CN109010909A - The compound erythromycin bone cement of polymethyl methacrylate is used to prevent and treat the application of Periprosthetic bone dissolution and inflammatory reaction - Google Patents

The compound erythromycin bone cement of polymethyl methacrylate is used to prevent and treat the application of Periprosthetic bone dissolution and inflammatory reaction Download PDF

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Publication number
CN109010909A
CN109010909A CN201811029778.XA CN201811029778A CN109010909A CN 109010909 A CN109010909 A CN 109010909A CN 201811029778 A CN201811029778 A CN 201811029778A CN 109010909 A CN109010909 A CN 109010909A
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erythromycin
bone
bone cement
polymethyl methacrylate
powder
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朱芳兵
王建岳
侯桥
章英良
曾林如
张治金
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HANGZHOU CITY XIAOSHAN DISTRICT TRADITIONAL CHINESE MEDICAL HOSPITAL
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HANGZHOU CITY XIAOSHAN DISTRICT TRADITIONAL CHINESE MEDICAL HOSPITAL
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/16Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406Antibiotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/24Materials or treatment for tissue regeneration for joint reconstruction

Abstract

The invention belongs to technical field of composite materials, and in particular to the compound erythromycin bone cement of polymethyl methacrylate is used to prepare the application in the drug of prevention and treatment Periprosthetic bone dissolution.The invention discloses the applications that the compound erythromycin bone cement of polymethyl methacrylate is used to prevent and treat Periprosthetic bone dissolution and inflammatory reaction, the compound erythromycin bone cement of polymethyl methacrylate has the significant dissolution of Periprosthetic bone and inflammatory reaction for inhibiting titanium particle to mediate, improve prosthese-bone interface bone density and bone amount score, prosthese-bone interface shear strength and stability are improved, the prevention and treatment of aseptic loosening of prosthesis is expected to be used for.

Description

The compound erythromycin bone cement of polymethyl methacrylate is molten for preventing and treating Periprosthetic bone The application of solution and inflammatory reaction
Technical field
The invention belongs to technical field of composite materials, and in particular to the compound erythromycin bone cement of polymethyl methacrylate is used Application in the drug of preparation prevention and treatment Periprosthetic bone dissolution and inflammatory reaction.
Background technique
Function patient is lost because of joint caused by degenerated and inflammatory arthritis there are about 1,500,000 every year and is manually closed in the whole world Save displacement technique.Treatment means of the artificial joint replacement as joint whole Terminal Disease and femoral neck fracture in elders, significantly improve The quality of life of patient.But with the extension of joint prosthesis service life, overhauls patient because a variety of causes need to go and gradually increase It is more.It needs to carry out joint prosthesis overhaul technology in 15 years after first artificial joint replacement there are about 10% patient.Some big Medical center, revision procedure case load have reached 20% or so of same period total hip arthroplasty, as China's medical treatment is defended The patient of the development for industry of making trouble, row artificial joint replacement is also more and more.Prosthese aseptic loosening has certain disease incidence, will That a serious health problem must be become, and influences whether more and more patients.Since the curative effect of overhaul technology is lower than just Secondary operation, operation wound is big, expensive, brings huge body and mind pain and economic pressures to patient.Therefore there is an urgent need to grind The newtype drug and material for studying carefully treatment prosthese aseptic loosening, joint prosthesis aseptic is prevented and treated by non-surgical way This late complication is loosened, there is important researching value and potential applicability in clinical practice.
The mechanism of aseptic loosening of prosthesis is complicated, is not fully understood so far.Majority scholar thinks nothing at present The main pathogenic that bacterium property loosens is the Cytobiology and molecular biology reaction of a series of complex as caused by wear particle, abrasion Particle acts on Ju Shi Xi Bao ﹑ Po Gu Xi Bao ﹑ Cheng Gu Xi Bao ﹑ fibroblast and lymphocyte in peri-prosthetic tissues, and one Aspect causes osteoclast activity to enhance, and the dissolution of Periprosthetic bone increases;The decline of still further aspect osteoblast activity, ostosis It reduces, local bone metabolic balance destroys, and aggravates prosthetic loosening process.Meanwhile wear particle induces above-mentioned cell secretion a series of Inflammatory factor, growth factor and chemotactic factor (CF) are further exacerbated by Periprosthetic inflammatory reaction.And the Nuclear factor kappa B receptor activation factor Ligand (the RANKL)/various signal paths of osteoprotegerin (OPG) system and downstream such as Nuclear factor kappa B(NF- κ B) and mitogen work Changing protein kinase, (MAPK) ﹑ Yangization Ying Ji ﹑ Nei matter net Ying Ji ﹑ Xi born of the same parents' Diao Wang ﹑ autophagy etc. both participates in regulation wear particle and mediates bone Course of dissolution.The cell biology and molecular biology depth that bone dissolution loosens reaction are being induced to the postoperative wear particle of joint prosthesis On the basis of entering research, many scholars have carried out many effort and trial to intervene this process.
Erythromycin is macrolide antibiotics, is applied to treat various infectious diseases for a long time.Recent numerous studies It was found that erythromycin can treat certain chronic inflammatory diseases not against its antibacterial functions, such as diffusivity capillary bronchitis, asthma, Chronic nasosinusitis, nasal polyp etc. analyze its mechanism, may inhibit IL-1 β, IL-6, the table of the cell factors such as TNF-α with erythromycin Up to related, and these factors have important role for the generation, differentiation and maturation of osteoclast, prompt erythromycin that can inhibit The inflammatory reaction that wear particle induces has therapeutic value for the bone dissolution that wear particle induces, it is expected to as a kind of potential Medical treatment aseptic loosening of prosthesis.Research confirms that erythromycin can inhibit ultra-high molecular weight polyethylene wear particle to lure The inflammatory bone of hair dissolves, it is suppressed that inflammatory factor such as IL-1 β, IL-6, TNF-α, RANKL and Proteinase K expression promote OPG table It reaches, inhibits osteoclast activity, promote osteoblast activity, inhibit Periprosthetic bone course of dissolution, improve Periprosthetic bone amount For preventing and treating joint prosthesis aseptic pine.Clinical safety, validity and its distinctive molecular target of erythromycin have it can A kind of drug for treating prosthetic loosening can be become.
Summary of the invention
In order to avoid the generation and raising Periprosthetic part erythromycin drug effect of erythromycin system application systemic adverse reactions Concentration, it is an object of the present invention to provide the compound erythromycin bone cements of polymethyl methacrylate to be used to prepare prevention and treatment prosthese week The application in the drug of bone dissolution and inflammatory reaction is enclosed, it is compound that a second object of the present invention is to provide polymethyl methacrylates Erythromycin bone cement is used to prepare the application in the drug of prevention and treatment aseptic loosening of prosthesis, and third object of the present invention is The compound erythromycin bone cement of polymethyl methacrylate is provided, for preventing and treating aseptic loosening of prosthesis.Of the invention the 4th A purpose is to provide the preparation method of the compound erythromycin bone cement of above-mentioned polymethyl methacrylate.
In order to realize first above-mentioned purpose, present invention employs technical solutions below:
The compound erythromycin bone cement of polymethyl methacrylate is used to prepare the medicine of prevention and treatment Periprosthetic bone dissolution and inflammatory reaction Application in object.
Preferably, evenly dispersed in PMMA bone cement have erythromycin powder, erythromycin powder contains Amount is 0.2% ~ 2%.Further preferably, the content of erythromycin powder is 0.5 ~ 1%.
In order to realize second above-mentioned purpose, present invention employs technical solutions below:
The compound erythromycin bone cement of polymethyl methacrylate is used to prepare in the drug of prevention and treatment aseptic loosening of prosthesis Using.
Preferably, evenly dispersed in PMMA bone cement have erythromycin powder, erythromycin powder contains Amount is 0.2% ~ 2%.The content of erythromycin powder is 0.5 ~ 1%.
In order to realize above-mentioned third purpose, present invention employs technical solutions below:
A kind of compound erythromycin bone cement of polymethyl methacrylate, which includes PMMA bone cement, Evenly dispersed in PMMA bone cement to have erythromycin powder, the content of erythromycin powder is 0.2% ~ 2%.
Preferably, the content of erythromycin powder is 0.5 ~ 1%.
In order to realize the 4th above-mentioned purpose, present invention employs technical solutions below:
A method of the compound erythromycin bone cement of polymethyl methacrylate of the prevention and treatment Periprosthetic bone dissolution is prepared, This method includes the following steps: in PMMA bone cement uniformly to mix erythromycin powder, and rear be added is gathered Methyl methacrylate bone cement liquid monomer is sufficiently stirred rear injected plastic mold, takes out after solidification.
Preferably, the quality of PMMA bone cement and PMMA bone cement liquid monomer Than for 1:1 ~ 3:1.
The bioavilability of erythromycin can be improved by load erythromycin bone cement slow-released system by the present invention, reduce system The systemic adverse reactions of administration.Erythromycin stable in physicochemical property, thermal stability is high, and the characteristics such as soluble make it as most of load Antibiotic is equally resistant to the high temperature generated in bone cement polymerization process and is easy to discharge, and is playing local antibacterial effect simultaneously, Aseptic loosening of prosthesis can be effectively prevented.The bioactive materials polymethyl methacrylate that the present invention designs is compound red mould The advantages that plain bone cement has drug dose small, and adverse reaction is few, and local concentration is high, long action time, passes through non-surgical way It prevents and treats this late complication of aseptic loosening of prosthesis, there is important potential applicability in clinical practice.Through animal reality Verifying is real, and Novel Bioactive Material of the present invention has the significant Periprosthetic bone dissolution for inhibiting titanium particle to mediate and inflammation anti- It answers, improves prosthese-bone interface bone density and bone amount score, improve prosthese-bone interface shear strength and stability, prompt poly- first The compound erythromycin bone cement of base methyl acrylate effectively inhibits the induction Periprosthetic bone dissolution of titanium particle, is expected to be used for joint prosthesis The prevention and treatment of aseptic loosening.
Detailed description of the invention
Fig. 1 is present invention figure compared with positive controls femoral prosthesis surrounding bone density.
Fig. 2 is that bone cement-femur interface shearing-resistance shearing stress compares figure.
Fig. 3 is postoperative 8 weeks Periprosthetic limitans structure observation (HE dyeing × 100) figure.
Fig. 4 is postoperative 8 weeks bone amount score quantitative analysis figure.
Specific embodiment
1. experimental design and grouping
Adult male New Zealand rabbit 42,2.19 ± 0.17 kg of weight.Preoperative adaptive feeding one week, it is random according to weight It is divided into 6 groups: negative control group (A, n=7): without the intervention of titanium particle and erythromycin drug therapy;Positive controls (B, n= 7): giving the intervention of titanium particle but without erythromycin drug therapy;Local treatment group: titanium particle intervention, while load mass point are given Number be respectively 0.1 wt%(C, n=7), 0.5 wt%(D, n=7), 1.0 wt%(E, n=7) erythromycin as part Administration group;Systematic treating group (F, n=7): titanium particle intervention, while erythromycin suspension (1.0 mg/kg/w) work is subcutaneously injected For the group that is administered systemically.Rabbit femoral distal end implantation PMMA bone cement stick simulating bone-cement type joint replacement, art Middle femoral bone cavitas medullaris and postoperative 2 ﹑ 4 ﹑, 6 weeks two knee joint cavities inject titanium particle building aseptic loosening model respectively.
Material and instrument
Acrylic acid bone cement is commercially available CMW Endurance bone cement, (Depuy Int., Leeds, UK).Poly- methyl-prop E pioic acid methyl ester (PMMA) ingredient, interior packaging includes that 40 g PMMA powder one wrap, one 20 mL of MMA liquid monomer.
Erythromycin standard items, Chinese biological pharmaceutical biological product examine and determine institute, and (PBS contains NaCl to phosphate buffer solution 8.00 g、Na2HPO4 2.38 g、KH2PO40.19 g, pH 7.4).
Femur-bone cement interfacial shearing stress test material experimental machine, aerospace institute of the Zhejiang University mechanics of materials are real It tests room and (Zwick/Roell Z2.5, Zwick GmbH & Co., Ulm, Germany) is provided.
Titanium particle: the offer of AlfaAesar (Tianjin) Chemical Co., Ltd. (Catalog:00681, Lot:H08N21, Johnson Matthey Co., Ward Hill, MA, USA).
New zealand rabbit is provided by academy of agricultural sciences of Zhejiang Province Experimental Animal Center.
Dual-energy X-rays absorptionmetry, Shaoyifu Hospital Attached to Zhejiang Univ. Medical College's offer (DEXA, Lunar DXP-IQ, Lunar Corporation, Madison, WI, USA; Software DPX-IQ X-Ray Bone Densitometer With SmartScan TM Version 4.7e).
Olympus optical microscopy, Zhejiang University's orthopaedics laboratory provide (Olympus BX51, Olympus Optical Co. Ltd., Tokyo, Japan).
Bone amount score quantified system analysis: 6.0 image analysis system of Image-pro plus (Media Cybernetics Inc., Silver Spring, MA, USA)
Titanium particle endotoxin detection kit: Xiamen reagents factory (Chromogenic End-point TAL with a Diazo coupling kit, Xiamen Houshiji Co., Fujian, China).
3% yellow Jackets, 1% sodium hyaluronate solution Shanghai Sheng Gong bio-engineering corporation provide.EDTA decalcifying Fluid, Beijing Co., Ltd of Zhong Shan Golden Bridge provides.
Method
The preparation of 3.1 erythromycin bone cement materials
The erythromycin powder of 40 mg, 201 mg and 404 mg are uniformly mixed in 40 g of PMMA respectively, 18.88 are added afterwards G bone cement liquid monomer is sufficiently stirred rear injected plastic mold (3.2 mm of internal diameter), takes out after solidifying 20 min, as quality Score is respectively 0.1 wt%, and post-processing examination is fully cured to bone cement in the erythromycin bone cement test specimen of 0.5 wt%, 1.0 wt% Part is at uniform cylindrical body (15 mm of length;3.2 mm of diameter), visually the examination that internal void is greater than 1 mm is rejected with x ray photograph Part.All preoperative 1 h of oxirane disinfection of test specimen are placed in sterile sealing polybag, and 4 DEG C of refrigerators save.
The preparation of 3.2 titanium particle suspensions and detection
Pure titanium particle is confirmed through Electronic Speculum: 2.9 μm of average diameter, 99.5% less than 45 μm, and 93% less than 20 μm.By pure titanium particle It is placed in 70% alcohol and vibrates bathing 24 hours, add absolute alcohol soaked overnight afterwards, after the cleaning three times of sterile phosphate buffer solution It is dry, particle addition carrier solution (1% sodium hyaluronate solution: PBS solution=1:3) is made into 1.2 × 108/ mL suspension, through height 4 °C of refrigerators after moise-heat sterilization are pressed to save.It separately takes 2 mL particle suspensions to detect particle endotoxin according to reagents detection kit to live Property, it was demonstrated that activity of endotoxin is less than 0.25 EU/mL.
The operation of 3.3 aseptic loosening model constructions
After the anesthesia of 3% yellow Jackets (1 mL/kg) rabbit auricular vein, knee joint shaving is sterilized, and inner incision is layered before knee joint Cut skin, subcutaneous tissue, deep fascia and joint capsule, outer lateral dislocation before kneecap, buckling knee joint exposure femur lower edge, low speed electricity It bores parallel femur long axis direction and bores an osseous tunnel (3.2 mm of diameter, 15 mm of depth) at femoral intercondylar ridge.5 mL freeze physiology The hemostasis of salt water repeated flushing tunnel, A group inject Sodium Hyaluronate and 0.3 mL of PBS mixed carrier solution, remaining group of injection equivalent titanium Particle suspension (about titaniferous particle 3.6 × 107).Press-fit is placed in acrylic acid bone cement test specimen afterwards.Reset kneecap after No. 4 lines by Layer suture.Preoperative 30 min and postoperative 400,000 unit of intramuscular injection penicillin, it is postoperative to give in 150 mL intravenous drip prosthetics of sugar-salt-water Body fluid is lost.Animal house, sub-cage rearing are sent back to after anesthesia is awake.Penicillin prevention infection 7 days, intramuscular injection 2 times a day, every time 400,000 Unit.Postoperative 2,4, the 6 weeks two sides knee joint cavities injection Sodium Hyaluronate of A group and 0.6 mL of PBS mixed carrier solution, remaining group corresponding Time injects equivalent titanium particle suspension (about titaniferous particle 7.2 × 107).Postoperative one week subcutaneous injection erythromycin suspension 2 of F group The suspension of mL(physiological saline and tablet), 1.0 mg/kg of dosage, after once a week.
The preparation of 3.4 samples and preservation
The titanium particle on postoperative 8 weeks all animals of excessive anaesthesia execution, dissection two sides femur, Ti Jing surrounding soft tissue and surface is residual It is remaining.All samples row Mo-target-X-ray photography immediately observes prosthese position.Left femur physiological saline gauze package is placed on -20 DEG C Refrigerator saves, and plans to implement Periprosthetic bone density and interfacial shearing stress test;Right side femur is placed in 10% neutral formalin solution Middle fixation, row bone tissue morphological observation and bone amount score quantitative analysis.
The test of 3.5 Periprosthetic bone densities
Femur is faced upward and is placed on poly (methyl methacrylate) plate, Dual-energy X-rays absorptionmetry measures each group Periprosthetic bone density.Scanning speed 10 Mm/min, the step pitch mm of 1.0 mm × 1.0, accuracy and accuracy are 1.0%.The toy carried using the system is interested Software (DPX-4.7e) carries out calibration analysis, measures Periprosthetic bone density value.
The test of 3.6 femurs-bone cement interfacial shearing stress
Row interfacial shearing stress is analyzed after bone density test.Fixture resected femur sample is customized, adjustment femur y direction makes bone Cement prosthese is consistent with loading direction, and axial compression pressure is loaded after zeroing, preloads 2 N, 5 mm/min of loading speed, load From distal femur near end of thighbone, when test, physiological saline pours repeatedly in direction keeps femur wet.It is bent to record pressure-displacement Line, stops load when until interfacial displacement is up to 5 mm, record maximum load value, that is, interface maximum shear stress F at this timemax(N).
3.7 bone tissue morphological observations and analysis
10% neutral formalin of femur specimen fixes 3 d, and serial dehydration of alcohol after 4 d of decalcification takes out row paraffin after bone cement test specimen Embedding, the vertical femur long axis serial section of LeicaRM2135 slicer (100 μm of slice spacings), slice are respectively positioned on prosthese head With remote 2-4 mm, 3.5 μm of thickness, each femur specimen is sliced 5, and rear row hematoxylin-eosin (HE) is dyed, Olympus light Learn microscopically observation Periprosthetic limitans and bone trabecula morphosis.
It retains picture and carries out the quantitative analysis of bone amount score.6.0 image analysis software of Image-pro plus chooses figure respectively RED sector (bone trabecula) and elemental area size is calculated in piece, it is rear to calculate the total elemental area size of picture, it is calculated according to formula Bone amount score: bone trabecula elemental area/slice elemental area × 100%.
3.8 statistical analysis
The measurement data of normal distribution indicates that partial velocities are indicated with M ± Q with x ± s.A group and B group row are set in groups Count lower independent sampletIt examines.After normal distribution and homogeneity test of variance, medication therapy groups (C, D, E, F) and positive controls (B) row one-way analysis of variance and two-by-two between LSD-tIt examines.p < 0.05 is statistically significant for difference.
As a result
1, femoral prosthesis surrounding bone density as shown in Figure 1 compares (unit: g/cm2): positive controls Periprosthetic bone density Significantly lower than negative control group, titanium particle is prompted to promote osteoclast activity, inhibits osteoblast activity, lead to Periprosthetic bone Density decline prompts the success of aseptic loosening of prosthesis model construction;The mass fraction erythromycin of Combined Loading 0.5% and 1% Polymethylacrylic acid bone cement group bone density is apparently higher than positive controls, reaches and the same control efficiency that is administered systemically.# with Positive controls compare, p < 0.05, Group Design independent samples t test;* compared with positive controls, p < 0.05, LSD- T is examined.
2, bone cement shown in Fig. 2-femur interface shearing-resistance shearing stress compares (unit: N).Positive controls prosthese-bone circle Face shear strength is significantly lower than negative control group, prompts titanium particle to mediate Periprosthetic bone resorption and bone dissolution, reduces prosthese Fixing intensity prompts the success of aseptic loosening of prosthesis model construction;The mass fraction erythromycin of Combined Loading 0.5% and 1% Polymethylacrylic acid bone cement group shear strength is apparently higher than positive controls, reaches and the same prevention and treatment that is administered systemically is imitated Fruit.# is compared with positive controls, p < 0.05, Group Design independent samples t test;* compared with positive controls, p < 0.05, LSD-t examines.
3, postoperative 8 weeks Periprosthetic limitans structure observation as shown in Figure 3 (HE dyeing × 100) A: negative control group, Periprosthetic bone trabecula form is complete, without obvious bone resorption sign;B: positive controls, it is seen that apparent bone resorption, limitans are bright Aobvious to be thicker than negative control group, visible titanium distribution of particles (shown in arrow), bone trabecula continuity are interrupted therebetween, and centre is by fibr tissue Substitution;C and E:0.1% and 1.0% local load's group, limitans is thin compared with positive controls, but still visible fibrous tissue distribution and bone It absorbs;D and F:0.5% local load group and the group that is administered systemically, for Periprosthetic without obvious limitans tissue, bone trabecula form is complete.It mentions Show the Periprosthetic inflammatory reaction for inhibiting titanium particle to mediate after local erythromycin load.
4, postoperative 8 weeks bone amount score quantitative analysis as shown in Figure 4.Positive controls Periprosthetic bone amount score is obviously low In negative control group, titanium particle is prompted to promote osteoclast activity, inhibits osteoblast activity, Periprosthetic bone amount is caused to be lost It loses, prompts the success of aseptic loosening of prosthesis model construction;The poly- methyl of the mass fraction erythromycin of Combined Loading 0.5% and 1% Acrylic acid bone cement group bone amount score is apparently higher than positive controls, reaches and the same control efficiency that is administered systemically.# and the positive Control group compares, p < 0.05, Group Design independent samples t test;* compared with positive controls, p < 0.05, LSD-t inspection It tests.

Claims (10)

1. the compound erythromycin bone cement of polymethyl methacrylate is used to prepare the dissolution of prevention and treatment Periprosthetic bone and inflammatory reaction Application in drug.
2. application according to claim 1, which is characterized in that in PMMA bone cement it is evenly dispersed have it is red Mycin powder, the content of erythromycin powder are 0.2% ~ 2%.
3. application according to claim 2, which is characterized in that the content of erythromycin powder is 0.5 ~ 1%.
4. the compound erythromycin bone cement of polymethyl methacrylate is used to prepare in the drug of prevention and treatment aseptic loosening of prosthesis Application.
5. application according to claim 4, which is characterized in that in PMMA bone cement it is evenly dispersed have it is red Mycin powder, the content of erythromycin powder are 0.2% ~ 2%.
6. application according to claim 5, which is characterized in that the content of erythromycin powder is 0.5 ~ 1%.
7. a kind of compound erythromycin bone cement of polymethyl methacrylate, the bone cement include polymethyl methacrylate bone water Mud, which is characterized in that evenly dispersed in PMMA bone cement to have erythromycin powder, the content of erythromycin powder is 0.2%~2%。
8. the compound erythromycin bone cement of a kind of polymethyl methacrylate according to claim 7, which is characterized in that red mould The content of plain powder is 0.5 ~ 1%.
9. a kind of method for preparing the compound erythromycin bone cement of polymethyl methacrylate described in claim 7 or 8, feature It is, this method includes the following steps: in PMMA bone cement uniformly to mix erythromycin powder, rear to add Enter PMMA bone cement liquid monomer, rear injected plastic mold is sufficiently stirred, is taken out after solidification.
10. according to the method described in claim 9, it is characterized in that, PMMA bone cement and polymethyl The mass ratio of sour methacrylate bone cement liquid monomer is 1:1 ~ 3:1.
CN201811029778.XA 2018-09-05 2018-09-05 The compound erythromycin bone cement of polymethyl methacrylate is used to prevent and treat the application of Periprosthetic bone dissolution and inflammatory reaction Pending CN109010909A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113367787A (en) * 2021-06-11 2021-09-10 苏州奥芮济医疗科技有限公司 Preparation method of tumor bone incisal margin filler for preventing prosthesis loosening and postoperative recurrence of tumor

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000047214A1 (en) * 1999-02-09 2000-08-17 Sloan-Kettering Institute For Cancer Research Anti-resorptive bone cements and allogeneic, autografic, and xenografic bone grafts
CN101511396A (en) * 2006-05-02 2009-08-19 凯丰有限责任公司 Bone cement compositions comprising an indicator agent and related methods thereof
US20160158405A1 (en) * 2013-07-10 2016-06-09 Stephen Denyer Liposomal drug delivery system for bone cements
CN105833258A (en) * 2016-06-16 2016-08-10 扬州市第人民医院 Application of ulinastatin to preparation of medicine for preventing and treating granulosis
CN107041968A (en) * 2016-12-13 2017-08-15 杭州市萧山区中医院 One kind prepares ZrO2The HA dip-coating slurries of Bone Defect Repari bioceramic scaffold material

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000047214A1 (en) * 1999-02-09 2000-08-17 Sloan-Kettering Institute For Cancer Research Anti-resorptive bone cements and allogeneic, autografic, and xenografic bone grafts
CN101511396A (en) * 2006-05-02 2009-08-19 凯丰有限责任公司 Bone cement compositions comprising an indicator agent and related methods thereof
US20160158405A1 (en) * 2013-07-10 2016-06-09 Stephen Denyer Liposomal drug delivery system for bone cements
CN105833258A (en) * 2016-06-16 2016-08-10 扬州市第人民医院 Application of ulinastatin to preparation of medicine for preventing and treating granulosis
CN107041968A (en) * 2016-12-13 2017-08-15 杭州市萧山区中医院 One kind prepares ZrO2The HA dip-coating slurries of Bone Defect Repari bioceramic scaffold material

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
W. REN等: "Underappreciated benefits of erythromycin in the management ofperiprosthetic inflammation and osteolysis", 《BONE》 *
张希昌: "《骨水泥》", 31 October 1997, 中国标准出版社 *
韩俊柱等: "辛伐他汀和红霉素对人工关节松动模型小鼠的干预效果", 《新乡医学院学报》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113367787A (en) * 2021-06-11 2021-09-10 苏州奥芮济医疗科技有限公司 Preparation method of tumor bone incisal margin filler for preventing prosthesis loosening and postoperative recurrence of tumor

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