is formed from various salts in the following ranges (weight percent of the bioglass composition):
SiO
2
45-86%
CaO
10-36%
P
2
O
5
 3-12%
Ag
2
O
 3-12%
Examples of preferred sol-gel derived bioactive glasses are shown below in Table 1, any of which can be modified to include an effective, anti-bacterial amount of silver ions using the methods described herein.
TABLE 1
Composition (mol. %) of bioactive gel-glasses.
Designation
SiO
2
CaO
P
2
O
5
49S
50
46
4
54S
55
41
4
58S
60
36
4
63S
65
31
4
68S
70
 26-
4
72S
75
21
4
77S
80
16
4
86S
90
 6
4
Higher CaO contents provide larger pore volumes and the onset of hydroxycarbonate apatite (HCA) deposition is accelerated. Gel-glasses with higher SiO
2
contents tend to have larger surface areas and exhibit higher growth rates of formation of an HCA layer.
Silver Salts
Any suitable silver salt can be used which can be incorporated into the bioactive glasses using a sol-gel method. Silver oxide is a preferred salt. Other suitable salts include silver nitrate, silver acetate, silver bromide and silver chloride. The amount of silver in the compositions is generally in the range of between about 0.1 and 12 percent by weight, preferably between about 3 and 12 percent by weight.
The toxicity limit for the ingestion of soluble silver salts i

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