Injectable paste based on bioactive glass

Abstract

Disclosed is an injectable paste based on bioactive glass, which can be injected easily through a syringe, and which results in minimum volume loss, for bone-filling operations.

Description

Injectable paste based on bioactive glass Field of invention

[0001] The invention relates to an injectable paste based on bioactive glass. State of the art

[0002] Bioactive glass compositions are widely used for bone filling and regeneration, particularly in orthopedic and dental surgery. The bone regeneration properties of bioactive glass have been known since the development of the first bioactive glasses by Larry Hench in the 1970s.

[0003] In bone surgery, bioactive glass is mainly used in 3 forms.

[0004] The first, in solid form, by filling a bone defect with bioactive glass granules. These granules are, for example, 45S5 bioactive glass granules, marketed in particular by the Noraker company. Other bioactive glass compositions are used in surgery in the form of granules, for example, S53P4 bioactive glass marketed by the Bonalive company.

[0005] The second, in the form of a malleable paste, allows the surgeon to shape the bone filling material before introducing it into the bone defect. Such pastes are obtained by mixing bioactive glass granules with a binder, so as to form a malleable paste. Patent US8288344 describes such a malleable paste. This paste comprises between 68% and 76% by weight of bioglass particles, and between 24% and 32% by weight of binder comprising a mixture of Glycerol and Polyethylene Glycol (PEG). As indicated in patent US8288344, such a malleable paste must be handled by the surgeon's gloves. This not only adds a step to the surgical operation, but also leads to a lack of precision in the application of the paste and a risk of contamination of the bone substitute.

[0006] In order to address the above-mentioned problems, patent EP2322134 describes a third form of use of bioactive glass in surgery, namely an injectable paste based on bioactive glass. Such a paste can be injected into the bone defect using a syringe, which avoids the step of handling the paste by the surgeon. The paste is injectable through a syringe with a diameter of less than 8 mm, which allows precise use by the surgeon to fill the bone defect. The injectable paste of patent EP2322134 comprises between 50% and 67% by weight of bioactive glass, a portion of the bioactive glass particles being in the form of spheres. The binder used comprises a mixture of PEGs of different molecular weights.The disadvantage of this injectable paste is that it leads to a significant loss of volume, because to make it injectable, it includes a volume of binder that is greater than the volume of the intergranular space between the bioactive glass particles. When the injectable paste is introduced into the bone defect, the binder is quickly resorbed, quickly leaving only the bioactive glass. The bioactive glass particles then pack down to leave only the intergranular space between them, which leads to a final filling volume of the bone defect much lower than the volume of injected paste. Tests have shown that with the paste of patent EP2322134, the loss of volume is at least 20%, which means that when the surgeon injects 10 cubic centimeters (cc) of injectable paste, only 8 cc of bone defect is filled. Another disadvantage is the relatively low weight percentage of bioactive glass in the injectable paste.Since the bioactivity, and therefore the biological utility, of a bioactive glass implant is linked to the concentration of bioactive glass in this implant, it is desirable to have the highest possible concentration of bioactive glass. Another disadvantage concerns the use of PEGs of different molecular weights in the binder, which makes the manufacturing process of such an injectable paste expensive and complex.

[0007] The object of the invention is to provide an injectable paste based on bioglass and binder, which is easily injectable in a syringe of small diameter, in particular less than 5 mm, which has a relatively high concentration by weight of bioglass to promote better bone reconstruction and which leads to a relatively low loss of volume after resorption of the binder, in particular less than 10%. Maintaining the volume after filling the defect means that the filling rate of the defect is maintained after release of the binders.

[0008] This object is obtained by an injectable paste comprising: between 72% and 76% by weight of bioactive glass; between 24% and 28% by weight of binder comprising glycerol and polyethylene glycol (PEG), the weight ratio of polyethylene glycol to glycerol being between 0.4 and 0.7; and in which the bioactive glass comprises: between 25% and 70% by weight of bioactive glass particles having a size distribution of 40 µm to 300 µm, at least 50% of said particles being spherical particles; between 30% and 75% by weight of bioactive glass particles having a size distribution of 300 µm to 710 µm, said particles being non-spherical particles.

[0009] Preferably, the injectable paste according to the invention comprises between 73% and 76% by weight of bioactive glass, preferably between 74% and 76% by weight of bioactive glass, preferably 75% by weight of bioactive glass.

[0010] Preferably the weight ratio of polyethylene glycol to glycerol is between 0.45 and 0.65.

[0011] Preferably, at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90% of the particles having a size distribution of 40 µm to 300 µm are spherical particles.

[0012] Preferably the bioactive glass comprises between 25% and 50% by weight of bioactive glass particles having a size distribution of 40 µm to 300 µm.

[0013] Preferably the PEG has a molecular weight of between 700 and 3000 g / mol, preferably between 1000 and 2500 g / mol, preferably 2000 g / mol. Description of embodiments of the invention

[0014] The invention relates to an injectable paste based on bioactive glass, which is injectable in a syringe with a diameter of less than 5 mm, which has a high concentration of bioactive glass (greater than 72%), and which leads to a minimal loss of volume (less than 10%) after resorption of the binder.

[0015] The inventors have surprisingly shown that a specific combination of factors (composition and percentage of binder, particle size, shape and percentage of bioactive glass particles) makes it possible to obtain these properties which are not all obtained at the same time in the state of the art.

[0016] The injectable paste formulations of the invention use spherical bioactive glass particles for particles with a particle size between 40 µm and 300 µm. The term "spherical" also means particles of substantially spherical shape, such as the substantially spherical particles described in patents EP2771041 and EP2322134, the objects of which are incorporated by reference with respect to the definition of substantially spherical particles. Methods for manufacturing substantially spherical particles are known to those skilled in the art. MO SCI, LLC, for example, provides bioactive glass particles in spherical form, in any particle size. However, the manufacture of spherical bioactive glass particles is expensive, so it is desirable to reduce the proportion of spherical particles in an injectable paste.Furthermore, this additional step entails an additional risk of contamination agent, so that the risk of contamination is higher when there are several types of spherical particles in the injectable paste. In the injectable paste according to the invention, only one type of spherical particles is present, namely particles with a particle size between 40 and 300 µm, so as to limit the risk of contamination of the final product.

[0017] Particles with a particle size between 300 µm and 710 µm are not spherical. This limits the cost of the injectable paste while limiting the risk of contamination linked to the manufacturing process for spherical particles between 300 µm and 710 µm.

[0018] In the following examples, the composition of the injectable paste is varied and certain parameters are measured to determine whether or not the paste is acceptable to a surgeon.

[0019] The first parameter is injectability. If the paste cannot be injected through a 5 mm diameter syringe, the paste is not acceptable.

[0020] The second parameter is the malleability and cohesiveness of the paste. If the paste is not malleable and does not hold together cohesively (paste with a granular appearance), it is impossible for the surgeon to use it precisely and is therefore not acceptable.

[0021] The third criterion is volume loss, i.e., the reduction in the volume of bioactive glass after binder resorption, compared to the volume of injected paste. This volume loss is expressed as a percentage. For example, if the volume of bioactive glass remaining after binder resorption is 9.5 cc, while the volume of injected paste was 10 cc, the volume loss is 5%. A volume loss greater than 10% is not acceptable because it does not provide sufficient guarantees, for both the patient and the surgeon, that the filling of the bone defect performed during the operation will remain the same postoperatively.

[0022] To determine the volume loss, the procedure is as follows. For a bioactive glass paste whose composition is known, a mixture of 10g of bioactive glass (without binder) according to this composition is prepared. This mixture is introduced into a graduated syringe and the corresponding volume is measured. Water is then introduced drop by drop into the syringe until the bioactive glass is covered. The volume of water introduced corresponds to the volume of the intergranular space between the bioactive glass particles. This volume of the intergranular space is then compared to the known volume of binder in the paste in question. For example, if the volume of bioactive glass is 6.5cc, the measured volume of water is 2.5cc while the volume of binder in the paste is 3cc, the volume loss is (3-2.5) / 6.5, or 7.7%.

[0023] The following examples use Noraker's 45S5 bioactive glass. However, identical results would be obtained with other bioactive glasses, as only the mechanical properties are tested, not the bioactivity properties. Example 1

[0024] A paste is prepared by mixing the following ingredients: 75% by weight of bioactive glass, distributed as follows: 25% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 75% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 25% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0025] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 0.1%, i.e. a negligible loss of volume. Example 2

[0026] Identical to example 1, but with the following binder composition: 7% by weight of PEG with a molecular weight equal to 2000 g / mol; 18% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.39.

[0027] The result is a paste that is neither malleable nor cohesive, and therefore not acceptable. Example 3

[0028] Identical to example 1, but with the following binder composition: 7.25% by weight of PEG with a molecular weight equal to 2000 g / mol; 17.75% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.41.

[0029] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 0.1%, i.e. a negligible loss of volume. Example 4

[0030] Identical to example 1, but with the following binder composition: 7.75% by weight of PEG with a molecular weight equal to 2000 g / mol; 17.25% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.45.

[0031] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 0.1%, i.e. a negligible loss of volume. Example 5

[0032] Identical to example 1, but with the following binder composition: 10.25% by weight of PEG with a molecular weight equal to 2000 g / mol; 14.75% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.69.

[0033] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 0.1%, i.e. a negligible loss of volume. Example 6

[0034] Identical to example 1, but with the following binder composition: 10.5% by weight of PEG with a molecular weight equal to 2000 g / mol; 14.5% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.72.

[0035] The result is a paste that is neither malleable nor cohesive, and therefore not acceptable. Example 7

[0036] A paste is prepared by mixing the following ingredients: 71% by weight of bioactive glass, distributed as follows: 25% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 75% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 29% by weight of binder, distributed as follows: 10% by weight of PEG with a molecular weight equal to 2000 g / mol; 19% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.53.

[0037] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 15%, which is not acceptable. Example 8

[0038] A paste is prepared by mixing the following ingredients: 72% by weight of bioactive glass, distributed as follows: 25% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 75% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 28% by weight of binder, distributed as follows: 10% by weight of PEG with a molecular weight equal to 2000 g / mol; 18% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0039] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 7%, which is acceptable. Example 9

[0040] A paste is prepared by mixing the following ingredients: 76% by weight of bioactive glass, distributed as follows: 25% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 75% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 24% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 15% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.6.

[0041] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 5%, which is acceptable. Example 10

[0042] A paste is prepared by mixing the following ingredients: 77% by weight of bioactive glass, distributed as follows: 25% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 75% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 23% by weight of binder, distributed as follows: 8% by weight of PEG with a molecular weight equal to 2000 g / mol; 15% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.53.

[0043] The result is a paste that is neither malleable nor cohesive, and therefore not acceptable. Example 11

[0044] A paste is prepared by mixing the following ingredients: 75% by weight of bioactive glass, distributed as follows: 20% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 80% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 25% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0045] We obtain a paste which cannot be injected through a 5mm diameter syringe, therefore not acceptable. Example 12

[0046] A paste is prepared by mixing the following ingredients: 75% by weight of bioactive glass, distributed as follows: 70% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 30% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 25% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0047] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 8%, which is acceptable. Example 13

[0048] A paste is prepared by mixing the following ingredients: 75% by weight of bioactive glass, distributed as follows: 75% by weight of bioactive glass particles, in spherical form, having a size distribution of 40 µm to 300 µm; 25% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 25% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0049] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 14%, which is not acceptable. Example 14

[0050] A paste is prepared by mixing the following ingredients: 75% by weight of bioactive glass, distributed as follows: 20% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 30% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 50% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 25% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0051] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 7%, which is acceptable. Example 15

[0052] A paste is prepared by mixing the following ingredients: 75% by weight of bioactive glass, distributed as follows: 25% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 25% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 50% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 25% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0053] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 9%, which is acceptable. Example 16

[0054] A paste is prepared by mixing the following ingredients: 75% by weight of bioactive glass, distributed as follows: 35% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 15% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 50% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm; 25% by weight of binder, distributed as follows: 9% by weight of PEG with a molecular weight equal to 2000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.56.

[0055] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 20%, which is not acceptable. Example 17

[0056] A paste is prepared by mixing the following ingredients:

[0057] 75% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0058] 25% by weight of binder, distributed as follows: 8% by weight of PEG with a molecular weight equal to 1500 g / mol; 17% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.47.

[0059] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 9%, which is acceptable. Example 18

[0060] A paste is prepared by mixing the following ingredients:

[0061] 76% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0062] 24% by weight of binder, distributed as follows: 8% by weight of PEG with a molecular weight equal to 1000 g / mol; 16% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.50.

[0063] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 8%, which is acceptable. Example 19

[0064] A paste is prepared by mixing the following ingredients:

[0065] 75% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0066] 25% by weight of binder, distributed as follows: 8% by weight of PEG with a molecular weight equal to 3000 g / mol; 17% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.47.

[0067] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 8%, which is acceptable. Example 20

[0068] A paste is prepared by mixing the following ingredients:

[0069] 75% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0070] 25% by weight of binder, distributed as follows: 7.25% by weight of PEG with a molecular weight equal to 1500 g / mol; 17.75% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.41.

[0071] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 9%, which is acceptable. Example 21

[0072] A paste is prepared by mixing the following ingredients:

[0073] 76% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0074] 25% by weight of binder, distributed as follows: 7% by weight of PEG with a molecular weight equal to 1000 g / mol; 17% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.41.

[0075] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 8%, which is acceptable. Example 22

[0076] A paste is prepared by mixing the following ingredients:

[0077] 75% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0078] 25% by weight of binder, distributed as follows: 7.25% by weight of PEG with a molecular weight equal to 3000 g / mol; 17.75% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.41.

[0079] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 8%, which is acceptable. Example 23

[0080] A paste is prepared by mixing the following ingredients:

[0081] 75% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0082] 25% by weight of binder, distributed as follows: 10.25% by weight of PEG with a molecular weight equal to 1500 g / mol; 14.75% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.69.

[0083] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 9%, which is acceptable. Example 24

[0084] A paste is prepared by mixing the following ingredients:

[0085] 76% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0086] 24% by weight of binder, distributed as follows: 9.75% by weight of PEG with a molecular weight equal to 1000 g / mol; 14.25% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.68.

[0087] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 9%, which is acceptable. Example 25

[0088] A paste is prepared by mixing the following ingredients:

[0089] 75% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0090] 25% by weight of binder, distributed as follows: 10.25% by weight of PEG with a molecular weight equal to 3000 g / mol; 14.75% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.69.

[0091] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 8%, which is acceptable. Example 26

[0092] A paste is prepared by mixing the following ingredients:

[0093] 76% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0094] 24% by weight of binder, distributed as follows: 7.70% by weight of PEG with a molecular weight equal to 1500 g / mol; 16.30% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.47.

[0095] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 7%, which is acceptable. Example 27

[0096] A paste is prepared by mixing the following ingredients:

[0097] 76% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0098] 24% by weight of binder, distributed as follows: 7.70% by weight of PEG with a molecular weight equal to 1000 g / mol; 16.30% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.47.

[0099] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 8%, which is acceptable. Example 28

[0100] A paste is prepared by mixing the following ingredients:

[0101] 76% by weight of bioactive glass, distributed as follows: 13% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 40 µm to 90 µm; 55% by weight of bioactive glass particles, in spherical form, having a size distribution of 90 µm to 300 µm; 32% by weight of bioactive glass particles, in non-spherical form, having a size distribution of 300 µm to 710 µm;

[0102] 24% by weight of binder, distributed as follows: 7.70% by weight of PEG with a molecular weight equal to 3000 g / mol; 16.30% by weight of glycerol (gly), i.e. a PEG / gly ratio of 0.47.

[0103] A malleable and cohesive paste is obtained, injectable through a 5mm diameter syringe. The loss of volume, measured according to the method described above, is 6%, which is acceptable.

Claims

An injectable paste comprising:between 72% and 76% by weight of bioactive glass;between 24% and 28% by weight of binder comprising glycerol and polyethylene glycol (PEG), the weight ratio of polyethylene glycol to glycerol being between 0.4 and 0.7;and wherein the bioactive glass comprises:between 25% and 70% by weight of bioactive glass particles having a size distribution of 40 µm to 300 µm, at least 50% of said particles being spherical particles;between 30% and 75% by weight of bioactive glass particles having a size distribution of 300 µm to 710 µm, said particles being non-spherical particles,and wherein the PEG has a molecular weight of between 1000 and 3000 g / mol. Injectable paste according to claim 1, in which the proportion by weight of bioactive glass is between 73% and 76%, preferably between 74% and 76%, preferably equal to 75%. Injectable paste according to one of the preceding claims, in which the weight ratio of polyethylene glycol to glycerol is between 0.45 and 0.

65. Injectable paste according to one of the preceding claims, wherein at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90% of the particles having a size distribution of 40 µm to 300 µm are spherical particles. An injectable paste according to any preceding claim, wherein the bioactive glass comprises between 25% and 50% by weight of bioactive glass particles having a size distribution of 40 µm to 300 µm. Injectable paste according to one of the preceding claims, in which the PEG has a molecular weight of between 1000 and 2000 g / mol, preferably 2000 g / mol.