CN107456665B - A kind of degradable conduit for loading drug particle - Google Patents
A kind of degradable conduit for loading drug particle Download PDFInfo
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- CN107456665B CN107456665B CN201710823668.XA CN201710823668A CN107456665B CN 107456665 B CN107456665 B CN 107456665B CN 201710823668 A CN201710823668 A CN 201710823668A CN 107456665 B CN107456665 B CN 107456665B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
- A61N5/1002—Intraluminal radiation therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L29/126—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/148—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0021—Catheters; Hollow probes characterised by the form of the tubing
- A61M25/0023—Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0043—Catheters; Hollow probes characterised by structural features
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
- A61N5/1007—Arrangements or means for the introduction of sources into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/02—General characteristics of the apparatus characterised by a particular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
- A61N5/1007—Arrangements or means for the introduction of sources into the body
- A61N2005/101—Magazines or cartridges for seeds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
- A61N2005/1019—Sources therefor
- A61N2005/1024—Seeds
Abstract
The invention belongs to medical instruments fields, more particularly to a kind of degradable conduit for loading drug particle, it is used to accommodate the first tube chamber and the second tube chamber of drug particle including connecting portion, set on the connecting portion both ends, the conduit realizes the connection between multiple conduits by drug particle, and it can ensure that the interval of drug particle in the catheter is consistent, while without in addition increasing spacer block in conduit, install and easy to operate, production is low with operating cost, suitable for promoting and applying on a large scale.In addition, the connecting portion, the first tube chamber and the second tube chamber in conduit of the present invention are made of β chitosans/lactic acid composite material, which is degradation material, and degradation time is short, and hydrophily is good.
Description
Technical field
The invention belongs to medical instruments fields, and in particular to a kind of degradable tremie method for loading drug particle.
Background technology
For oncotherapy, tumour cell will effectively be killed by not requiring nothing more than, improve survival rate, while also need to ensure to suffer from
The life quality of person.And the mode of traditional systemic administration antineoplaston has half-life short, is difficult to remain effective for a long time
Concentration, general toxicity be big and patient tolerance can force difference the defects of.It can not only be improved in a manner that drug implantation is locally placed
The drug concentration of tumour target position reduces drug dose while increasing curative effect of medication, thereby reduces the adverse reaction of drug
And general toxic reaction.But by the accurate implantation tumour position of drug and meet rational position planning, implant procedure difficulty
Greatly, time-consuming, even needs secondary implantation sometimes, increases wound and the risk for the treatment of, increases the pain of patient.
Therefore, a kind of degradable implantable conduit of particle for loading drug, conduit can carry a certain amount of anti-swollen
Tumor medicine seeds implanted is to tumor locus, and drug particle position in tumour is fixed, and drug particle has fixed position
Interval, it is achieved thereby that the reasonable layout of drug particle, drug is able to play maximum therapeutic effect.And with the contracting of tumour
Small, degradable conduit can be reduced and be degraded therewith, reduce injury and the toxic side effect of normal tissue.Such as Chinese patent application
CN105498073A discloses a kind of degradable implantation catheter for carrying drug particle, including accommodating the catheter body of drug and setting
In the spacer block for being spaced apart drug in catheter body, catheter body and spacer block are made of degradation material, still
The conduit needs to increase spacer block in the catheter, undoubtedly increases the time of degradation.
Since polylactic acid has good biocompatibility, bioactivity and mechanical property, it has also become biodegradable medical
One of most-often used material in Material Field.But numerous studies show poly-lactic acid material that there are following in practical applications
Problem：1) hydrophily is inadequate, weaker to sticking for cell；2) degradation speed is slow, and degradation soak time is very long (general 3~5 years).
Therefore, in order to improve the quality of medical material, it is necessary to take into account research and develop a kind of new material, have compared with
Good hydrophily, and degradation speed is fast.
Invention content
The present invention is intended to provide a kind of degradable conduit for loading drug particle, the conduit can be packed into the iodo- of national standard
125 seed sources and the antitumor drug of slow releasing medicinal composition granule such as fluorouracil slow release particle etc..It is packed into the conduit implantation tumour of drug
Behind region, fixed function is played during medicament slow release or particle radiation therapy, drug or particle is prevented to be subjected to displacement influence
Therapeutic effect.In addition, the degradable conduit is prepared by β-chitosan/lactic acid composite material, has hydrophily good, drop
It is short to solve the period.
In order to achieve the above object, the present invention uses following technical scheme：A kind of degradable conduit for loading drug particle,
It is used to accommodate the first tube chamber and the second tube chamber of drug particle including connecting portion, set on the connecting portion both ends.The connecting portion is used
In connecting the first tube chamber and the second tube chamber, connecting portion functions only as the effect of connection, shape can be arbitrary, as long as can
The purpose for realizing the first tube chamber of connection and the second tube chamber is belonged in the scope of connecting portion of the present invention, it is preferable that connecting portion
It is preferably cylindric, it is highly preferred that a diameter of 0.8-1.8mm of connecting portion.The length of connecting portion is preferably 10-40mm.
Further, compared with prior art, one of innovation is conduit of the present invention, can pass through drug grain
Son is realized and connects multiple conduits, while can keep being spaced consistent, installation between drug particle without being further added by spacer block
It is convenient and simple, reduce production cost and operating cost.And to achieve these goals, the first tube chamber and the second tube chamber and drug
The length of particle must strictly have following relationship：The length of first tube chamber and the second tube chamber is the 1/2 drug particle length,
The average wall thickness of first tube chamber and the second tube chamber is 0.05-0.15mm, internal diameter 0.8-1.8mm.In actual load process
In, drug particle is first fixed on to the first tube chamber of conduit a, 1/2 length of drug particle then takes in the first tube chamber at this time
Conduit b makes other 1/2 length of drug particle be fixed on the second tube chamber of drug catheter b, so as to fulfill the company of two conduits
It connects, the connection of n conduit can refer to above-mentioned mounting means.
Further, first tube chamber and the second tube chamber are fixed with drug particle by the way of interference fit, described
Fixed form can for bar shaped extruding, fixed, cross extruding be fixed, inclined-plane extruding is fixed or protruding circular ring squeezes fixation.
Further, the connecting portion, the first tube chamber and the second tube chamber are by β-chitosan/lactic acid composite material system
Into.
Further, above-mentioned β-chitosan/lactic acid composite material is made by following steps：
A) the preparation of polylactic acid：It includes two steps of S1~S2：
The preparation of S2, lactide：Using content as the D of 85wt%, Pfansteihl is raw material, and dry oxidation zinc is catalyst, is added
Heat is warming up to 100~120 DEG C, and then vacuum distillation is brought rapidly up to 200~250 DEG C, be evaporated under reduced pressure, the fraction second steamed
Acetoacetic ester is washed and recrystallized to get D, L- lactides；
S2, synthesizing polylactic acid：The D that above-mentioned steps are prepared is weighed, L- lactides are placed in clean ampere bottle, injection
The chloroform soln of the stannous octoate of 0.1~0.3% mass of D, L- lactide makees initiator, vacuumizes, bottleneck fusing sealing,
It is placed in the oil bath of 130~160 DEG C of temperature, polymerize 5~50h, that is, obtain the polylactic acid that number-average molecular weight is 6~100,000；
B) the preparation of composite material：The above-mentioned polylactic acid being prepared is taken, is dissolved in organic solvent ethyl acetate, ultrasonic wavelength-division
Dissipate, add in β-chitosan, ultrasonic wave dispersion to get.
It is tasted for hydrophily existing for previously described single poly-lactic acid material and the long problem of degradation time, inventor
Examination introduces hydrophilic radical, although the problems such as obtained degradation material hydrophily is improved largely, but degradation time is long still
It can not be resolved.In other words, only introducing hydrophilic radical can not solve the above problems, but be needed in itself in view of implantation material
Have the characteristics such as nontoxicity, good biocompatibility, therefore the ingredient introduced is more, it is more complicated to be also just very likely difficult to protect
Hold the original biocompatibility of material.
β-chitosan is a kind of unique positively charged alkaline polysaccharide, nontoxic, non-stimulated, bio-compatible in nature
Property, biological degradability are good, are widely used in organizational project.More importantly β-chitosan has high-hydrophilic.
Therefore, inventor attempts to add β-chitosan in polylactic acid, and it is compound that a kind of β-chitosan/polylactic acid is prepared
Material is that after adding in β-chitosan, the hydrophilicity of material has compared with single poly-lactic acid material significantly to be carried unexpectedly
Height is investigated by the degradation property to composite material and found, degradation rate is significantly improved, that is to say, that β-chitosan
Addition not only improves polylactic acid hydrophily, promotes the degradation of polylactic acid, achieves unexpected technique effect.
Inventor had also discovered during experiment one it is interesting the phenomenon that, remaining two kinds of configuration of chitosan, α-shell
The addition of glycan and γ-chitosan can not but obtain the effect as β-chitosan.Experiment is found, adds in α-chitosan
And although γ-chitosan improves the hydrophilic sex chromosome mosaicism of composite material, makes us feeling surprised, add in α-configuration and
After the chitosan of γ-configuration, the degradation speed of composite material is reduced, that is to say, that the chitosan of α-configuration and γ-configuration
Although addition can also improve the hydrophilic sex chromosome mosaicism of composite material, can not solve the problems, such as that polylactic acid degradation time is long,
It even can also extend the degradation time of material.
The present invention has the following advantages：
1) the present invention provides a kind of degradable conduit for loading drug particle, multiple lead is realized by drug particle
Connection between pipe, and can ensure that the interval of drug particle in the catheter is consistent, while without in addition increasing interval in conduit
Block is installed and easy to operate, and production is low with operating cost, suitable for promoting and applying on a large scale.
2) the present invention provides a kind of β-chitosan/polylactic acid degradable material, with previous degradable poly lactate material phase
Than hydrophily is good, and degradation time is short.
Description of the drawings
Fig. 1 is the schematic diagram of the degradable conduit of the present invention；
Fig. 2 is the assembling schematic diagram that two degradable conduits load drug particle；
Fig. 3 is the assembling schematic diagram that three degradable conduits load drug particle；
Fig. 4 is the fixed form schematic diagram of drug particle of the present invention and conduit；
Fig. 5 is 1 group of back part of animal section CT figure of embodiment；
Fig. 6 is 1 group of back part of animal front CT figure of embodiment.
In figure：1st, connecting portion；2nd, the first tube chamber；3rd, the second tube chamber；4th, drug particle；
201 first tube chambers；301 second tube chambers.
Specific embodiment
The specific embodiment of form by the following examples makees further specifically the above of the present invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to following embodiment.
The preparation of embodiment 1, β-chitosan/lactic acid composite material
A) the preparation of polylactic acid：It includes two steps of S1~S2：
The preparation of S2, lactide：Using content as the D of 85wt%, Pfansteihl is raw material, and dry oxidation zinc is catalyst, is added
Heat is warming up to 110 DEG C, and then vacuum distillation is brought rapidly up to 220 DEG C, be evaporated under reduced pressure, and the fraction steamed is washed with ethyl acetate
And it recrystallizes to get D, L- lactides；
S2, synthesizing polylactic acid：The D that above-mentioned steps are prepared is weighed, L- lactides are placed in clean ampere bottle, injection
The chloroform soln of the stannous octoate of 0.2% mass of D, L- lactide makees initiator, vacuumizes, and bottleneck fusing sealing is placed in
In the oil bath that 150 DEG C of temperature, it polymerize 25h, that is, obtains the polylactic acid that number-average molecular weight is 6.5 ten thousand；
B) the preparation of composite material：The above-mentioned polylactic acid being prepared is taken, is dissolved in organic solvent ethyl acetate, ultrasonic wavelength-division
Dissipate, add in β-chitosan, ultrasonic wave dispersion to get.
The preparation of comparative example 1, lactic acid composite material
Difference lies in be added without β-chitosan, remaining parameter and operation such as embodiment 1 to comparative example 1 with embodiment 1.
The preparation of comparative example 2, β-chitosan/lactic acid composite material
Comparative example 2 and embodiment 1 difference lies in：β-chitosan is replaced with α-chitosan, remaining parameter and operation are strictly according to the facts
Apply example 1.
The preparation of comparative example 3, β-chitosan/lactic acid composite material
Comparative example 3 and embodiment 1 difference lies in：β-chitosan is replaced with γ-chitosan, remaining parameter and operation are strictly according to the facts
Apply example 1.
Embodiment 2, the degradable conduit of the present invention
The embodiment of the present invention 1 provides a kind of degradable conduit for loading drug particle, including connecting portion 1, set on the company
Socket part both ends are used to accommodate the first tube chamber 2 and the second tube chamber 3 of drug particle 4.The connecting portion is for connection 301 He of the first tube chamber
Second tube chamber 302, connecting portion function only as the effect of connection, shape can be arbitrary, as long as connection first can be realized
The purpose of tube chamber and the second tube chamber is belonged in the scope of connecting portion of the present invention, it is preferable that and connecting portion is preferably cylindric,
Preferably, a diameter of 0.8-1.8mm of connecting portion, it is highly preferred that a diameter of 1.2mm of connecting portion.The length of connecting portion is preferred
For 10-40mm, more preferably 25mm.First tube chamber and the preferably cylindrical groove of the second tube chamber.
Further, compared with prior art, one of innovation is conduit of the present invention, can pass through drug grain
Son is realized and connects multiple conduits, while can keep being spaced consistent, installation between drug particle without being further added by spacer block
It is convenient and simple, reduce production cost and operating cost.And to achieve these goals, the first tube chamber and the second tube chamber and drug
The length of particle must strictly have following relationship：The length of first tube chamber and the second tube chamber is the 1/2 drug particle length,
The average wall thickness of first tube chamber and the second tube chamber is 0.05-0.15mm, internal diameter 0.8-1.8mm.In actual load process
In, drug particle is first fixed on to the first tube chamber of conduit a, 1/2 length of drug particle then takes in the first tube chamber at this time
Conduit makes other 1/2 length of drug particle be fixed on the second tube chamber of drug catheter b, so as to fulfill the connection of two conduits,
The connection of n conduit can refer to above-mentioned mounting means.
First tube chamber and the second tube chamber are fixed with drug particle by the way of interference fit, and the fixed form can
Think that bar shaped extruding is fixed, cross extruding is fixed, inclined-plane extruding is fixed or protruding circular ring squeezes fixation.The connecting portion, first
Tube chamber and the second tube chamber β-chitosan/lactic acid composite material as described in embodiment 1 are made.
Influence of the chitosan to composite material hydrophilicity of test example one, various configuration
By investigating embodiment 1, the contact angle of degradable conduit that 1~3 composite material of comparative example is prepared with
And absorptivity carrys out the hydrophilicity of evaluating combined material, the former reflects moment parent/hydrophobicity during material surface contact water, then
Person reflects the parent/hydrophobicity of material surface and inside subject in a long time, and the two combines characterization material and has more reasonability.
Measured using contact angle meter by the conduit that above-mentioned composite material is prepared to the contact angle of water, and take the conduits of phase homogenous quantities in
It is placed in distilled water to impregnate at room temperature and take out afterwards for 24 hours, weigh after the water of catheter surface is blotted with filter paper, calculate water absorption rate, as a result
As shown in table 1.
1 contact angle of table and water absorption rate
| Group | Contact angle (°) | Water absorption rate (%) |
| Embodiment 1 | 65.6 | 55.2 |
| Comparative example 1 | 113.5 | 11.4 |
| Comparative example 2 | 68.5 | 48.5 |
| Comparative example 3 | 71.9 | 52.9 |
As shown in Table 1, the chitosan of three kinds of configurations and the compound material being prepared of polylactic acid are added in, with being added without phase
Than contact angle significantly becomes smaller, and water absorption rate dramatically increases, that is to say, that the chitosan of three kinds of configurations can significantly improve composite wood
The hydrophily of material, difference is little between each group.
Test the influence of chitosan external degradation property to composite material of two, various configuration
Each group conduit is prepared in Example 1,1~3 composite material of comparative example, places a catheter in 37 DEG C of physiology
In brine, a sample is taken every 7d, surveys its weight-loss ratio, test result is as shown in table 2.
Weight-loss ratio=(m1-m2)/m1* 100%
Influence of the chitosan of 2 various configuration of table to material degradation performance
As can be seen from Table 2, compared with being added without chitosan, β-chitosan is added in, the drop of material can be significantly increased
Rate is solved, the weight-loss ratio for being placed in material after 42d in PBS buffer solutions reaches 21.54%.And make us be with feeling surprised, α-
The degradation efficiency for adding in there is no above-mentioned effect or even also reducing material of the chitosan of configuration and γ-configuration.
Experiment three, Implantation Test
3.1 test method
3.1.1 animal：48 healthy adult new zealand rabbits, half male and half female are chosen, 2.0~2.5kg of weight is randomly divided into 4
Group (1 group of embodiment, 1~3 group of comparative example), is divided into 4 animal observation periods, every group of each 3 New Zealand of observation period by every group 12
Rabbit, 4 observation periods are respectively 2 weeks, 4 weeks, 8 weeks and 10 weeks.
3.1.2 material：The degradable conduit that embodiment 1 and 1~3 composite material of comparative example are prepared.
3.1.3 method：Every group of animal is anaesthetized, in rabbit ridge after medicinal alcohol sterilizes using yellow Jackets auricular vein
Make skin incision at the about 4cm of column both sides, degradable led what embodiment 1 and 1~3 composite material of comparative example were prepared
Pipe is implanted into respectively in each group rabbit back musculature, and suture, the surface of a wound commonly sterilizes.
3.1.4 degradation effect measures in body：Respectively at postoperative 2 weeks, 4 weeks, 8 weeks and 10 weeks euthanasia animals, cut
Implantation catheter measures the variation of vessel element amount, evaluates internal degradation effect.
3.1.5 drug particle fixing situation is evaluated：In postoperative the 10th week, 1 group of animal of euthanasia embodiment, CT scan
Back part of animal, the fixing situation of observation drug particle in vivo, as a result as shown in Figure 5 and Figure 6.
3.2 interpretation of result
3.2.1 degradation effect measures in body
As can be seen from the above table, degradable conduit provided by the invention is implanted into degradable after 10 weeks in animal body；
And degradable conduit made from β-chitosan is added without, degradation efficiency significantly decreases, and after implanting 10 weeks, degradation rate is
65.40%；In addition, the degradable conduit that the chitosan for adding in remaining two kinds of configuration is prepared, surprisingly, its
Degradation effect in vivo has pole to be remarkably decreased or even lower than being added without β-chitosan compared with adding in β-chitosan, also
It is to say, the addition of the chitosan of remaining two kinds of configuration can not improve the degradation efficiency of poly-lactic acid material, can also reduce it on the contrary
Degradation rate.
3.2.2 particle fixing situation
The luminous point of 3 proper alignments is drug particle in a-quadrant in Fig. 5, and as can be seen from Figure 5 drug particle is being led
Marshalling in pipe, fixing situation is good in vivo for conduit；It can be seen that the white of some proper alignments in B area from Fig. 6
Point, it is also seen that drug particle proper alignment in the catheter, fixing situation is good in vivo for conduit.
The above-described embodiments merely illustrate the principles and effects of the present invention, and is not intended to limit the present invention.It is any ripe
The personage for knowing this technology all can carry out modifications and changes under the spirit and scope without prejudice to the present invention to above-described embodiment.Cause
This, those of ordinary skill in the art is complete without departing from disclosed spirit and institute under technological thought such as
Into all equivalent modifications or change, should by the present invention claim be covered.
Claims (8)
1. a kind of degradable conduit for loading drug particle, which is characterized in that used including connecting portion, set on the connecting portion both ends
In the first tube chamber and the second tube chamber that accommodate drug particle；The length of first tube chamber be the 1/2 drug particle length, institute
The average wall thickness for stating the first tube chamber is 0.05-0.15mm, internal diameter 0.8-1.8mm；The length of second tube chamber is described in 1/2
Drug particle length, the average wall thickness of second tube chamber is 0.05-0.15mm, internal diameter 0.8-1.8mm.
2. degradable conduit as described in claim 1, which is characterized in that the connecting portion be length be 10-40mm, it is a diameter of
The cylinder of 0.8-1.8mm.
3. the degradable conduit as described in right 1, which is characterized in that first tube chamber and the second tube chamber are used with drug particle
The mode of interference fit is fixed.
4. the degradable conduit as described in right 3, which is characterized in that the fixed form squeezes fixed, cross for bar shaped and squeezes
Fixed, inclined-plane squeezes one kind during the extruding of fixed and protruding circular ring is fixed.
5. the degradable conduit as described in right 1, which is characterized in that the drug particle is antitumor drug.
6. the degradable conduit as described in right 5, which is characterized in that the antitumor drug is urinated for iodine-125 sealed seed source or fluorine
Pyrimidine slow-releasing granules.
7. the degradable conduit as described in right 1, which is characterized in that the connecting portion, the first tube chamber and the second tube chamber by
β-chitosan/lactic acid composite material is made.
8. the degradable conduit as described in right 7, which is characterized in that the β-chitosan/lactic acid composite material is by following step
It is rapid to be made：
A) the preparation of polylactic acid：It includes two steps of S1~S2：
The preparation of S2, lactide：Using content as the D of 85wt%, Pfansteihl is raw material, and dry oxidation zinc is catalyst, and heating rises
To 100~120 DEG C, then vacuum distillation is brought rapidly up to 200~250 DEG C temperature, be evaporated under reduced pressure, the fraction steamed acetic acid second
Ester is washed and recrystallized to get D, L- lactides；
S2, synthesizing polylactic acid：The D that above-mentioned steps are prepared is weighed, L- lactides are placed in clean ampere bottle, inject D, L-
The chloroform soln of the stannous octoate of 0.1~0.3% mass of lactide makees initiator, vacuumizes, and bottleneck fusing sealing is placed in
In the oil bath that 130~160 DEG C of temperature, it polymerize 5~50h, that is, obtains the polylactic acid that number-average molecular weight is 6~100,000；
B) the preparation of composite material：The above-mentioned polylactic acid being prepared is taken, is dissolved in organic solvent ethyl acetate, ultrasonic wave disperses,
Add in β-chitosan, ultrasonic wave dispersion to get.
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| CN102766268A (en) * | 2012-04-18 | 2012-11-07 | 上海市七宝中学 | Preparation method of antibacterial food packing material |
| CN102952263A (en) * | 2011-08-23 | 2013-03-06 | 国家纳米科学中心 | Graft polymer, and preparation method and use thereof |
| CN103251449A (en) * | 2005-10-13 | 2013-08-21 | 斯恩蒂斯有限公司 | Drug-impregnated encasement |
| CN105498073A (en) * | 2015-12-14 | 2016-04-20 | 中国人民解放军第三军医大学第一附属医院 | Degradable implantation catheter carrying drug particles |
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| CN103251449A (en) * | 2005-10-13 | 2013-08-21 | 斯恩蒂斯有限公司 | Drug-impregnated encasement |
| CN102952263A (en) * | 2011-08-23 | 2013-03-06 | 国家纳米科学中心 | Graft polymer, and preparation method and use thereof |
| CN102766268A (en) * | 2012-04-18 | 2012-11-07 | 上海市七宝中学 | Preparation method of antibacterial food packing material |
| CN105498073A (en) * | 2015-12-14 | 2016-04-20 | 中国人民解放军第三军医大学第一附属医院 | Degradable implantation catheter carrying drug particles |
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