KR20160115878A - putty carrier loading the particular bone graft material - Google Patents

Abstract

The present invention relates to a putty carrier composition including cross-linked alginic acid and carboxymethyl cellulose (CMC) as a main ingredient. The putty carrier composition including a particular content of cross-linked alginic acid and CMC can be in a shape maintained without losing the properties of stabilized viscous gel. Provided is a putty carrier of a granular bone transplanting material, wherein the putty carrier can be useful in reproducing bone tissue by making a bone transplantation powder, a growth factor, or a drug continuously remain in a local region without being easily diluted in blood.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a particulate bone graft material,

The present invention relates to a putty carrier composition comprising, as a main component, crosslinked alginic acid and carboxymethyl cellulose (CMC).

Bone graft material is used to fill the space in bone tissue and to promote the formation of new bone when bone defect is created due to disease or trauma. Bone graft materials may contain organic substances such as growth factors and bone formation proteins in order to increase bone forming ability in addition to bone materials as inorganic substances.

However, the bone graft material filled in the bone defect site is exposed to systemic blood, so that the granular bone material and the growth factor flow out and the effective concentration in the local region is not maintained, and the bone graft material itself is difficult to maintain its shape and stay .

To solve this problem, gelatin, glycerol, poloxamer, hyaluronic acid, alginic acid, and carboxymethylcellulose, which are biocompatible and absorbable, have the advantage of imparting viscosity. However, although these polymers have a viscosity, they are easily diluted in the blood, which disadvantageously can not completely prevent the bone graft material or the growth factor from flowing down.

Korean Patent No. 1,443,814 has suitable biocompatibility and physical properties and uses a hydrogel containing a certain amount of a combination of poloxamer and hydroxypropylmethyl cellulose (HPMC) and a calcium phosphate compound particle to maintain the formulation Which is capable of maintaining a gel shape well in a body temperature region by mixing with hydroxypropylmethylcellulose at a certain amount and exhibiting a shape retaining property after implantation.

However, there is still a lack of research and development on the composition of the gel to keep the bone formation ability of the bone graft material and the drug for prevention of infection stably in the body through the gel.

Therefore, there is a demand for the development of a putty-like carrier composition which has suitable biocompatibility and physical properties for bone graft materials and which is capable of maintaining shape without being easily diluted in blood.

Korean Patent No. 1,443,814

It is an object of the present invention to provide a putty carrier composition of particulate bone graft material which is not easily diluted in water but has putty properties.

In order to accomplish the above object, the present invention provides a method for producing alginic acid by cross-linking alginic acid with a calcium salt such as calcium chloride and forming a cellulosic carbomethyl cellulose (CMC) The present invention provides a putty carrier composition comprising a crosslinked alginic acid and CMC as main components and a method for producing the same, wherein the coupling is made in all the volumes and prevents the plasticity from disappearing.

The present invention provides a putty carrier comprising a crosslinked alginic acid and carbomethyl cellulose (CMC) as a main component in a predetermined amount, whereby the bone graft material powder, growth factor or drug is not easily diluted in the blood, So that it can be usefully used for bone tissue regeneration.

1 is a photograph of a lyophilized block type putty bone graft material according to the present invention.
Figure 2 is a photograph of a lyophilized mandibular putty bone graft material according to the present invention.
FIG. 3 is a photograph of putty bone graft material obtained by hydrating a freeze-dried putty bone graft material according to the present invention and restoring the properties of the putty.
FIG. 4 is a photograph of a putty bone graft material according to the present invention in which no dilution or particle separation is observed even when immersed in water for 1 hour.
5 is a photograph of a lyophilized putty sponge according to the present invention.
Figure 6 is a photograph of a lyophilized putty sponge after immersion in a solution of calcium chloride and rhBMP-2 according to the present invention.
FIG. 7 is a photograph of a putty sponge according to the present invention in which no dilution or particle separation is observed even when immersed in water for 1 hour.

The present invention relates to a putty carrier composition comprising (a) a step of mixing alginic acid powder, alginic acid crosslinking agent and carboxymethylcellulose powder to prepare a homogeneous mixture powder, and (b) kneading the mixture powder with distilled water to knead And a method for producing the same.

In one embodiment of the present invention, the crosslinking agent of alginic acid in the above production method may be a calcium salt.

In one embodiment of the present invention, the alginic acid powder and distilled water may be contained in an amount of 0.1 to 0.9 parts by weight and 0.1 to 5 parts by weight based on 1 part by weight of the whole mixture powder.

In one embodiment of the present invention, in the step (a), the absorbent polymer may be further added in an amount of 0.01 to 0.5 parts by weight based on 1 part by weight of alginic acid powder.

In one aspect of the present invention, the absorbent polymer that may be further included is selected from the group consisting of polycaprolactone (PCL), polylactic acid (PLA), polylactic glycolic acid (PLGA), polyglycolic acid (PGA), chitosan, collagen, And mixtures of two or more thereof.

The present invention relates to a putty carrier composition comprising, as a main component, crosslinked alginic acid and carboxymethylcellulose.

In one embodiment of the present invention, alginic acid which is contained as a main component in the putty carrier composition may be crosslinked by a calcium salt.

In one embodiment of the present invention, the putty carrier composition may contain alginic acid in an amount of 0.01 to 0.9 parts by weight based on 1 part by weight of the whole mixture powder.

In one embodiment of the present invention, the putty carrier composition may further include an absorbent polymer in an amount of 0.01 to 0.5 parts by weight based on 1 part by weight of the alginic acid powder. The absorbent polymer that may be further included includes polycaprolactone (PCL), poly It may be a mixture of one or more kinds selected from the group consisting of lactic acid (PLA), polylactic glycolic acid (PLGA), polyglycolic acid (PGA), chitosan, collagen and hyaluronic acid.

In one aspect of the invention, the putty carrier composition may be in the form of a sheet, a porous sheet, a sponge, a jellied, a gel, a microsphere, a tubular, a tube, a lattice, And can be processed into any one form selected from the group consisting of dried form.

In one aspect of the present invention, the putty carrier composition may further comprise at least one member selected from the group consisting of a granular bone graft material, a growth factor, and a topically acting drug, Component. ≪ / RTI >

In one aspect of the present invention, the granular bone graft material is selected from the group consisting of synthetic bone, allogeneic bone, heterogeneous bone, demineralized bone, tricalcium phosphate (TCP), monocalcium phosphate, tetracalcium phosphate, dicalcium phosphate, hydroxyapatite, Or a mixture of two or more kinds selected from the group consisting of materials.

In one aspect of the invention, the growth factor is selected from the group consisting of BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP- , Bone morphogenetic protein (BMP) selected from BMP-13, an amino acid binding complex of the amino acids constituting the same, a hepatocyte growth factor, a fibroblast growth factor, A growth factor, a TGF-beta superfamily factor, a platelet-derived growth factor, an insulin-like growth factor, an epithelial growth factor, a translational growth factor, a keratinocyte growth factor 2 (KGF2) A recombinant protein, and a recombinant protein.

In one embodiment of the present invention, the topically acting drug may be one or a mixture of at least one member selected from the group consisting of antiinflammatory agents, antimicrobial agents, and adrenocorticotropic agents, but the kind of drugs that may be included is not limited thereto .

In one embodiment of the present invention, the anti-inflammatory analgesic may be nonsteroidal antiinflammatory drugs (NSAIDs), diclofenac or indomethacin, and NSAIDs specifically include Piroxicam, ketoprofen, , Phenylpropionic acid derivatives including flurbiprofen, fenoprofen, ibuprofen, and the like; But are not limited to, oxicam derivative derivatives including piroxicam, tenoxicam, and meloxicam.

In one aspect of the invention, the antimicrobial agent is selected from the group consisting of amoxicillin, erythromycin, metronidazole, amoxacillin-clavulanate, Ampicillin-sulbactam, Ampicillin ), Piperacillin, Benzathine penicillin, Cephalosporin, Cefazolin, Lincosamide, Clindamycin, Macrolide, tetracycline hydrochloride , Cetylpyridinium chloride, chlorhexidine hydrochloride, but are not limited thereto.

In one aspect of the invention, the adrenocorticotropic agent may be methylprednisolone or hydrocortisone acetate, but is not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to the following examples. It should be understood, however, that the same is by way of illustration and example only and is not intended to limit the scope of the present invention.

[Example]

Example 1: Preparation of putty bone graft material containing granular bone graft material

10 g of synthetic bone graft material particles consisting of a combination of tricalcium phosphate (TCP) and hydroxyapatite, 1 g of alginic acid powder, 0.2 g of calcium chloride powder and 1 g of carboxymethyl cellulose (CMC) The mixture was homogeneously dispersed with stirring for a minute and then put into a kneader. 10 g of distilled water was added to the mixture put into the kneader and kneaded for 30 minutes to prepare a putty-type bone graft material.

This was filled in a mold having a block-shaped groove and lyophilized to form a block-type putty bone implant which prevents the viscosity from decreasing even in gamma sterilization (Fig. 1). The syringe was filled with a putty-type bone graft material and lyophilized to form a putty-type graft implant (Fig. 2).

It was confirmed that the bone graft material prepared by hydrating the lyophilized bone graft material recovered the putty property by hydration (Fig. 3). Even if the bone graft material recovered from the putty property was stored for 1 hour in water, (Fig. 4).

Example 2: Preparation of putty sponge containing animal cell-derived recombinant bone formation protein (rhBMP-2)

1 g of alginate powder and 1 g of carbomethyl cellulose (CMC) powder were homogeneously dispersed in a mixer for 10 minutes and then added to a kneader. 10 g of distilled water was added to the mixture put in the kneader, and the mixture was kneaded for 30 minutes to prepare a liquid. The mixture was put into a glass ampoule, lyophilized, processed with a sponge, and then subjected to gamma sterilization (FIG. The prepared sponge was moistened with a mixture of 3% calcium chloride solution and 50 rhBMP-2 to induce crosslinking reaction of alginic acid to encapsulate rhBMP-2, followed by lyophilization to prepare a putty sponge containing rhBMP-2 6).

It was confirmed that the prepared sponge was not diluted or absorbed even if it was kept in water for 1 hour (Fig. 7).

Claims (1)

Wherein said alginic acid is crosslinked at its entirety by a calcium salt. 2. A putty carrier composition according to claim 1, wherein said alginic acid is crosslinked by calcium salt.

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