WO1985001210A1

WO1985001210A1 - Biodegradable implant

Info

Publication number: WO1985001210A1
Application number: PCT/GB1984/000309
Authority: WO
Inventors: Laslo Juhasz
Original assignee: The University Of Strathclyde
Priority date: 1983-09-10
Filing date: 1984-09-10
Publication date: 1985-03-28
Also published as: GB8324276D0; EP0155288A1

Abstract

A biodegradable implant is manufactured from a biodegradable glass material which contains a glass forming material and one or more metal oxides, the glass forming material being phosphorous pentoxide and alumina, and a metal oxide. The ratio of metallic elements in the glass is substantially the same as in the tissue into which the implant is to be implanted. This reduces the chance of rejection of the implant by the body. The glass may be produced in the form of a foamed body to provide a bone substitute.

Description

BIODEGRADABLE IMPLANT

This invention relates to a biodegradable implant for human or animal use.

It is known that certain glass-like and ceramic materials are biocompatible with the human and animal body and some of these materials are known to be soluble in bodily fluids and are tolerated by the body fluids and tissue without causing an immunological reaction which could otherwise result in rejection and subsequent expulsion of the implant by the body. Such materials are useful in the manufacture of, for example, pros- theses. The principal aim of research on these mater¬ ials has been to produce bone substitutes. To provide the necessary physical and mechanical properties it has normally been necessary to incorporate additional re- inforcing materials such as plastics. The main thrust of continuing research in this field is to produce pros- theses from these glasses and ceramics.

An object of the present invention is to provide a biodegradable implant which will dissolve in body fluids at a predeterminable rate.

According to the present invention there is provided a biodegradable implant of which the material of manu¬ facture is a biodegradable glass comprising a glass- forming or modifying component and a biocompatible metal oxide in which the ratio of the metallic elements in the glass are in substantially the same ratio as in the tissue in contact with which the implant is to be located.

Preferably the glass also contains an amount of a physiologically benign processing additive and/or a chemotherapeutic agent.

The chemotherapeutic agent may be, for example, a free metal selected from zinc, copper, silver, gold and platinum and mixtures thereof, preferably in a concen¬ tration of from 1 to 10 %. Preferably the glass-forming/modifying component is phosphorus pentoxide and alumina and the ratio of glass- former to metal oxide in the glass is from 1:3 to 3:1. The glass preferably contains no more than five mole percent of alumina.

To produce a bone substituting material the glass may be produced by fusion in the presence of an amount of a gas-releasing foaming agent such as an inorganic carbonate or bicarbonate. The implant may be produced by casting of the glass in the molten state in a mould or by machining a body of the glass using ordinary techniques.

When the glass is produced by fusion of a mixture of the powdered components in a platinum crucible under an inert atmosphere the fusion occurs at around 1100 to 1300°C. The melt may be cast bypouring into moulds, extrusion to give tubes, ground to a powder or formed into beads. Conventional glass fabrication and hand¬ ling techniques are applicable. Powdered glass may be further processed to produce other forms, for example, as follows:

1. A sintered glass may be made by forming glass pow¬ der into a slurry with liquid, normally water, and subjecting the slurry to pressure and heat to form a compact mass. This step may conveniently be done at a pressure of from 5 to 20 tons and a tem¬ perature of around 350°C for 10 to 30 minutes. The compact mass is then fired in a furnace at a temperature of from 700 to 900°C for from 5 to 10 minutes.

The glass so produced may have a tensile strength of from 20 to 40 MPa and a compression of from 200 to 400 MPa. It is useful as a bone substitute: real bone has a tensile strength of around 196 MPa. 2. By incorporating into the powdered glass a propor- tion of a foaming agent, that is a substance which liberates gas at the fusion temperature and may be, for example, calcium or sodium carbonate, a glass may be produced in a foamed form. The pore size distribution may be around 100 to 200 microns but can be varied by varying the particle size of the powdered components. A quantity of ground and screened glass is mixed with a quantity (from 0.01 to 2.00 % by weight) of calcium carbonate or other suitable foaming agent in a porcelain crucible or a mould and heated to a temperature to fuse the glass and to liberate the foaming gas. A tempera¬ ture of from 600 to 700°C is sufficient. The foamed mass is allowed to cool to give a porous body which can be further fabricated to shape by grinding and milling etc.. The foamed glass thus produced is not structurally strong. 3. Porous glass, which has a greater in structural strength than the foamed glass described in the foregoing paragraph may be produced by a modifi¬ cation of the foamed glass production process. A mix may be made up as described above but the mix then slurried with water. The foaming agent may be a carbonate as described before or hydrogen peroxide. The slurry is heated at from 100 to 180°C for from 15 to 20 minutes and then placed in a mould or crucible and fired at 600 to 700°C for from 10 to 30 minutes. The porous body so produced has a smaller pore size than the foamed glass (from 10 to 30 microns) and consequently greater strength. The porous glass is also useful as a bone substitute. Inorganic chemotherapeutic agents may be incorporated into the glass simply by fusing them along with the other powder components of the mix. One particular area of interest is the use of colloidal metals such as zinc,_.- copper, silver gold and platinum. The therapeutic use of these metals are already known: the present invention provides a convenient method of delivering them to the affected site in very finely divided form and releasing them from the glass over a long period of time which is deter¬ mined by the rate of dissolution of the glass in the body. Fine beads of glass may be formed by conventional glass fabrication techniques and may be directly injected to the affected sites.

In addition, fine needles of the glass may be inser¬ ted through the skin of a patient directly to the site. One advantage of this technique is that the progress of the needle into the body may be mon¬ itored very easily under X-ray, since all the glasses are radio-opaque.

Ground powders or fine beads of the glass provide a convenient form for direct topical application to wound management when therapeutic metals are used.

The bone substitutes of this invention are of par¬ ticular importance. Particular examples of the use are: (a) delayed and non-union fractures,

(b) arthrodesis of joints,

(c) filling of cavities in bone,

(d) replacement of bone and joint loss,

(e) augmentation of acetabulum and cranium, (f) fusion of growth-plate cartilages,

(g) arthrosis of joints (bone-block operations) (h) bone and muscle transfer for ligamentous defects. The rate of dissolution of the glasses which are used in this invention can be readily adjusted and it is herein that the main advantage of their use lies. By adjusting the rate of solubility to a preselected value the glass will remain in the body for that time and there are many surgical and medi- cal applications where this property can be of great advantage. In concise terms, the rate of dissolu¬ tion is altered by altering the ratio of the glass- former to the metal oxide.

The following examples illustrate the invention. Example 1

Moulded biodegradable glass having a typical composition: 44% phosphorus pentoxide, 18% sodium oxide, 1% alumina, the remainder being calcium oxide, is used as a spacer or joint resurfacer in surgery on arthritic joints. Patients suffering from rheumatoid arthritis of the hand in whom the disease has progressed to the extent of des¬ truction of the articular cartilage but not to disrup¬ tion of the joint or bone erosion, may be treated by re¬ construction of the cartilage by means of a perichondral graft. The two articular surfaces covered by the graft have to be physically separated for a period of from four to six weeks. This has been traditionally achieved by a silastic rubber spacer which had to be removed in a second operation. Biodegradable glass spacers are ideally suited to this clinical application and can be moulded to conform to the required shape and with a pre¬ determined dissolution rate. This obviates the need for the second operation as it dissolves away leaving no residues. Current methods of treating end-stage arthritis are centred around the replacement of joints, for example the hip joint, by passive prostheses. This produces accep¬ table results in elderly patients. However, this approach does not provide an ideal solution in young patients in whom loosening, infection and bone resorption

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Resurfacing of the hip joint with biodegradable glass provides a biological solution for young patients by facilitating regeneration and repair of the cartilage surface. It will direct the replacement of damaged ar¬ ticular surface cartilage, permit early post-operative motion and protect young cartilage cells until a stable matrix is formed by ^"these cells. After a period of time this temporary glass prosthesis will completely dissolve away and provide a functional joint surface. Example 2

By incorporating therapeutic mineral elements such as zinc silver, copper, gold and platinum into the glass during preparation the glass will release these materials in quantity and at a rate over a period of time. For example, copper plays a therapeutic role in acute and chronic inflammation, gold is believed to inhibit lyo- somal enzymes responsible for joint destruction and silver and zinc are known therapeutics for burns and other surgical wounds. One of the practical advantages of the use of these biodegradable glasses in powder and granular form is that they can provide localised treat¬ ment or be implanted adjacent to diseased tissue.

A typical glass composition for these purposes is: 30% phosphorus pentoxide, 4.8% potassium oxide, 3.6% zinc oxide and 1% alumina, the remainder being sodium oxide. This dissolution time is around two to three weeks. Example 3

Tubes made of the glasses serve as temporary ducting in various vessels after surgery such as blood vessels, bile duct, ureter and vas deferens. These tubes are inserted into the cut ends of the vessels and the ends are then stitched together around the outside of the tube. As the surgical stitching heals and the vessel ends unite the internal tubing dissolves thus avoiding the need for second surgical intervention as is presently done using silicone rubber shunts. A typical glass for this use has the composition: 44% phosphorus pentoxide, 40% sodium oxide, 1.3% potassium oxide, 1% alumina the re- mainder being calcium oxide. Example 4

Foamed Biodegradable glass is useful as a bone substitute for treating bone defects as a result of disease or surgery as its porous nature encourages tis- sue growth and acts as dynamic scaffolding. Inorganic ions enhance healing and stimulate bone formation leaving the regenerated natural bone behind. Important areas of application are orthopaedic and craniofacial surgery when it is difficult to obtain sufficient autogenous bone, particularly in veryyoung patients. A typical composition for such uses is: 62% phosphorus pentoxide, 1% alumina, 1.5% sodium oxide the remainder being calcium oxide. Sodium carbonate at a level of 1% is incorporated into the mix prior to fusion to cause the molten glass to foam.

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OMPI

Claims

CLAIMS :

1. A biodegradable implant of which the material of manufacture is a biodegradable glass comprising a glass- forming/modifying component and a bioca patible metal oxide characterised in that the ratio of metallic ele- ments in the glass are in substantially the same ratio as in the tissue in which the implant is to be located.

2. An implant as claimed in claim 1, containing also an amount of a physiologically benign processing addi¬ tive and/or a chemotherapeutic material.

3. An implant as claimed in claim 1 or claim 2, in which the chemotherapeutic material is an elementary metal selected from zinc, silver, gold, copper and pla¬ tinum in an amount of from 1 to 10 percent.

4. An implant as claimed in any preceding claim, in which the glass-forming/modifying component is a mixture of phosphorus pentoxide and alumina.

5. An implant as claimed in claim 4, in which the ratio of glass-forming/modifying component to the metal oxide is from 1:3 to 3:1.

6. An implant as claimed in claim 4 or claim 5, in which the glass contains no more than five mole percent of alumina.

7. An implant as claimed in any preceding claim, in which the glass is formed by fusion in the presence of a gas-releasing foaming agent to produce a foamed glass.

8. An implant as claimed in claim 7, in which the foaming agent is an inorganic carbonate or bicarbonate.

9. An implant as claimed in any preceding claim which is produced by casting of molten glass in a mould.

10. An implant as claimed in any one of claims 1 to 8, which is produced by forming a slurry of powdered glass in a liquid, pressing and heating the slurry in a mould to form a compact mass and firing the moulded mass.

11. An implant as claimed in claim 10, in which the slurry is pressed at a compression of from 5 to 20 tons at about 350°C for from 5 to 10 minutes and the firing is conducted at a temperature of from 700 to 900°C for from 5 to 10 minutes.

12. An implant as claimed in any of claims 1 to 8, in which powdered glass and a foaming agent are mixed toget¬ her in a slurry with a liquid, the slurry is preheated at a temperature of from 100 to 180°C for from 15 to 20 minutes, placed in a mould or crucible and fired for from 10 to 30 minutes at a temperature of from 600 to 700°C.

13. An implant as claimed in claim 12, in which the foaming agent is calcium carbonate or sodium bicarbonate or hydrogen peroxide.

OMPI

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