CN109810440A - A kind of PMMA/SCTP composite fine powder and preparation method and composite bone cement using the same - Google Patents

Abstract

The invention relates to a PMMA/SCTP composite micropowder with a core-shell structure. The core is methyl methacrylate copolymer (PMMA) and the shell is sodium calcium tripolyphosphate (SCTP). The preparation steps of the composite microspheres are to prepare the copolymer microspheres first, and then deposit and coat the sodium calcium tripolyphosphate on the surface of the copolymer microspheres under the action of the template agent to obtain the PMMA/SCTP composite micropowder. The composite micropowder is used to prepare composite bone cement.

Description

A kind of PMMA/SCTP composite micropowder and preparation method and composite bone using the same cement

technical field

The invention relates to an organic/inorganic nano-powder with a core-shell structure, in particular to a PMMA/SCTP composite fine powder, a preparation method of the composite fine powder, and a composite bone cement prepared by using the same.

Background technique

Bone cement is a biomaterial that is used to fill bone or implant into bone spaces or cavities and has self-coagulating properties. Bone cement mainly includes polymethyl methacrylate (PMMA) bone cement and calcium phosphate bone cement. Among them, PMMA bone cement has achieved good clinical application results, but PMMA itself is biologically inert and cannot be combined with bone tissue. In contrast, calcium phosphate-based bone cements are biocompatible, biodegradable, close to bone tissue in composition, and can promote osseointegration, cell adhesion, and new bone formation.

Patent CN1927416 relates to a composite porous calcium phosphate bone cement and its preparation method. The bone cement is composed of calcium phosphate bone cement solid phase powder, 3-hydroxybutyric acid-co-3-hydroxyvaleric acid copolymer (PHBV) microspheres and curing liquid treated with 60Co rays. Patent CN101716379 relates to a dual-curing composite calcium phosphate bone cement including a solid phase and a liquid phase. The solid phase includes calcium phosphate bone cement powder and an oxidizing agent; the liquid phase includes deionized water, a water-soluble cross-linkable polymer, and a reducing agent. Patent CN1821143 provides a preparation method of calcium phosphate bone cement composite material. (1) Calcium phosphate, calcium carbonate and calcium hydrogen phosphate are synthesized by high-temperature solid-phase reaction to synthesize powder containing only hydroxyapatite and α-tricalcium phosphate. (2) prepare acrylic acid-itaconic acid copolymerization liquid, as liquid phase; (3) take solid phase and liquid phase by weight ratio 3: 1, mix, fill in mould forming, in calcium phosphate bone cement reconciling process in The human gene recombinant bone morphogenetic protein-2 is incorporated into each mold to obtain a calcium phosphate bone cement material compounded with BMP-2.

Patent CN105315478 relates to a kind of copolymer with nano-calcium phosphate coating polymethyl methacrylate (PMMA) as the base and its coating method. The method includes synthesizing PMMA-based copolymer microspheres containing hydroxyl side groups, reacting calcium salt and phosphoric acid solution with the hydroxyl side groups on the PMMA-based copolymer microspheres, and making PMMA-based polymer microspheres on the PMMA-based polymer microspheres. thickening of the nanocalcium phosphate coating.

SUMMARY OF THE INVENTION

The invention provides a PMMA/SCTP composite micropowder, the composite micropowder has a core-shell structure, the core is a copolymer microsphere of methyl methacrylate (MMA), a functional monomer and a cross-linking agent, and the shell is It is sodium calcium tripolyphosphate (SCTP).

In another aspect, the present invention provides a method for coating PMMA copolymer microspheres with SCTP. Firstly, PMMA copolymer microspheres are synthesized, and then calcium chloride and sodium tripolyphosphate are reacted, and aggregated and coated on PMMA copolymer microspheres under the action of a template to obtain PMMA/SCTP composite micropowders.

Furthermore, the present invention provides a composite bone cement using the PMMA/SCTP composite fine powder.

A kind of PMMA/SCTP composite micropowder of the present invention, its preparation method comprises the following steps:

(1) Prepare a composite emulsifier, prepare a mixed monomer, and at the same time prepare an aqueous potassium persulfate solution with a concentration of 0.1% to 10%;

The composite emulsifier includes sodium dodecyl sulfate, sodium dodecyl sulfonate, sodium dodecyl benzene sulfonate, sodium diisooctyl succinate, OP series emulsifier, Tween series emulsifier , one or any combination of Span series emulsifier, polyvinyl alcohol, carboxymethyl cellulose;

The mixed monomer includes methyl methacrylate, functional monomer and cross-linking agent, wherein the weight ratio of methyl methacrylate, functional monomer and cross-linking agent is 1:0.05-0.2:0.001-0.1;

The functional monomers are hydroxymethyl acrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxybutyl acrylate, hydroxymethyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methyl acrylate One or any combination of base acrylate, hydroxybutyl methacrylate, and the crosslinking agent is one of triethylene glycol bismethacrylate, bisphenol A-glycidyl bismethacrylate. kind;

(2) Add 100 parts of deionized water, 0.5 to 10 parts of composite emulsifier, and 6 to 30 parts of mixed monomers in sequence into the reactor, heat up and emulsify at the same time, and protect with nitrogen; Part to 1 part of potassium persulfate aqueous solution, after 15min to 60min of reaction, 20 to 90 parts of mixed monomer and 0.1 to 2 parts of potassium persulfate solution are added dropwise at the same time within 2h to 3h; after the dropwise addition, continue to keep warm The reaction is carried out for 2h to 3h; the temperature is lowered to room temperature, and several cycles of centrifugal separation and deionized water washing are carried out to obtain methyl methacrylate copolymer microspheres;

The diameter of the methyl methacrylate copolymer microspheres is between 0.02 μm and 3 μm.

(3) At room temperature, add 100 parts of deionized water, 1 to 20 parts of methyl methacrylate copolymer microspheres, and 0.2 to 4 parts of templating agent in sequence, stir until dissolved, adjust with sodium hydroxide pH value reaches 7.5～8.5; add calcium chloride aqueous solution, after stirring for 15min～45min, add sodium tripolyphosphate aqueous solution according to the molar ratio of calcium element and sodium element as 2:1, react for 0.3h～2h, and age for 1h～2h , filtered, washed with ethanol, and freeze-dried to obtain PMMA/SCTP composite micropowder;

The templating agent is tyrosine, glycine, aspartic acid, glutamic acid, 6-aminocaproic acid, maltodextrin, EDTA, disodium EDTA, EDTA tetra a type of sodium;

The particle size of the PMMA/SCTP composite micropowder is between 0.02 μm and 200 μm; and the sodium calcium tripolyphosphate can continue to be deposited on the surface of the microsphere.

A composite bone cement is prepared by using the PMMA/SCTP composite fine powder. The composite bone cement is composed of a powder part and a liquid part, and the powder part consists of 65 to 75 parts of the PMMA/SCTP composite micropowder, 0.1 to 3 parts of an initiator and 24 to 32 parts of barium sulfate The liquid part is uniformly mixed by mixing 90 to 99.5 parts of methyl methacrylate, 0.5 to 10 parts of an accelerator and 60 to 200 ppm of hydroquinone.

Described initiator is a kind of in benzoyl peroxide, dilauroyl peroxide;

Described accelerator is a kind of in N,N-dimethyl-p-toluidine, N,N-dimethylaniline, N-methyl-N-(2-hydroxyethyl)-p-toluidine .

The powder part and the liquid part are separately packaged in sterile containers after aseptic treatment, and mixed according to the weight ratio of the powder part to the liquid part of 1.5-4:1 before use.

The PMMA copolymer contains hydrophilic hydroxyl groups. Under the action of the template agent, calcium ions and tripolyphosphate ions combine to settle on the surface of the PMMA copolymer microspheres, and then aggregate and coat. After separation, washing, and freeze-drying, the formation of PMMA/SCTP composite powder. SCTP has biocompatibility and activity, and as the main component, it can impart biological activity to bone cement.

specific embodiment

Example 1

The composite emulsifier of sodium dodecylbenzene sulfonate, OP-10 and polyvinyl alcohol was prepared according to the weight ratio of 1:1:0.15; methyl methacrylate, hydroxyethyl methacrylate were prepared according to the weight ratio of 1:0.1:0.02 Mixed monomers of methacrylate and triethylene glycol bismethacrylate; prepare a potassium persulfate aqueous solution with a concentration of 1%.

Mix 100 parts of deionized water, 4.5 parts of compound emulsifier, and 15 parts of mixed monomers, start stirring, and heat up at the same time to form an emulsion, adjust the pH value to 8 with ammonia water, and fill with nitrogen for protection; heat up to 80 ° C for 15 minutes 6 parts of potassium persulfate solution was added dropwise, and after 30 minutes of reaction, 30 parts of mixed monomer and 12 parts of potassium persulfate solution were added dropwise at the same time within 2 hours; after the dropwise addition, the reaction was continued for 3 hours. The temperature was lowered to room temperature, and three cycles of centrifugal separation and 1000 parts of deionized water were performed to obtain methyl methacrylate copolymer microspheres. Using scanning electron microscopy, the average particle size of the methyl methacrylate copolymer microspheres was measured to be 32.7 nm.

Add 100 parts of deionized water, 5 parts of methyl methacrylate copolymer microspheres, 0.5 part of L-glutamic acid to the reaction kettle in turn, stir until dissolved, adjust the pH to 8 with sodium hydroxide; add 10 parts of concentration It was 50% calcium chloride aqueous solution, stirred for 20min, added 8.3 parts of 50% sodium tripolyphosphate aqueous solution, reacted for 1.5h, aged for 1.5h, filtered, washed with ethanol, and freeze-dried to obtain PMMA/SCTP composite micropowder; The average particle size of the PMMA/SCTP composite micropowder was measured to be 108 nm by scanning electron microscopy.

Mix 73 parts of PMMA/SCTP composite micropowder, 2 parts of benzoyl peroxide, and 25 parts of barium sulfate as powder part; 96.4 parts of methyl methacrylate (containing 100ppm of hydroquinone), 3.6 parts of N, The N-dimethyl-p-toluidine was mixed well and used as the liquid part. Sterilize separately, take the powder part and the liquid part according to the ratio of 3:1, and store them in sterile cryopreservation tubes respectively.

Example 2

The composite emulsifier of sodium lauryl sulfate and Span-60 is prepared according to the weight ratio of 1:1.5; methyl methacrylate, hydroxyethyl acrylate and ethyl dimethacrylate are prepared according to the weight ratio of 1:0.2:0.01 Mixed monomer of glycol ester; prepare potassium persulfate aqueous solution with concentration of 1%.

Mix 100 parts of deionized water, 3 parts of compound emulsifier, and 5 parts of mixed monomers, start stirring, and heat up at the same time to form an emulsion, adjust the pH value to 8 with ammonia water, and fill with nitrogen for protection; heat up to 80 ° C for 15 minutes 6 parts of potassium persulfate solution was added dropwise, and after the reaction for 30 minutes, 55 parts of mixed monomers and 10 parts of potassium persulfate solution were added dropwise simultaneously within 2 hours; after the dropwise addition, the reaction was continued for 3 hours. The temperature was lowered to room temperature, and three cycles of centrifugal separation and 1000 parts of deionized water were performed to obtain methyl methacrylate copolymer microspheres. Using scanning electron microscopy, the average particle size of the methyl methacrylate copolymer microspheres was measured to be 0.46 μm.

Add 100 parts of deionized water, 5 parts of methyl methacrylate copolymer microspheres, and 1 part of disodium EDTA into the reaction kettle in turn, stir until dissolved, and adjust the pH to 8 with sodium hydroxide; add 25 A calcium chloride aqueous solution with a concentration of 50% was added into 21 parts of an aqueous solution of sodium tripolyphosphate with a concentration of 50% after stirring for 20 min, reacted for 2 h, aged for 2 h, filtered, washed with ethanol, and freeze-dried to obtain the PMMA/SCTP composite micropowder; Using scanning electron microscopy, the average particle size of the PMMA/SCTP composite micropowder was measured to be 2.59 μm.

Mix 70 parts of PMMA/SCTP composite micropowder, 2 parts of benzoyl peroxide, and 28 parts of barium sulfate as the powder part; 98.1 parts of methyl methacrylate (containing 100ppm of hydroquinone), 1.9 parts of N, The N-dimethyl-p-toluidine was mixed well and used as the liquid part. Sterilize separately, take the powder part and the liquid part according to the ratio of 3:1, and store them in sterile cryopreservation tubes respectively.

Claims (6)

1. a kind of PMMA/SCTP composite micro-powder is characterized by having that core-shell structure, the core are methyl methacrylate and function The copolymer of monomer, crosslinking agent, the shell are tripolyphosphate calcium sodium.

2. a kind of PMMA/SCTP composite micro-powder as described in claim 1, be characterized in that preparation method the following steps are included:

(1) compound emulsifying agent is prepared, mix monomer, while the persulfate aqueous solution that compound concentration is 0.1%~10% are prepared；

The compound emulsifying agent includes lauryl sodium sulfate, dodecyl sodium sulfate, neopelex, succinic acid two Different monooctyl ester base sodium sulfonate, OP series emulsifier, Tween series emulsifier, Span series emulsifier, polyvinyl alcohol, carboxymethyl are fine Tie up one of element or any combination；

The mix monomer includes methyl methacrylate, function monomer and crosslinking agent, wherein methyl methacrylate, function list Body, crosslinking agent weight ratio be 1: 0.05~0.2: 0.001~0.1；

The function monomer is hydroxymethyl acrylate, hydroxy ethyl methacrylate, hydroxypropyl acrylate, hydroxyl butylacrylic acid Ester, hydroxymethyl methacrylate, hydroxyethyl meth acrylate, hydroxypropyl methacrylate, hydroxyl butyl methyl acrylic acid Ester, one of or any combination；

The crosslinking agent is ethyleneglycol dimethyacrylate, methacrylate diglycol ester, methacrylate One of Triethylene Glycol, bisphenol-A-glycidyl Methacrylate；

(2) 100 parts of deionized waters, 0.5 part~10 parts compound emulsifying agents, 6 parts~30 parts mixing lists are sequentially added into reaction kettle Body, while heating up and emulsifying, nitrogen filled protection；After being warming up to 80 DEG C, 0.1 part~1 part persulfate aqueous solution, reaction is added After 15min~60min, 20 parts~90 parts mix monomers at the uniform velocity are added dropwise simultaneously in 2h~3h and 0.1 part~2 parts potassium peroxydisulfates are molten Liquid；After dripping, continue insulation reaction 2h~3h；It is cooled to room temperature, is repeatedly centrifugated, deionized water flush cycle, Obtain methylmethacrylate copolymer microballoon；

(3) at room temperature, it is micro- that 100 parts of deionized waters, 1 part~20 parts methylmethacrylate copolymers are sequentially added into reaction kettle Ball, 0.2 part~4 parts templates, stirring is to dissolving, with sodium hydroxide tune pH value to 7.5~8.5；Calcium chloride water is added, stirs After mixing 15min~45min, it is 2: 1 addition tripolyphosphate sodium water solutions according to the molar ratio of calcium constituent and sodium element, reacts 0.3h ~2h, is aged 1h~2h, filtering, and ethanol washing is lyophilized, obtains PMMA/SCTP composite micro-powder；

The template is tyrosine, glycine, aspartic acid, glutamic acid, 6-aminocaprolc acid, maltodextrin, ethylenediamine tetraacetic One of acetic acid, disodium ethylene diamine tetraacetate, tetrasodium ethylenediamine tetraacetate.

3. a kind of PMMA/SCTP composite micro-powder as claimed in claim 1 or 2, is characterized in that methylmethacrylate copolymer The diameter of microballoon is between 0.02 μm~3 μm.

4. a kind of PMMA/SCTP composite micro-powder as claimed in claim 1 or 2, be characterized in that partial size 0.02 μm~200 μm it Between.

5. a kind of compound bone cement, is characterized in that being made of powder section and liquid portion, the powder section by 65 parts~ 75 parts of a kind of PMMA/SCTP composite micro-powder, 0.1 part~3 parts initiators and 24 parts~32 parts sulphur as described in Claims 1 to 4 Sour barium be uniformly mixed forms, the liquid portion by 90 parts~99.5 parts methyl methacrylates, 0.5 part~10 parts promotors and 60ppm~200ppm hydroquinone is uniformly mixed and forms；

The initiator is one of benzoyl peroxide, dilauroyl peroxide；

The promotor is N, N- dimethyl-p-toluidine, n,N-Dimethylaniline, N- methyl-N- (2- ethoxy)-p- first One of aniline.

6. a kind of compound bone cement as claimed in claim 5 is characterized in that the powder section and the liquid portion pass through Be individually enclosed in sterile chamber after aseptic process, using it is preceding according to the weight ratio 1.5~4: 1 of powder section and liquid portion into Row mixing.