CN102721796A - Experimental device for simulating local drug release behavior of medicine and application thereof - Google Patents
Experimental device for simulating local drug release behavior of medicine and application thereof Download PDFInfo
- Publication number
- CN102721796A CN102721796A CN2012102236471A CN201210223647A CN102721796A CN 102721796 A CN102721796 A CN 102721796A CN 2012102236471 A CN2012102236471 A CN 2012102236471A CN 201210223647 A CN201210223647 A CN 201210223647A CN 102721796 A CN102721796 A CN 102721796A
- Authority
- CN
- China
- Prior art keywords
- drug
- material storehouse
- storehouse
- medicine
- material bin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses an experimental device for simulating a local drug release behavior of a medicine and an application thereof. The device comprises a solution charging chamber, a flow rate control valve, an experimental material bin and a receiving chamber, wherein the solution charging chamber, the flow rate control valve, the experimental material bin and the receiving chamber are connected sequentially through conduits; the experimental material bin comprises a constant temperature bin, an upper material bin and a lower material bin, the upper material bin and the lower material bin are both of hollow structures, the upper material bin is connected with the flow rate control valve through the conduit, the lower material bin is connected with the receiving chamber through the conduit, the upper material bin and the lower material bin can be connected into a whole through bolts and placed in the constant temperature bin. The experimental device for simulating the local drug release behavior of a medicine can be used for studying an in vitro local drug release behavior of a medicine-loaded implant material, understanding local drug concentrations at different times and acquiring the drug release speed and accumulated release amount, so that experimental data are provided to clinical application.
Description
Technical field
The invention belongs to drug world, relate in particular to the experimental provision and the application thereof of a kind of aids drug local delivery of drug behavior.
Background technology
The development of surgery operating technology and new medical embedded material is used widely the embedded material of carrying medicament (especially microbiotic).Like the application of bone cement carried with antibiotics in multiple surgery, bone surgery, brought into play definite curative effect at aspects such as treatment fracture, osteomyelitis, joint replacements.Bone cement commonly used has 4 big types: 1. do not have the bone cement of bone conductibility, like polymethylmethacrylate (PMMA).2. the bone cement that has bone conductibility is like hydroxyapatite, pottery etc.3. biodegradable bone cement is like calcium phosphate, calcium sulfate bone cement.4. other, like strontium hydroxylapatite, natural coral bone substitute, composite bone cement, TGF etc.
The microbiotic of embedded material load mainly contains gentamicin, TOB and vancomycin etc.Gentamicin is a kind of aminoglycoside antibiotics, is mainly used in the treatment bacterial infection, the especially infection that causes of Gram-negative bacteria.TOB is a kind of aminoglycoside antibiotics, molecular formula: C
18H
37N
5O
9TOB can be bound up on the coupled position of 30S and 50S, hinders the formation of 70S compound, makes mRNA can not translate into protein, causes cell death.Mainly to gram-negative bacteria, effective like Pseudomonas aeruginosa, Escherichia coli, klebsiella bacillus, Enterobacter, proteus, citrobacter.Clinically be mainly used in the severe infections that sensitive bacterial causes, like gram-negative bacteria infection of burn, septicemia, infection in respiratory system, urinary system infection contamination, gall-bladder infection of biliary tract and the soft tissue severe infections etc. that cause such as Pseudomonas aeruginosa, Escherichia coli and pneumobacillus particularly.Vancomycin by a kind of streptomycete produce, baroque glycopeptide antibiotics, its molecular formula is C
66H
74C
1N
9O
24The system that is mainly used in due to staphylococcus (comprising penicillin resistant and anti-celbenin strain), the clostridium difficile etc. infects and enteric infection, like endocarditis, septicemia, pseudomembranous enteritis etc.Vancomycin can suppress the synthetic of bacteria cell wall, and is strong to effects such as staphylococcus aureus, streptococcus pyogenes, streptococcus pneumonias.
All there are the ear renal toxicity in vancomycin and gentamicin, and severe renal infringement possibly take place when overdose or renal insufficiency, show as blood urine, urine amount too much or reduce, even uremia takes place.Also can cause tinnitus, dysacousis, even cause irreversible deafness.The common bad reaction of the TOB of topical application is local toxic and side effect and allergic reaction.If but TOB and other aminoglycoside antibiotics whole body drug combinations just should note monitoring drug concentration total in the serum.
At present clinical practice load microbiotic embedded material carries out various operations, and used microbiotic dosage is main with the experience medication, medicine and embedded material combine and drug release characteristics remains further to be studied.In order to ensure data for clinical drug use, and optimize microbiotic dosage and usage, promote that microbiotic rationally uses, be necessary to carry out antibiotic drug release process in the carried with antibiotics embedded material.Through document retrieval, the research of minority bone cement physicochemical property and vitro drug release behavior, adopt the elution characteristic of water bath with thermostatic control lixiviate experimental study medicine carrying material more, drug environment and the process existence in vivo of research method and medicine carrying material is than big-difference.
The research device that is used to study the drug behavior also has transdermal test in vitro absorption plant (Franz pond), is mainly used in the drug transdermal dispersal behavior research of transdermal drug delivery system.Oral drugs dissolution rate appearance is mainly used in aids drug at gastral dissolution time and dissolution rate.Micro-dialysis device belongs to trace sampling apparatus, is mainly used in the drug behavioral study in the animal body.Above-mentioned experimental provision can't satisfy the needs of medicine local delivery of drug behavioral study.Through retrieval, do not see the bibliographical information of external medicine drug release behavior research.
Summary of the invention
The objective of the invention is deficiency, a kind of experimental provision that is used for topical remedy's release behavior research is provided, carry out the drug release behavior of embedded material Chinese traditional medicine,, promote safety, the rational use of medicines for clinical practice provides experimental basis to prior art.
The objective of the invention is to realize: the experimental provision of aids drug local delivery of drug of the present invention behavior through following technical scheme; It comprises: add liquid chamber, flow control valve, experiment material storehouse and receiving chamber, add liquid chamber, flow control valve, experiment material storehouse and be connected through conduit successively with receiving chamber.
Further; The experiment material storehouse comprises thermostatical storehouse, top, material storehouse and bottom, material storehouse; Top, material storehouse and bottom, material storehouse are hollow structure, and top, material storehouse links to each other with flow control valve through conduit, and bottom, material storehouse links to each other with receiving chamber through conduit; Top, material storehouse and bottom, material storehouse can link into an integrated entity through bolt, and place in the thermostatical storehouse.
The application of the experimental provision of a kind of above-mentioned aids drug local delivery of drug behavior; Specifically; The experimental provision of aids drug local delivery of drug of the present invention behavior can be used for studying the external topical remedy release behavior of medicine carrying embedded material; Understand the local drug concentration of different time, obtain drug release rate and accumulative total burst size, for clinical practice provides experimental data.
The invention has the beneficial effects as follows:
1, design innovation property
Because at present a limited number of drug release feature research reports about embedded materials such as medicine carrying bone cements adopt the experiment of water bath with thermostatic control lixiviate or ultrasonic Extraction, the elution characteristic of research medicine carrying material more.Experimentation is static relatively process, exists than big-difference with dynamic drug release process in the body.The present invention is with the diacolation principle; Innovative design the experimental provision of local delivery of drug behavioral study; Adopt dynamic seepage flow mode, drug release process in the body of simulation medicine carrying embedded material, design innovation; Method advanced person is feasible, can apparatus and experimental program be provided for topical remedy's releasing research of medicine carrying embedded material.
2, methodological science is reasonable
Adopt experimental provision of the present invention, through the adjustment of different parameters, condition, like adjustment percolating fluid consumption, percolation flow velocity and experimental period etc., simulation different pharmaceutical, different embedded material are treated the process of different clinical indications.Design and adjustment to sampling time point can provide diversified experimental data, satisfy the needs of different experiments.
3, potential applicability in clinical practice and function well
The medicine carrying embedded material increases in Clinical Application day by day; Adopt experimental provision of the present invention; Can carry out systematic study for the drug behavior of various medicine carrying embedded materials; Be medicine carrying injectivity optimizing, the drug release feature research of embedded material, and the applied research in clinical treatment provides experimental provision and method.Potential applicability in clinical practice is good, can bring into play positive effect for clinical rational drug use.
Description of drawings
Fig. 1 is an experimental provision synoptic diagram of the present invention;
Fig. 2 is an experiment material chamber structure synoptic diagram of the present invention;
Fig. 3 is embodiment 1 medicine time-concentration and accumulative total releasing curve diagram;
Fig. 4 is embodiment 2 medicine time-concentration and accumulative total releasing curve diagram;
Fig. 5 is embodiment 3 medicine time-concentration and accumulative total releasing curve diagram;
Among the figure, add liquid chamber 1, flow control valve 2, experiment material storehouse 3, receiving chamber 4, thermostatical storehouse 5, top, material storehouse 6, bottom, material storehouse 7.
Embodiment
As shown in Figure 1, the experimental provision of aids drug local delivery of drug of the present invention behavior comprises: add liquid chamber 1, flow control valve 2, experiment material storehouse 3 and receiving chamber 4, add liquid chamber 1, flow control valve 2, experiment material storehouse 3 and receiving chamber 4 and be connected through conduit successively.
Concrete structure is following:
1, add liquid chamber: be used to deposit percolating fluid, like physiological saline, artificial organ liquid, and the tissue liquid etc. of drug not; Have following characteristic: be shaped as right cylinder or rectangular parallelepiped, on sealable filling opening is arranged, the percolating fluid outlet is arranged down.
2, flow control valve: be used to control the flow velocity of percolating fluid, the seepage flow liquid measure of simulation clinical case postoperative different times; Have following characteristic: adjustable flow velocity, minimum flow velocity control accuracy reach 5 μ L/min; There is percolating fluid to import and export up and down.
3, experiment material storehouse: be used to place the medicine carrying embedded material; Its structure is as shown in Figure 2; Comprise thermostatical storehouse 5, top, material storehouse 6 and bottom, material storehouse 7; Top, material storehouse 6 is hollow structure with bottom, material storehouse 7, and top, material storehouse 6 links to each other with flow control valve 2 through conduit, and bottom, material storehouse 7 links to each other with receiving chamber 4 through conduit; Top, material storehouse 6 can link into an integrated entity through bolt with bottom, material storehouse 7, and places in the thermostatical storehouse 5.
4, receiving chamber: be used to receive the pastille percolating fluid after seepage flow finishes,, calculate drug concentration, accumulative total burst size, the local delivery of drug behavioral trait of research medicine through measuring the medicament contg in the percolating fluid.
Each building block of the present invention, except that the liquid outlet of sealable filling opening that adds liquid chamber 1 and receiving chamber 4, all the other liquid entrances all adopt flexible pipe or joint to connect, with for convenience detach, cleaning.
Device of the present invention can be used for studying the external topical remedy release behavior of medicine carrying embedded material, understands the local drug concentration of different time, obtains drug release rate and accumulative total burst size, and for clinical practice provides experimental data, its step is following:
1, preparation percolating fluid
Do not use the clinical patient tissue fluid of waiting to study medicine with physiological saline, artificial organ liquid or collection, as percolating fluid, 4 ℃ of refrigerations are subsequent use.
2, preparation medicine carrying embedded material
3, with the medicine carrying embedded material bottom, material storehouse of packing into, with bolt top, material storehouse and bottom, material storehouse are coupled together, and place thermostatical storehouse, will add liquid chamber, flow control valve, experiment material storehouse and receiving chamber through conduit at last and be connected in turn.
4, get the percolating fluid of step 1, add certainly in the filling opening of liquid chamber and add; The ON cycle thermostatted water, water temperature is a human body temperature, keeps the temperature constant state in experiment material storehouse; According to the percolation flow velocity that the seepage flow needs are regulated flow control valve to needs, beginning seepage flow is regularly supplied the percolating fluid that adds in the liquid chamber in the flow event.
When 5, taking a sample, open the receiving chamber liquid outlet, collect the pastille percolating fluid, collect the back and seal outlet, continue seepage flow; The pastille percolating fluid supplies assay to use-10 ℃ of freezing preservations.
6, seepage flow finishes, and closes the circulation thermostatted water, stripping assembly; Get the medicine carrying embedded material, weigh, stored refrigerated is carried out medicine assay.
7, get the pastille percolating fluid of step 5, and the residual medicine carrying embedded material of step 6, carry out medicine assay.
8, data analysis: according to percolating fluid Chinese traditional medicine assay result, calculate drug concentration, curve when drawing medicine calculates drug release rate and accumulative total burst size.Finish the medicine assay result in the embedded material of back according to seepage flow, calculate residual dose.Through analysis, optimize the therapeutic scheme of medicine carrying embedded material to drug release behavior characteristic and residual dose.
Describe use of the present invention in detail according to embodiment below, it is more obvious that the object of the invention and effect will become.
1, preparation percolating fluid: get physiological saline, 1000mL adopts cryoscopic method to measure osmotic pressure altogether, and osmotic pressure is: 312mOsm/kg; Adopt acidometer to measure the pH value, the pH value is 7.0, opens rearmounted 4 ℃ of stored refrigerated, and is subsequent use.
2, preparation medicine carrying embedded material:
Get vancocin vial powder-injection (trade name Vancomycin) 4g, other takes by weighing calcium sulphate artificial bone (OSTEOSET, U.S. WRIGHT medical skill group) 3g, mixes, and stirs; Other takes by weighing Cemex XL, and (Italy) bone cement 3g mixes the vancomycin mixture of calcium sulfate with bone cement for Tecres SpA, Verona, fully stirs; Add thinning agent 5mL, fully stirring reaction; Potpourri is placed the ultrasonic Extraction appearance, and ultrasonic 3min is to get rid of bubble; Medicine carrying bone cement slurries are evenly injected the 1mL syringe of pulling out injection putter, and above-mentioned bone cement slurry can be filled 4 1mL syringes; Bubble is got rid of in vibration; Treat to remove syringe after bone cement solidifies, promptly obtain the about 6mm of diameter, cylindric medicine carrying embedded material 1-1,1-2,1-3 and the 1-4 of the about 8cm of length.Weigh, weight is respectively: 1-1,3.842g, 1-2,3.734g, 1-3,3.790g and 1-4,3.710g.Get 1-1 medicine carrying embedded material, carry out the vancomycin assay, the assay result is: contain vancomycin 0.253g in every 1g medicine carrying embedded material, the release behavior experiment of the outer topical remedy of all the other medicine carrying vegetable material donors.
3, get 1-3 medicine carrying embedded material in the step 2; The bottom, material storehouse of packing into; With bolt top, material storehouse and bottom, material storehouse are coupled together, and place thermostatical storehouse, will add liquid chamber, flow control valve, experiment material storehouse and receiving chamber through conduit at last and be connected in turn.
4, get the percolating fluid of step 1, add certainly in the filling opening of liquid chamber and add; Open the thermostatical storehouse outside the experiment material storehouse, water temperature is set to 37 ℃, and promptly human body temperature is kept the temperature constant state in experiment material storehouse; The adjusting percolation flow velocity is 0.2mL/min, beginning seepage flow.Percolation flow velocity adjustment program is: 1d, 0.2mL/min; 2d, 0.14mL/min; 3-5d, 0.02mL/min; 6d, 0.01mL/min; 7-10d, 0.008mL/min; 11-15d, 0.005mL/min.Above-mentioned percolation flow velocity according to clinical patients postoperative same day to wound healing till, during wound ooze out law formulation.Regularly supply the percolating fluid in the charger in the flow event, guarantee to add liquid chamber and have the seepage flow that enough percolating fluids can continue.
5, begin 12h, 1,2,3,4,5,6,7,8,9,10,11,12,13,14 and 15d respectively at seepage flow, open the receiving chamber liquid outlet, collect the pastille percolating fluid, collect back seal fluid outlet; The pastille percolating fluid of collecting, metered volume is: 12h-141mL, 1d-140mL, 2d-200mL, 3d-29mL, 4d-29mL, 5d-28mL, 6d-14mL, 7d-11mL, 8d-11mL, 9d-10mL, 10d-10mL, 11d-7mL, 12d-7mL, 13d-7mL, 14d-7mL, 15d-5mL; Pastille percolating fluid-10 ℃ freezing preservation supplies assay to use.
6, collect the pastille percolating fluid for the last time after, finish the seepage flow experiment, close the setting of thermostatical storehouse temperature, stripping assembly.Get residual medicine carrying embedded material, weigh, weight is 1.225g, and 4 ℃ of stored refrigerated supply assay to use.
7, get the pastille percolating fluid of step 5, and the residual medicine carrying embedded material of step 6, adopt high performance liquid chromatography, carry out the vancomycin assay.
8, data analysis: according to percolating fluid Chinese traditional medicine assay result, calculate drug concentration, medicine accumulative total burst size, the result sees table.The accumulative total burst size of vancomycin is 220.72mg, accounts for 22.71% of medicine carrying total amount (972.03mg).Curve when drawing medicine is shown in Fig. 3 and table 1.
Vancomycin assay result in table 1: the embodiment 1 pastille drainage liquid
| Numbering | Sample time (my god) | Draining fluids amasss (mL) | Drug concentration (mg/L) | Accumulative total burst size (mg) |
| 1 | 0.5 | 141 | 220.80 | 17.03 |
| 2 | 1 | 140 | 286.39 | 71.23 |
| 3 | 2 | 200 | 455.21 | 162.27 |
| 4 | 3 | 29 | 487.74 | 176.41 |
| 5 | 4 | 29 | 492.08 | 190.68 |
| 6 | 5 | 28 | 391.75 | 201.65 |
| 7 | 6 | 14 | 365.39 | 206.77 |
| 8 | 7 | 11 | 280.71 | 209.86 |
| 9 | 8 | 11 | 274.79 | 212.88 |
| 10 | 9 | 10 | 242.58 | 215.31 |
| 11 | 10 | 10 | 192.05 | 217.23 |
| 12 | 11 | 7 | 155.44 | 218.31 |
| 13 | 12 | 7 | 98.06 | 219.00 |
| 14 | 13 | 7 | 93.07 | 219.65 |
| 15 | 14 | 7 | 91.35 | 220.09 |
| 16 | 15 | 5 | 85.69 | 220.72 |
Seepage flow finishes the back and measures the vancomycin content in the residual embedded material, measures the result for containing vancomycin 0.284g in every 1g retained material, and calculating residual dose is 347.92mg, accounts for 35.79% of medicine carrying total amount (972.03mg).
1, preparation percolating fluid: get physiological saline, 1000mL adopts cryoscopic method to measure osmotic pressure altogether, and osmotic pressure is: 311mOsm/kg; Adopt acidometer to measure the pH value, the pH value is 7.0, opens rearmounted 4 ℃ of stored refrigerated, and is subsequent use.
2, preparation medicine carrying embedded material:
Get vancocin vial powder-injection (trade name Vancomycin) 2g, other takes by weighing calcium sulphate artificial bone (OSTEOSET, U.S. WRIGHT medical skill group) 3g, mixes, and stirs; Other takes by weighing Cemex XL, and (Italy) bone cement 3g mixes the vancomycin mixture of calcium sulfate with bone cement for Tecres SpA, Verona, fully stirs; Add thinning agent 5mL, fully stirring reaction; Potpourri is placed the ultrasonic Extraction appearance, and ultrasonic 3min is to get rid of bubble; Medicine carrying bone cement slurries are evenly injected the 1mL syringe of pulling out injection putter, and above-mentioned bone cement slurry can be filled 4 1mL syringes; Bubble is got rid of in vibration; Treat to remove syringe after bone cement solidifies, promptly obtain the about 6mm of diameter, cylindric medicine carrying embedded material 1-1,1-2,1-3 and the 1-4 of the about 8cm of length.Weigh, weight is respectively: 1-1,3.235g, 1-2,3.233g, 1-3,3.259g and 1-4,3.214g.Get 2-1 medicine carrying embedded material, carry out the vancomycin assay, the assay result is: contain vancomycin 0.145g in every 1g medicine carrying embedded material, the release behavior experiment of the outer topical remedy of all the other medicine carrying vegetable material donors.
3, get 1-2 medicine carrying embedded material in the step 2; The bottom, material storehouse of packing into; With bolt top, material storehouse and bottom, material storehouse are coupled together, and place thermostatical storehouse, will add liquid chamber, flow control valve, experiment material storehouse and receiving chamber through conduit at last and be connected in turn.
4, get the percolating fluid of step 1, add certainly in the filling opening of liquid chamber and add; Open the thermostatical storehouse outside the experiment material storehouse, water temperature is set to 37 ℃, and promptly human body temperature is kept the temperature constant state in experiment material storehouse; The adjusting percolation flow velocity is 0.2mL/min, beginning seepage flow.Percolation flow velocity adjustment program is: 1d, 0.2mL/min; 2d, 0.14mL/min; 3-5d, 0.02mL/min; 6d, 0.01mL/min; 7-10d, 0.008mL/min; 11-15d, 0.005mL/min.Regularly supply the percolating fluid in the charger in the flow event, guarantee to add liquid chamber and have the seepage flow that enough percolating fluids can continue.
5, begin 12h, 1,2,3,4,5,6,7,8,9,10,11,12,13,14 and 15d respectively at seepage flow, open the receiving chamber liquid outlet, collect the pastille percolating fluid, collect back seal fluid outlet; The pastille percolating fluid of collecting, metered volume is: 12h-140mL, 1d-140mL, 2d-198mL, 3d-29mL, 4d-29mL, 5d-28mL, 6d-15mL, 7d-11mL, 8d-10mL, 9d-10mL, 10d-10mL, 11d-7mL, 12d-7mL, 13d-7mL, 14d-7mL, 15d-5mL; Pastille percolating fluid-10 ℃ freezing preservation supplies assay to use.
6, collect the pastille percolating fluid for the last time after, seepage flow experiment finishes, and closes the setting of thermostatical storehouse temperature, stripping assembly.Get residual medicine carrying embedded material, weigh, weight is 1.097g, and 4 ℃ of stored refrigerated supply assay to use.
7, get the pastille percolating fluid of step 5, and the residual medicine carrying embedded material of step 6, adopt high performance liquid chromatography, carry out the vancomycin assay.
8, data analysis: according to percolating fluid Chinese traditional medicine assay result, calculate drug concentration, medicine accumulative total burst size, the result sees table.The accumulative total burst size of vancomycin is 178.05mg, accounts for 37.96% of medicine carrying total amount (469.08mg).Curve when drawing medicine is shown in Fig. 4 and table 2.
Vancomycin assay result in table 2: the embodiment 2 pastille drainage liquid
| Numbering | Sample time (my god) | Draining fluids amasss (mL) | Drug concentration (mg/L) | Accumulative total burst size (mg) |
| 1 | 0.5 | 140 | 161.06 | 22.55 |
| 2 | 1 | 140 | 174.81 | 47.02 |
| 3 | 2 | 198 | 415.41 | 129.27 |
| 4 | 3 | 29 | 454.29 | 142.45 |
| 5 | 4 | 29 | 359.19 | 152.86 |
| 6 | 5 | 28 | 351.68 | 162.71 |
| 7 | 6 | 15 | 286.54 | 167.01 |
| 8 | 7 | 11 | 251.49 | 169.78 |
| 9 | 8 | 10 | 192.66 | 171.70 |
| 10 | 9 | 10 | 180.45 | 173.51 |
| 11 | 10 | 10 | 135.21 | 174.86 |
| 12 | 11 | 7 | 99.74 | 175.56 |
| 13 | 12 | 7 | 94.84 | 176.22 |
| 14 | 13 | 7 | 95.36 | 176.89 |
| 15 | 14 | 7 | 102.13 | 177.60 |
| 16 | 15 | 5 | 89.09 | 178.05 |
Seepage flow finishes the back and measures the vancomycin content in the residual embedded material, measures the result for containing vancomycin 0.171g in every 1g retained material, and calculating residual dose is 39.99%.
1, preparation percolating fluid: get physiological saline, 1000mL adopts cryoscopic method to measure osmotic pressure altogether, and osmotic pressure is: 312mOsm/kg; Adopt acidometer to measure the pH value, the pH value is 7.0, opens rearmounted 4 ℃ of stored refrigerated, and is subsequent use.
2, preparation medicine carrying embedded material:
Get the vancocin vial powder-injection (trade name Vancomycin 1.2g, other takes by weighing calcium sulphate artificial bone (OSTEOSET, U.S. WRIGHT medical skill group) 3g, mixes, and stirs; Other takes by weighing Cemex XL, and (Italy) bone cement 3g mixes the vancomycin mixture of calcium sulfate with bone cement for Tecres SpA, Verona, fully stirs; Add thinning agent 4.5mL, fully stirring reaction; Potpourri is placed the ultrasonic Extraction appearance, and ultrasonic 3min is to get rid of bubble; Medicine carrying bone cement slurries are evenly injected the 1mL syringe of pulling out injection putter, and above-mentioned bone cement slurry can be filled 4 1mL syringes; Bubble is got rid of in vibration; Treat to remove syringe after bone cement solidifies, promptly obtain the about 6mm of diameter, cylindric medicine carrying embedded material 1-1,1-2,1-3 and the 1-4 of the about 8cm of length.Weigh, weight is respectively: 1-1,2.505g, 1-2,2.533g, 1-3,2.659g and 1-4,2.614g.Get 1-1 medicine carrying embedded material, carry out the vancomycin assay, the assay result is: contain vancomycin 0.117g in every 1g medicine carrying embedded material, the release behavior experiment of the outer topical remedy of all the other medicine carrying vegetable material donors.
3, get 1-2 medicine carrying embedded material in the step 2; The bottom, material storehouse of packing into; With bolt top, material storehouse and bottom, material storehouse are coupled together, and place thermostatical storehouse, will add liquid chamber, flow control valve, experiment material storehouse and receiving chamber through conduit at last and be connected in turn.
4, get the percolating fluid of step 1, add certainly in the filling opening of liquid chamber and add; Open the thermostatical storehouse outside the experiment material storehouse, water temperature is set to 37 ℃, and promptly human body temperature is kept the temperature constant state in experiment material storehouse; The adjusting percolation flow velocity is 0.2mL/min, beginning seepage flow.Percolation flow velocity adjustment program is: 1d, 0.2mL/min; 2d, 0.14mL/min; 3-5d, 0.02mL/min; 6d, 0.01mL/min; 7-10d, 0.008mL/min; 11-15d, 0.005mL/min.Regularly supply the percolating fluid in the charger in the flow event, guarantee to add liquid chamber and have the seepage flow that enough percolating fluids can continue.
5, begin 12h, 1,2,3,4,5,6,7,8,9,10,11,12,13,14 and 15d respectively at seepage flow, open the receiving chamber liquid outlet, collect the pastille percolating fluid, collect back seal fluid outlet; The pastille percolating fluid of collecting, metered volume is: 12h-140mL, 1d-140mL, 2d-200mL, 3d-29mL, 4d-28mL, 5d-28mL, 6d-14mL, 7d-11mL, 8d-10mL, 9d-10mL, 10d-10mL, 11d-7mL, 12d-7mL, 13d-7mL, 14d-7mL, 15d-5mL; Pastille percolating fluid-10 ℃ freezing preservation supplies assay to use.
6, collect the pastille percolating fluid for the last time after, seepage flow experiment finishes, and closes the setting of thermostatical storehouse temperature, stripping assembly.Get residual medicine carrying embedded material, weigh, weight is 1.025g, and 4 ℃ of stored refrigerated supply assay to use.
7, get the pastille percolating fluid of step 5, and the residual medicine carrying embedded material of step 6, adopt high performance liquid chromatography, carry out the vancomycin assay.
8, data analysis: according to percolating fluid Chinese traditional medicine assay result, calculate drug concentration, medicine accumulative total burst size, the result sees table 1.The accumulative total burst size of vancomycin is 165.48mg, accounts for 56.48% of medicine carrying total amount.Curve when drawing medicine is shown in Fig. 5 and table 3.
Vancomycin assay result in table 3: the embodiment 3 pastille drainage liquid
Seepage flow finishes the back and measures the vancomycin content in the residual embedded material, measures the result for containing vancomycin 0.0781g in every 1g retained material, and calculating residual dose is 27.31%.
It is visible to measure the result by above-mentioned case study on implementation; According to present clinical experience scheme: carrier-vancomycin dosage (6g-4g) is implemented, and percolating fluid Chinese traditional medicine concentration is much higher than the effective Mlc of medicine, and drug residue is bigger; Employing apparatus of the present invention experimentize; Adjustment carrier-vancomycin dosage (6g-1.2g), the percolating fluid drug concentration has met and exceeded effective Mlc, can realize continuing antibacterial effect; Reduce the potential spinoff that causes because of drug dose is excessive simultaneously, and reduce the medicine expense.
The foregoing description is used for the present invention that explains, rather than limits the invention, and in the protection domain of spirit of the present invention and claim, any modification and change to the present invention makes all fall into protection scope of the present invention.
Claims (3)
1. the experimental provision of aids drug local delivery of drug behavior; It is characterized in that; It comprises: add liquid chamber (1), flow control valve (2), experiment material storehouse (3) and receiving chamber (4) etc., add liquid chamber (1), flow control valve (2), experiment material storehouse (3) and receiving chamber (4) and be connected through conduit successively.
2. according to the experimental provision of the said aids drug local delivery of drug of claim 1 behavior; It is characterized in that; Said experiment material storehouse (3) comprises thermostatical storehouse (5), top, material storehouse (6) and bottom, material storehouse (7); Top, material storehouse (6) and bottom, material storehouse (7) are hollow structure, and top, material storehouse (6) links to each other with flow control valve (2) through conduit, and bottom, material storehouse (7) links to each other with receiving chamber (4) through conduit; Top, material storehouse (6) and bottom, material storehouse (7) can link into an integrated entity through bolt, and place in the thermostatical storehouse (5).
3. the application of the experimental provision of the said aids drug local delivery of drug of claim 1 behavior; It is characterized in that; The experimental provision of aids drug local delivery of drug behavior is used to study the external topical remedy release behavior of medicine carrying embedded material; Understand the local drug concentration of different time, obtain drug release rate and accumulative total burst size, for clinical practice provides experimental data.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012102236471A CN102721796A (en) | 2012-06-27 | 2012-06-27 | Experimental device for simulating local drug release behavior of medicine and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012102236471A CN102721796A (en) | 2012-06-27 | 2012-06-27 | Experimental device for simulating local drug release behavior of medicine and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102721796A true CN102721796A (en) | 2012-10-10 |
Family
ID=46947616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012102236471A Pending CN102721796A (en) | 2012-06-27 | 2012-06-27 | Experimental device for simulating local drug release behavior of medicine and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102721796A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108956897A (en) * | 2018-08-29 | 2018-12-07 | 西安石油大学 | A kind of slow-release tracer sustained release rate measurement experiment device and experimental method |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807115A (en) * | 1996-01-31 | 1998-09-15 | Hu; Oliver Yoa-Pu | Dissolution apparatus simulating physiological gastrointestinal conditions |
| JP2000249696A (en) * | 1999-03-03 | 2000-09-14 | Nippon Oruganon Kk | Novel elution tester, and measuring apparatus including the same and elution test method |
| WO2001016582A1 (en) * | 1999-08-30 | 2001-03-08 | Euro-Celtique S.A. | In situ methods for measuring the release of a substance from a dosage form |
| CN101221160A (en) * | 2007-01-09 | 2008-07-16 | 浙江中医药大学 | Pulsation circulation type transdermal experiment instrument |
| CN201107302Y (en) * | 2007-09-21 | 2008-08-27 | 西安康业生物医疗设备科技有限公司 | Artificial labour medicament content test analyzer |
| CN101288781A (en) * | 2008-04-10 | 2008-10-22 | 浙江大学 | Method for promoting topical drug release on bone cement carried with antibiotics |
| CN101430311A (en) * | 2008-11-11 | 2009-05-13 | 重庆大学 | Medicine release measuring equipment and method for medicine eluting vascular inner rack |
| CN102090876A (en) * | 2011-03-04 | 2011-06-15 | 上海交通大学 | In-vitro magnetic-controlled medicament delivery capsule system based on wireless energy supply |
| CN202196058U (en) * | 2011-09-20 | 2012-04-18 | 中国中医科学院中药研究所 | Medicine absorber |
| CN202649199U (en) * | 2012-06-27 | 2013-01-02 | 浙江省中医药研究院 | Experiment equipment for simulating partial release action of drug |
-
2012
- 2012-06-27 CN CN2012102236471A patent/CN102721796A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807115A (en) * | 1996-01-31 | 1998-09-15 | Hu; Oliver Yoa-Pu | Dissolution apparatus simulating physiological gastrointestinal conditions |
| JP2000249696A (en) * | 1999-03-03 | 2000-09-14 | Nippon Oruganon Kk | Novel elution tester, and measuring apparatus including the same and elution test method |
| WO2001016582A1 (en) * | 1999-08-30 | 2001-03-08 | Euro-Celtique S.A. | In situ methods for measuring the release of a substance from a dosage form |
| CN101221160A (en) * | 2007-01-09 | 2008-07-16 | 浙江中医药大学 | Pulsation circulation type transdermal experiment instrument |
| CN201107302Y (en) * | 2007-09-21 | 2008-08-27 | 西安康业生物医疗设备科技有限公司 | Artificial labour medicament content test analyzer |
| CN101288781A (en) * | 2008-04-10 | 2008-10-22 | 浙江大学 | Method for promoting topical drug release on bone cement carried with antibiotics |
| CN101430311A (en) * | 2008-11-11 | 2009-05-13 | 重庆大学 | Medicine release measuring equipment and method for medicine eluting vascular inner rack |
| CN102090876A (en) * | 2011-03-04 | 2011-06-15 | 上海交通大学 | In-vitro magnetic-controlled medicament delivery capsule system based on wireless energy supply |
| CN202196058U (en) * | 2011-09-20 | 2012-04-18 | 中国中医科学院中药研究所 | Medicine absorber |
| CN202649199U (en) * | 2012-06-27 | 2013-01-02 | 浙江省中医药研究院 | Experiment equipment for simulating partial release action of drug |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108956897A (en) * | 2018-08-29 | 2018-12-07 | 西安石油大学 | A kind of slow-release tracer sustained release rate measurement experiment device and experimental method |
| CN108956897B (en) * | 2018-08-29 | 2021-10-08 | 西安石油大学 | Experimental device and experimental method for measuring slow release rate of slow-release tracer |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2515869B1 (en) | Wound care products | |
| CN104519834B (en) | For treating compositions and the method in bone space and open fracture | |
| CN202649199U (en) | Experiment equipment for simulating partial release action of drug | |
| CN102721796A (en) | Experimental device for simulating local drug release behavior of medicine and application thereof | |
| MXPA05002589A (en) | Antibiotic microspheres for treatment of infections and osteomyelitis. | |
| Yin et al. | Diagnosis, management, and prevention of prosthetic joint infections | |
| CN100540066C (en) | Medical chitosan dressing and production method thereof | |
| CN202236501U (en) | Honey dressing for exchanging medicament of infective wound | |
| CN105079000B (en) | A kind of composition and its application, preparation | |
| CN101721422B (en) | Medicine for treating arthritis and preparation method thereof | |
| CN101584753B (en) | New medical use of Shenshitong preparation | |
| CN102697925A (en) | Traditional Chinese medicine combination for treating aural eczema | |
| CN107157924A (en) | Naproxen sodium sodium chloride injection and preparation method thereof | |
| CN104784167B (en) | A kind of medicine for treating animal eperythrozoonosis and preparation method thereof | |
| Shen et al. | Chronic osteomyelitis treatment: a clinical and pharmaco-kinetic study of vancomycin impregnated calcium sulphate | |
| Hanafiah et al. | The effect of topical application of 3% binahong (Anredera cordifolia (Ten) Steenis) leaves extract gel on the radiographic bone density in post-extraction socket | |
| CN101773516A (en) | Acidic buffer gel preparation for vaginas and preparation method and application thereof | |
| CN101549049B (en) | Chinese medicinal combination for treating acute nephritis and chronic nephritis | |
| Azi et al. | Bone cement and gentamicin in the treatment of bone infection: background and in vitro study | |
| CN109045044A (en) | A kind of compound medicine and preparation method thereof, purposes | |
| CN112107621B (en) | Plant essence for preventing bedsore and deodorizing and application thereof | |
| Shormanov et al. | Opportunities of drugs based on D-mannose and herbal components in the treatment and prevention of recurrent lower urinary tract infections in women | |
| Lischer et al. | Post‐operative Complications | |
| CN102133154B (en) | Root apex filling material and preparation method thereof | |
| RU2668692C1 (en) | Powder pharmaceutical form for relief acceleration of osteomyelitis containing chloride rubidium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20121010 |