CN110141760A - A kind of surface carries the vertebral plasty dilating sacculus and preparation method thereof of medicine - Google Patents
A kind of surface carries the vertebral plasty dilating sacculus and preparation method thereof of medicine Download PDFInfo
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- CN110141760A CN110141760A CN201910488081.7A CN201910488081A CN110141760A CN 110141760 A CN110141760 A CN 110141760A CN 201910488081 A CN201910488081 A CN 201910488081A CN 110141760 A CN110141760 A CN 110141760A
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- drug
- carried coat
- electrostatic spinning
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
- A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
- A61B17/88—Osteosynthesis instruments; Methods or means for implanting or extracting internal or external fixation devices
- A61B17/8802—Equipment for handling bone cement or other fluid fillers
- A61B17/8805—Equipment for handling bone cement or other fluid fillers for introducing fluid filler into bone or extracting it
- A61B17/8816—Equipment for handling bone cement or other fluid fillers for introducing fluid filler into bone or extracting it characterised by the conduit, e.g. tube, along which fluid flows into the body or by conduit connections
-
- 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
-
- 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
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
-
- 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
- A61M25/10—Balloon catheters
- A61M25/1027—Making of balloon catheters
-
- 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
- A61M29/00—Dilators with or without means for introducing media, e.g. remedies
- A61M29/02—Dilators made of swellable material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
- A61B2017/564—Methods for bone or joint treatment
-
- 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
- A61M2025/0008—Catheters; Hollow probes having visible markings on its surface, i.e. visible to the naked eye, for any purpose, e.g. insertion depth markers, rotational markers or identification of type
-
- 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
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
-
- 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
- A61M2210/00—Anatomical parts of the body
- A61M2210/10—Trunk
- A61M2210/1003—Spinal column
Abstract
The invention discloses the vertebral plasty dilating sacculus and preparation method thereof that a kind of surface carries medicine, it includes balloon body, has medicine carrying membrane on balloon body surface, the medicine carrying membrane is made of at least two layers of drug-carried coat, wherein, the first layer drug-carried coat directly contacted with balloon body is formed by electrostatic spinning.Medicine carrying membrane is arranged on balloon body surface in the present invention, medicine carrying membrane is made of the drug-carried coat of multilayer, medicine carrying membrane can retain in vivo after sacculus is withdrawn from, form the shell of package bone cement, both played the role of being released effectively drug to required position, improve the functioning efficiency of drug, play the role of preventing bone cement disengaging configuration again, function multi-panel, the postoperative effect for improving percutaneous vertbroplasty and Percutaneous kyplasty is particularly suitable for the treatment of osteoporosis and associated compression fracture.
Description
Technical field
The present invention relates to a kind of vertebroplasty dilating sacculus, and in particular to a kind of surface carries the vertebral plasty expansion of medicine
Sacculus and preparation method thereof belongs to percutaneous vertbroplasty the field of medical instrument technology.
Background technique
With the aggravation of social senilization's phenomenon, osteoporosis becomes a kind of common disease for endangering senior health and fitness.
Fracture healing process caused by osteoporosis is slow, and the risk of second fracture is big, and the quality of life of patient is significantly affected.
In 1984, Charles Robert Richet used percutaneous vertbroplasty (percutaneous vertebroplasty, PVP), warp first
Skin injection bone cement methyl methacrylate (polymethyl-methacrylate, PMMA) Lai Zengjia spinal stability delays
Patient pain is solved, prevents centrum from further collapsing.Later technique passes to the U.S., has developed percutaneous vertebral body on this basis
Convex plasty (percutaneous kyphoplasty, PKP) afterwards, is expanded in centrum using dilating sacculus, forms filling bone
The cavity of cement enhances the strength and stability of centrum, moreover it is possible to it reduces to neural compressing and stimulation, the pain of reduction of patient,
Improve the postoperative quality of life of patient.
But passing through the development of many years, Percutaneous kyplasty still has some shortcomings.Such as: bone cement is in injection
It is easy to happen leakage disperse, injuring nerve, vein or its hetero-organization；Bone cement is after supporting a period of time, with original centrum
Tissue connection is not close, and easily abjection is in situ；Osteoporosis causes bone density to reduce, bone loss and bone brittleness increase, and is easy
Second fracture and secondary fracture occurs.And the sacculus used in percutaneous vertbroplasty or Percutaneous kyplasty at present
Using materials such as polyethylene, polyethylene terephthalate, nylon, nylon elastomer (Pebax), polyurethane, polyether-polyurethanes
Material is made, and surface is smooth, is only able to achieve the effect that expansion in vivo forms cavity, above-mentioned deficiency can not be solved.
Other than percutaneous vertbroplasty, there are also some diseases therapy fields to need to use dilating sacculus, the most commonly used is
The interventional therapy field of the diseases such as coronary heart disease.In the interventional therapy of the diseases such as coronary heart disease, need to make using medicament elution sacculus
For in blood vessel, to play the role of reducing hemadostewnosis.Such as 2004, SeQuent®Please medicinal balloon for the first time will
The balloon surface that Iopromide and taxol are attached to, the treatment applied to restenosis in human body support.Later Kang- in 2017
Ju Lee etc. obtains sacculus and blood vessel the study found that micro texture is made to drug balloon surface by using blow molding process
The availability of institute's carrying medicament can be improved in bigger contact area.Similar, Chinese patent CN107088259A discloses one
Kind has the medicinal balloon structure of flap, 360 ° of load medicines, and the balloon surface when sacculus fills in flap can also contact blood vessel
And then discharge drug.Patent CN108853690A discloses a kind of design of film envelope drug storage sacculus, directly extrudes balloon surface
Surface texture, surface spray drug, reuse overlay film and closed, the overlay film rupture release medicine when sacculus fills in the blood vessel
Object.
The above sacculus is used in blood vessel, for the Special use Environment Design of blood vessel, although these sacculus tables
Face carries medicine, but is all to realize administration by the contact with drug with blood vessel, and drug can not be retained in for a long time affected part and play
The purpose of sustained release.
Chinese patent CN107596455A wraps up bone cement using a kind of netted sacculus of degradable macromolecule, leads to
The antibiotic property that nano-ZnO is added to realize material is crossed, the defect of the patent is: sacculus, which can not be expanded, raises cone shape into bone cement
Cavity is perfused, can not be closely knit by loose centrum Tissue approximation, thus it is poor to restore vertebral height aspect effect；And this is netted
Sacculus is not carried out load medicine, can not treat the osteoporosis cause of disease, and the incidence of secondary fracture is higher.Patent CN106726019A is public
A kind of minimally invasive fusion device of intervertebral spinal fusion nanometer biological glass coating has been opened, has realized retractility and mechanics branch using cochrome silk
Support, invests surface for nanometer biological glass coating and increases its biocompatibility, applied in fusion between foramen intervertebrale lens lower lumbar spine
Treat lumbar instability.The patent application field is different, is not carried out the function to form Cement fixation cavity and carry medicine.
From this point of view, presently disclosed sacculus effect is relatively simple, and still can satisfy without one kind prevents bone cement de-
Position, the sacculus guarantee sustained drug effect, improve bone density, reducing the multiple functions such as fracture probability of happening caused by osteoporosis
It is open.
Summary of the invention
Single deficiency is acted on for sacculus used in percutaneous vertbroplasty now or Percutaneous kyplasty,
The present invention provides the vertebral plasty dilating sacculus that a kind of surface carries medicine, which has medicine carrying membrane, and medicine carrying membrane exists
Sacculus can retain in vivo after withdrawing from, and form the shell of package bone cement, both played to required position and be released effectively drug
Effect, improve the functioning efficiency of drug, and play the role of preventing bone cement disengaging configuration, function multi-panel improves
The postoperative effect of percutaneous vertbroplasty and Percutaneous kyplasty is particularly suitable for osteoporosis and associated compression
Property fracture treatment.
The present invention also provides the preparation method that a kind of surface carries the vertebral plasty dilating sacculus of medicine, this method operation letters
It is single, easy to implement, it is convenient for industrialized production.
Specific technical solution of the present invention is as follows:
The present invention provides the vertebral plasty dilating sacculus that a kind of surface carries medicine, which carries the vertebral plasty dilating sacculus packet of medicine
Balloon body is included, has medicine carrying membrane on balloon body surface, the medicine carrying membrane is made of at least two layers of drug-carried coat, wherein
It is formed with the first layer drug-carried coat that balloon body directly contacts by electrostatic spinning.
Balloon body surface of the present invention has medicine carrying membrane, and the medicine carrying membrane is in balloon body pressurized expansion with balloon body one
Play expansion, when balloon body removes compression and back due to and the effect of interpyramidal stress and friction power separate with sacculus, still maintain
Shape in balloon body expansion, is retained in affected part and contacts with centrum tissue tight, medicine carrying membrane can be injected in such bone cement
In the cavity of package, medicine carrying membrane is equivalent to a shell of bone cement, and wrapping bone cement prevents it from leaking.
Further, the number of plies of the drug-carried coat can be carried out according to actual needs such as required medicament categories, drugloading rates
Selection and adjustment, are at least two layers, preferably 2-5 layers, such as 2 layers, 3 layers, 4 layers, 5 layers.In addition to first layer drug-carried coat is adopted
It is formed outside with the form of electrostatic spinning, other drug-carried coats can be any one using electrostatic spinning, spraying, extraction or brushing etc.
Kind of mode is formed, for example, other layers be all made of one of spraying, extraction, brushing, electrostatic spinning mode formed or every layer all
It is formed using different generation types or part drug-carried coat uses identical generation type part using different formation sides
Formula.But because the drug release for the medication coat that method of electrostatic spinning is formed is slow, and spray, extract, brushing etc. what modes were formed
The drug release of medication coat is rapid, therefore preferably uses electrostatic spinning and spraying, extraction, brushes one of three kinds or a variety of
The mode of combined use is formed so that the drug in medicine carrying membrane can part quick release, part slow release, both met vertical
The purpose being administered, and it is able to achieve the purpose of long-term sustained release administration.Preferably, the last layer drug-carried coat does not use electrostatic spinning
Mode is formed.One layer of signified drug-carried coat, means the ingredient of this layer of drug-carried coat and generation type complete one in the present invention
Sample, using identical generation type but ingredient difference cannot can be regarded as same layer, using identical ingredient but generation type not
It is same to can be regarded as same layer.When ingredient is identical with generation type, even if by multi-pass operation formed drug-carried coat that calculate
Make same layer, such as in order to meet film drugloading rate or thickness requirement, the coating formed by the way of multiple spraying-drying is calculated
Make the same layer drug-carried coat formed using spraying method.
In a certain specific embodiment of the present invention, medicine carrying membrane is by the way of electrostatic spinning-spraying or Static Spinning
The mode or electrostatic spinning-brushing mode or electrostatic spinning-spraying-extraction mode or Static Spinning of silk-extraction
The mode or electrostatic spinning-spraying-extraction-brushing mode or electrostatic spinning-spraying-Static Spinning of silk-extraction-spraying
The mode or electrostatic spinning-spraying-electrostatic spinning-spraying mode or electrostatic spinning-extraction-Static Spinning of silk-extraction
The various ways such as the mode of silk-extraction are formed.
In a certain specific embodiment of the present invention, two layers adjacent of drug-carried coat uses the two different formation sides a and b
Formula；The a generation type refers to that electrostatic spinning mode is formed, and b generation type refers to any in spraying, extraction or brushing
A kind of mode is formed.For example, medicine carrying membrane is by the way of electrostatic spinning-spraying or electrostatic spinning-spraying-electrostatic spinning-spray
The mode or electrostatic spinning-extraction-electrostatic spinning-extraction mode of painting or electrostatic spinning-spraying-electrostatic spinning-leaching
The various ways such as the mode mentioned are formed.
Preferably, the number of plies of drug-carried coat is 2 layers, and second layer drug-carried coat passes through any in spraying, extraction or brushing
A kind of mode is formed.Such as medicine carrying membrane by the way of electrostatic spinning-spraying perhaps electrostatic spinning-extraction mode or
Electrostatic spinning-brushing mode.
Further, the thickness of each layer drug-carried coat can be according to drugloading rate, the type and quantity of drug, requirement etc.
Different reasons are adjusted, and the thickness of every layer of drug-carried coat is about 0.05-0.2mm.
In a certain specific embodiment of the present invention, the surface of the medicine carrying membrane is preferably non-smooth structure, with increase with
Protrusion or/and groove is distributed in the frictional force of surrounding tissue, the surface of medicine carrying membrane, and protrusion or/and groove are preferably evenly distributed through
The shape of medicine carrying membrane surface, protrusion or/and groove can choose at random, and can be wavy, zigzag, helical form, needle-shaped, stick
At least one of shape, diagram shape etc., the diagram shape protrusion can be circle, ellipse, regular polygon, non-regular polygon,
At least one of irregular figure etc..Protrusion or/and the height or depth of groove can according to need and be adjusted, generally
0.01~0.1 mm.The vertebral plasty dilating sacculus that surface of the present invention carries medicine expands expansion under elevated pressure, then receives pressure and withdraws from body
It is interior, when balloon body becomes contraction state from expansion swelling state, medicine carrying membrane due to interpyramidal stress and friction masterpiece
It is separated with sacculus, maintains the shape of balloon body expanse, medicine carrying membrane, which can wrap, after further bone cement injection wraps bone
Cement plays the role of preventing its leakage, avoids damage to surrounding tissue, and the protrusion or/and groove on medicine carrying membrane surface can increase
The disengaging of frictional force between bone cement and centrum, more conducively medicine carrying membrane and balloon body, while being also possible to prevent its package
Bone cement abjection is in situ, and on the other hand protrusion or/and groove can increase the specific surface area of medicine carrying membrane, improves drugloading rate.
Further, the protrusion on medicine carrying membrane surface or/and groove are by the protrusion or/and groove structure on each layer drug-carried coat
At on the surface of at least one layer of drug-carried coat equipped with protrusion or/and groove, i.e. protrusion or/and groove can be set in each layer
On, it can also be only arranged on the drug-carried coat of part, the shape of protrusion or/and groove and be described above consistent.Preferably, first
Layer drug-carried coat surface is equipped with protrusion or/and groove, and the load capacity of subsequent drug-carried coat can be improved in the protrusion or/and groove,
Improve drugloading rate, and by adjusting protrusion or/and groove height or depth can make first layer drug-carried coat protrusion or/
With groove still in the outer surface of medicine carrying membrane protrusion or recess.Preferably, protrusion or/and groove are equipped in first time drug-carried coat
On the basis of, it can also be equipped with protrusion or/and groove on other drug-carried coats, further increase drugloading rate or frictional force.
Further, drug-carried coat or protrusion on medicine carrying membrane or/and groove can be using feasible in the prior art
Meaning technology is realized, such as etching, engraving, blowing, compacting, laser grooving technology etc..
In a certain specific embodiment of the present invention, the medicine carrying membrane, which is equipped with, can penetrate the logical of each layer drug-carried coat
Hole, the size of through-hole are grade.When in the cavity that bone cement injection medicine carrying membrane is formed, bone cement can be with before not solidifying
It is oozed out on a small quantity by the through-hole on medicine carrying membrane, is formed and be similar to convex structure, play the work as the protrusion on medicine carrying membrane
With.
Further, balloon body of the present invention is percutaneous vertbroplasty or Percutaneous kyplasty now
In the dilating sacculus that is commonly used, be referred to as balloon-expandable or expansiveness sacculus, can directly purchase from the market
It can buy, can also voluntarily be prepared according to method disclosed in the prior art.In general, dilating sacculus uses polyethylene (PE), gathers
One of materials such as ethylene glycol terephthalate (PET), polyamide (PA), nylon elastomer (Pebax), polyurethane (PU)
Or it a variety of is made.When pressurized, the balloon body expansion compresses surrounding tissue, bounces back after removing pressure, and forming one can inject
The cavity of bone cement.
Further, contain drug and degradable high polymer material, drug in the drug-carried coat formed by electrostatic spinning
It combines together after electrostatic spinning with degradable high polymer material, it is not easy to discharge, degrade in degradable high polymer material
Slow release in the process plays the role of sustained release.In the drug-carried coat formed by modes such as other sprayings, extraction or brushings
Degradable high polymer material is free of containing drug, drug can be with quick release.Electrostatic spinning, spraying, extraction are brushed and can be adopted
It is operated with the conventional steps reported in the prior art.
Further, one or more drugs can be contained in every layer of drug-carried coat, the drug in each layer drug-carried coat can
With identical, can also be different；Drugloading rate in every layer of drug-carried coat may be the same or different.The drug can be suppression
One of bone resorption drug processed, promoting bone growing drug, analgesic drug product, anaesthetic etc. are a variety of；The inhibition bone resorption
Drug includes diphosphonate, and the promoting bone growing drug includes parathyroid hormone, prostaglandin E2, fluoride, strontium salt etc.
At least one of, the analgesic drug product includes Aspirin-arginine, and the anaesthetic includes procaine, lidocaine
At least one of Deng.
Further, the degradable high polymer material is polylactic acid (PLA), poly lactide-glycolide acid
(PLGA), chitosan, sodium alginate, polyethylene glycol (PEG), polyglycolide (PGA), polycaprolactone (PCL), poly-aspartate
(PASP), in sodium carboxymethylcellulose (CMC), hydroxypropyl methyl cellulose (INN), polyvinyl alcohol (PVA), polyethers etc. at least
It is a kind of.The performance parameter requirement of degradable high polymer material are as follows: viscosity 0.1-0.5 dl/g, weight average molecular weight 20000-
100000.The selection of degradable high polymer material through the invention, not only can satisfy the requirement of electrostatic spinning fluid viscosity, but also can be with
Medicine carrying membrane is set to be more conducive to the disengaging with balloon body after balloon body expansion retraction, more conducively medicine film forms one and can accommodate
The cavity of bone cement.
Further, the drugloading rate for the drug-carried coat for using method of electrostatic spinning to be formed is 1~300 mg/cm2。
It uses spraying, extraction or brushes the drugloading rate of the drug-carried coat formed as 1~500 mg/cm2。
Further, the preparation method of the vertebral plasty dilating sacculus of medicine, the party are carried the present invention also provides a kind of surface
Method the following steps are included:
(1) drug, high molecular degradable material are made into electrostatic spinning liquid, progress electrostatic spinning is formed thin on balloon body surface
Film, it is dry after electrostatic spinning, obtain first layer drug-carried coat；
(2) drug solution of the electrostatic spinning liquid containing drug and high molecular degradable material or compounding pharmaceutical and solvent is prepared,
Selection electrostatic spinning, spraying, extraction or brushing mode form each layer drug-carried coat, finally obtain the vertebral plasty expansion that surface carries medicine
Open sacculus.
Further, in step (1), in the electrostatic spinning liquid other than drug, high molecular degradable material, also contain
Other compositions needed for electrostatic spinning, these ingredients can be selected according to disclosure in the prior art.Electrostatic spinning
Condition be adjusted according to thickness, the drugloading rate etc. of required film.
Further, in step (2), the solvent can be the solvent that arbitrarily can be used for human body, can dissolve drug, example
Preferentially selecting water such as water soluble drug is solvent, and water-insoluble medicine selects suitable solvent according to the property of different pharmaceutical, molten
Agent can be one kind, be also possible to a variety of.
It further, further include that protrusion or groove are formed at least one layer of drug-carried coat in above-mentioned preparation method
Step.
Further, in above-mentioned preparation method, further include the steps that forming through-hole on medicine carrying membrane.
The invention discloses the vertebral plasty dilating sacculus that a kind of surface carries medicine, including balloon body, in balloon body table
Has medicine carrying membrane in face.The vertebral plasty dilating sacculus that the surface carries medicine can be applied in the Minimally Invasive Surgeries such as kyphoplasty restore
Vertebral height forms and keeps bone cement filling cavity, and part discharges drug, reduces secondary fracture and second fracture, has following
The utility model has the advantages that
1, medicine carrying membrane is arranged on balloon body surface in the present invention, in balloon body pressurized expansion, loose centrum tissue due to
The case where pressure effect is extruded consolidation, alleviates local osteoporosis；Sacculus depressurize be detached from when, medicine carrying membrane due to and centrum
Between stress and friction power effect separated with sacculus, temporarily support centrum shape, be retained in affected part and contacted with centrum tissue tight,
Cavity and package are provided for the bone cement of filling, prevents from spilling over other tissues outside bone cement disperse, avoids causing nerve, dural sac
The severe complications such as damage.
2, medicine carrying membrane of the present invention is made of the drug-carried coat of multilayer, passes through the mode that is differently formed of drug-carried coat, medicine carrying membrane
Not only can be placed in it is internal when rapid delivery of pharmaceuticals, moreover it is possible to be retained in the sustained release of affected part longer time, obtain better drug
Utilization rate.
3, medicine carrying membrane of the present invention quickly and slowly locally can discharge drug, to reach inhibition bone resorption, promote bone shape
At or analgesic effect, can further alleviate bone-loss in repair process after surgery, improve bone density, obtain better
The postoperative effect of Osteoporotic vertebral fracture reduces the incidence of secondary fracture.
4, the contained drug of medicine carrying membrane of the present invention blood running can enter blood circulation under using in centrum, to realize that whole body is used
Medicine solves the problems, such as that oral medication stomach degree of being absorbed and utilized is low, improves utilization ratio of drug, and then increase in patient's unit volume
Bone tissue amount, mitigating osteoporosis disease.
5, the structures such as protrusion, recess, through-hole can be set on medicine carrying membrane of the present invention, on the one hand can increase bone cement and vertebra
Frictional force between body prevents bone cement abjection in situ, on the other hand increases the specific surface area of medicine carrying membrane, improves drugloading rate.
Detailed description of the invention
The surface of the present invention Fig. 1 carries the structural schematic diagram of the vertebral plasty dilating sacculus of medicine；Wherein, 1, surface carries the vertebra of medicine
Body forming expansion sacculus, 2, balloon body, 3, first layer drug-carried coat, 4, second layer drug-carried coat, 5 be foley's tube；
Surface carries the schematic diagram that uses of the vertebral plasty dilating sacculus of medicine in Fig. 2 Percutaneous kyplasty, left: before treatment,
Right: the vertebral plasty dilating sacculus pressurized expansion that surface carries medicine restores vertebral height；
The surface Fig. 3 carries the vertebral plasty dilating sacculus use state diagram of medicine, left: pressurized expansion；Right: decompression is withdrawn from；
Fig. 4 is retained in the schematic diagram of the bone cement of the medicine carrying membrane package filling in affected part；
The structural schematic diagram of the raised medicine carrying membrane of Fig. 5；Wherein, 1, the spiral protrusion axially extending along sacculus, 5, ball
Ductus bursae.
Fig. 6 has the schematic diagram of the medicine carrying membrane package bone cement of through-hole；Wherein, 1, the medicine carrying membrane with through-hole, 2, bone water
Mud passes through through-hole and forms protrusion.
Specific embodiment
Specific embodiments of the present invention are described in detail below, but embodiments of the present invention are not limited thereto.
In following embodiments, unless otherwise instructed, each raw material is commercially available from market.
Embodiment 1
A kind of surface carries the vertebral plasty dilating sacculus (abbreviation vertebral plasty dilating sacculus) of medicine, which carries the vertebral plasty of medicine
Dilating sacculus includes balloon body, has medicine carrying membrane on balloon body surface, the medicine carrying membrane is by least two layers of drug-carried coat
Composition, wherein directly contacting with balloon body is first layer drug-carried coat, other layer of drug-carried coat is in turn attached to one layer
Drug-carried coat on.Fig. 1 is the structural schematic diagram of the vertebral plasty dilating sacculus of 2 layers of drug-carried coat, including balloon body 2, the
One layer of drug-carried coat 3 and second layer drug-carried coat 4, first layer drug-carried coat 3 are directly contacted with balloon body 2, and the second layer carries medicine
Coating 4 is directly contacted with first layer drug-carried coat 3.
Further, the balloon body is dilating sacculus, is called balloon-expandable, expansiveness sacculus, abbreviation sacculus,
When balloon body becomes contraction state from expansion swelling state, most of medicine carrying membrane and balloon body are detached from.Balloon body can
Using any in the materials such as polyethylene, polyethylene terephthalate, nylon, Pebax, polyurethane, polyether-polyurethane
A kind of material is made.
Further, the drug-carried coat of first layer is formed by electrostatic spinning, and the drug-carried coat of other layers passes through Static Spinning
Silk, spraying, extraction or the mode brushed are formed.Preferably, by the medicine carrying membrane of electrostatic spinning formation with a thickness of 0.05-
0.2mm, such as 0.05mm, 0.1mm, 0.15mm, 0.2mm.Contain drug and can in the drug-carried coat formed by electrostatic spinning
Degraded macromolecular material containing drug but is free of degradable high polymer material in the drug-carried coat formed by other means.It is quiet
Electrospun, spraying, extraction or brushing are carried out using mode disclosed in the prior art.
Further, one or more drugs are contained in every layer of drug-carried coat, the drug in each layer drug-carried coat can phase
Together, it can also be different.The drug can be inhibition bone resorption drug, promoting bone growing drug, analgesic drug product, anaesthetic etc.
At least one of；The inhibition bone resorption drug includes diphosphonate, and the promoting bone growing drug includes parathyroid hormone
At least one of element, prostaglandin E2, fluoride, strontium salt etc., the analgesic drug product include Aspirin-arginine, the fiber crops
Liquor-saturated drug includes at least one of procaine, lidocaine etc..Using the load medicine for the drug-carried coat that method of electrostatic spinning is formed
Amount is 1~300 mg/cm2, this drugloading rate can be adjusted according to different drugs, different pharmaceutical requirements amounts, such as
1-20 mg/cm2、30-50 mg/cm2、60-90mg/cm2、100-200 mg/cm2、200-300 mg/cm2.Using spraying, leaching
The drugloading rate for mentioning or brushing the drug-carried coat formed is 1~500 mg/cm2, this drugloading rate can according to different drugs, no
Same pharmaceutical requirements amount is adjusted, such as 1-20 mg/cm2、30-50 mg/cm2、60-90mg/cm2、100-200 mg/
cm2、200-300 mg/cm2、300-400 mg/cm2、400-500 mg/cm2。
Further, the degradable high polymer material is polylactic acid (PLA), poly lactide-glycolide acid
(PLGA), chitosan, sodium alginate, polyethylene glycol (PEG), polyglycolide (PGA), polycaprolactone (PCL), poly-aspartate
(PASP), sodium carboxymethylcellulose (CMC), hydroxypropyl methyl cellulose (INN), polyvinyl alcohol (PVA), at least one in polyethers
Kind；The viscosity of degradable high polymer material is 0.1-0.5dl/g, weight average molecular weight 20000-100000.
Further, at least two layers of the number of plies of drug-carried coat, such as 2 layers, 3 layers, 4 layers, 5 layers, 6 layers, 7 layers etc., preferably
2-5 layers.The generation type or preparation method of two layers adjacent of drug-carried coat may be the same or different, such as other layers are equal
It is formed using one of spraying, extraction, brushing, electrostatic spinning mode or every layer is all formed using different generation types,
Or part drug-carried coat uses different generation types using identical generation type part.But because method of electrostatic spinning is formed
Medication coat drug release it is slow, and the drug release medication coat that modes are formed such as spray, extract, brushing is rapid,
Therefore it is preferably formed by the way of electrostatic spinning and one of spraying, extraction, three kinds of brushing or a variety of combined uses, with
Enable drug part quick release, the part slow release in medicine carrying membrane, not only meets the purpose being administered immediately, but also be able to achieve length
The purpose of phase sustained-release administration.Preferably, the last layer drug-carried coat does not use electrostatic spinning mode to be formed.
Preferably, two layers adjacent of drug-carried coat uses the two different generation types of a and b；What a generation type referred to
It is that electrostatic spinning mode is formed, b generation type refers to that any one mode in spraying, extraction or brushing is formed.For example, carrying
Medicine film is by the way of electrostatic spinning-spraying or electrostatic spinning-spraying-electrostatic spinning-spraying mode or Static Spinning
Silk-extraction-electrostatic spinning-extraction mode or electrostatic spinning-spraying-electrostatic spinning-extraction mode etc. are a variety of different
Mode is formed.
Preferably, the number of plies of the drug-carried coat is two layers, and second layer drug-carried coat passes through spraying, extraction or the side brushed
Formula is formed, for example, medicine carrying membrane formed by the way of electrostatic spinning-spraying perhaps electrostatic spinning-extraction mode formed or
Electrostatic spinning-brushing mode is formed.
Above-mentioned surface carry the usage mode of the vertebral plasty dilating sacculus of medicine as shown in Fig. 2, by surface carry the centrum of medicine at
The stretched casing of shape dilating sacculus is put into required position, as shown in figure 3, sacculus pressurization is made its expansion, restores vertebral height, so
Decompression is withdrawn from afterwards, as shown in figure 4, the medicine carrying membrane and sacculus of balloon surface are detached from after sacculus decompression is withdrawn from, are stayed in centrum and is formed
Cavity, the bone cement of package later period injection.
Embodiment 2
A kind of surface carries the vertebral plasty dilating sacculus (abbreviation vertebral plasty dilating sacculus) of medicine, with same as Example 1
Structure, further, the surface of medicine carrying membrane is non-smooth structure, and surface is distributed with protrusion or/and groove, protrusion or/
It is preferably evenly distributed through medicine carrying membrane surface with groove, raised or/and groove shape, which can be, can arbitrarily increase specific surface area
Or/and the shape of frictional force, such as wavy, zigzag, helical form, needle-shaped, rodlike, diagram shape etc., the figure can be
At least one of circle, ellipse, regular polygon, non-regular polygon, irregular figure etc..As shown in figure 3, medicine carrying membrane surface
It is evenly distributed with rodlike protrusion, as described in Figure 5, medicine carrying membrane surface is evenly distributed with spiral along axially extending convex of sacculus
It rises.
Further, the protrusion on medicine carrying membrane surface or/and groove by drug-carried coat protrusion or/and groove constitute,
At least the surface of first layer drug-carried coat is equipped with protrusion or/and groove, i.e., protrusion or/and groove can be set on each layer,
It can also be only arranged on the drug-carried coat of part, the shape of protrusion or/and groove and be described above consistent.
Further, it is described protrusion or/and groove using etching, engraving, blowing, compacting etc. modes formed, protrusion or/and
The height or depth of groove are 0.01 ~ 0.1 mm, such as 0.01mm, 0.02mm, 0.03mm, 0.05mm, 0.08mm, 0.1mm.
Preferably, first layer drug-carried coat surface is equipped with protrusion or/and groove, after the protrusion or/and groove can be improved
The load capacity of continuous drug-carried coat improves drugloading rate, and the height or depth by adjusting protrusion or/and groove can make first
The protrusion or/and groove of layer drug-carried coat are still in the outer surface of medicine carrying membrane protrusion or recess.It is furthermore preferred that carrying medicine in first time
Coating is equipped on the basis of protrusion or/and groove, and protrusion or/and groove can also be equipped on other drug-carried coats, is further increased
Load dose or frictional force.
Embodiment 3
A kind of surface carries the vertebral plasty dilating sacculus (abbreviation vertebral plasty dilating sacculus) of medicine, has and embodiment 1 or 2 phases
Same structure is further additionally provided with the through-hole that can penetrate each layer drug-carried coat on the medicine carrying membrane, the size of through-hole is milli
Meter level.As shown in fig. 6, bone cement can pass through load before not solidifying when in the cavity that bone cement injection medicine carrying membrane is formed
Through-hole in medicine film oozes out on a small quantity, is formed and is similar to convex structure, played the role of as the protrusion on medicine carrying membrane.
Embodiment 4
1, prepare FG1010 type dilating sacculus；
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
5, spraying production second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
6, dry again: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
7, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Embodiment 5
1, prepare FG1010 type dilating sacculus；
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, jagged raised design is carved out using a picosecond ultraviolet laser on first layer drug-carried coat surface, setting sawtooth is convex
Playing height is 0.05mm, and the spacing of zigzag fashion is 1mm；
5, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
6, spraying production second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
7, dry again: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
8, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Embodiment 6
1, prepare FG1010 type dilating sacculus；
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, micropore is carved out using a picosecond ultraviolet laser on first layer drug-carried coat surface, setting micro-pore diameter is 1mm, micropore
The spacing in the center of circle is 5mm；
5, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
6, spraying production second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
7, dry again: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
8, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Embodiment 7
1, prepare FG1010 type dilating sacculus,
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
5, spraying production second layer drug-carried coat: by lidocaine solution according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
6, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
7, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Embodiment 8
1, prepare FG1010 type dilating sacculus,
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
5, spraying prepares second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
6, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
7, it weighs 1.3g PLGA to mix with 1.5ml dimethylformamide, 1.5ml tetrahydrofuran, 0.1g Strontium Ranelate, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
8, electrostatic spinning makes third layer drug-carried coat: third layer drug-carried coat is made on second layer drug-carried coat surface, it will be upper
The mixed solution for stating step 7 is added in the syringe of electrospinning device, and electrospinning parameters are arranged are as follows: 0.12 ml/h of speed,
30 cm of distance, -0.14 kV of negative pressure, 0.67 kV of high pressure, gained drug-carried coat is with a thickness of 0.2mm；
9, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
10, the 4th layer of drug-carried coat of spraying production: by Strontium Ranelate solution according to 1cm2The effective medicine of 1 ~ 500mg of sacculus area
The dosage of object is sprayed at third layer drug-carried coat surface；
11, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
12, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Embodiment 9
1, prepare FG1010 type dilating sacculus；
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution be added electrospinning device syringe in, setting electrospinning parameters be 0.12 ml/h of speed, 30 cm of distance,
- 0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of 0.2mm；
4, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
5, spraying production second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
6, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
7, it weighs 1.3g PLGA to mix with 1.5ml dimethylformamide, 1.5ml tetrahydrofuran, 0.1g Strontium Ranelate, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
8, electrostatic spinning makes third layer drug-carried coat: third layer drug-carried coat is made on second layer drug-carried coat surface, it will be upper
The mixed solution for stating step 7 is added in the syringe of electrospinning device, and electrospinning parameters are arranged are as follows: 0.12 ml/h of speed,
30 cm of distance, -0.14 kV of negative pressure, 0.67 kV of high pressure, gained drug-carried coat is with a thickness of 0.2mm；
9, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
10, the 4th layer of drug-carried coat of spraying production: by Strontium Ranelate solution according to 1cm2The effective medicine of 1 ~ 500mg of sacculus area
The dosage of object is sprayed at third layer drug-carried coat surface；
11, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
12, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Embodiment 10
1, prepare FG1010 type dilating sacculus,
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
5, spraying production second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
6, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
7, it weighs 1.3g PLGA to mix with 1.5ml dimethylformamide, 1.5ml tetrahydrofuran, 0.1g calcitonin, magnetic under room temperature
Power stirs evenly, and obtains mixed solution；
8, electrostatic spinning makes third layer drug-carried coat: third layer drug-carried coat is made on second layer drug-carried coat surface, it will be upper
The mixed solution for stating step 7 is added in the syringe of electrospinning device, and electrospinning parameters are arranged are as follows: 0.12 ml/h of speed,
30 cm of distance, -0.14 kV of negative pressure, 0.67 kV of high pressure, gained drug-carried coat is with a thickness of 0.2mm；
9, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
10, the 4th layer of drug-carried coat of spraying production: by calcitonin solution according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at third layer carry medicine film surface；
11, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
12, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Two medicine carrying membrane sacculus layer by layer of the spiral protrusion axially extending along sacculus of embodiment 11
1, prepare FG1010 type dilating sacculus；
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, it is carved out on first layer drug-carried coat surface using picosecond ultraviolet laser spiral along axially extending convex of sacculus
Play pattern, height of projection 0.05mm, spacing 2mm；
5, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
6, spraying production second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
7, dry again: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
8, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made, which carries medicine
The structural schematic diagram of vertebral plasty dilating sacculus is as shown in figure 5, surface has the spiral protrusion axially extending along sacculus.
Embodiment 12
1, prepare FG1010 type dilating sacculus；
2, it weighs 1.3g PLGA, 1.5ml dimethylformamide, 1.5ml tetrahydrofuran and 0.1g diphosphonate to mix, under room temperature
Magnetic agitation is uniform, obtains mixed solution；
3, electrostatic spinning makes first layer drug-carried coat: it is grounded after the sacculus of foley's tube is filled with nominal pressure, it will be above-mentioned
Mixed solution is added in the syringe of electrospinning device, electrospinning parameters is arranged are as follows: 0.12 ml/h of speed, distance 30
Cm, -0.14 kV of negative pressure, 0.67 kV of high pressure form drug-carried coat in balloon surface using electrostatic spinning technique, with a thickness of
0.2mm；
4, cilium shape raised design is carved out using a picosecond ultraviolet laser on first layer drug-carried coat surface, cilium diameter is
0.01mm, spacing 0.05mm；
5, dry: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
6, spraying production second layer drug-carried coat: by bisphosphonate solutions according to 1cm2Sacculus area 1 ~ 500mg active drug
Dosage, be sprayed at first layer drug-carried coat surface；
7, dry again: baking oven is dried in vacuo 30min controlled at 50 ~ 80 DEG C；
8, the gas in sacculus is excluded, roll film is carried out, the vertebral plasty dilating sacculus that surface carries medicine is made.
Claims (15)
1. a kind of surface carries the vertebral plasty dilating sacculus of medicine, including balloon body, it is characterized in that: having on balloon body surface
Medicine carrying membrane, the medicine carrying membrane are made of at least two layers of drug-carried coat, wherein carry medicine with the first layer that balloon body directly contacts
Coating is formed by electrostatic spinning.
2. vertebral plasty dilating sacculus according to claim 1, it is characterized in that: in addition to first layer drug-carried coat, other layers
Drug-carried coat formed by way of electrostatic spinning, spraying, extraction or brushing.
3. vertebral plasty dilating sacculus according to claim 1 or 2, it is characterized in that: two layers adjacent of drug-carried coat uses a
With the two different generation types of b；The a generation type refers to that electrostatic spinning mode is formed, and b generation type refers to spraying
It applies, any one mode in extraction or brushing is formed.
4. vertebral plasty dilating sacculus according to claim 1,2 or 3, it is characterized in that: the number of plies of the drug-carried coat is
2-5 layers.
5. vertebral plasty dilating sacculus according to claim 1,2 or 4, it is characterized in that: the number of plies of the drug-carried coat is
Two layers, second layer drug-carried coat is formed by way of spraying, extraction or brushing.
6. vertebral plasty dilating sacculus according to any one of claims 1-5, it is characterized in that: being formed by electrostatic spinning
Drug-carried coat in contain drug and degradable high polymer material；Contain drug in the drug-carried coat formed by other means,
Without degradable high polymer material；Contain one or more drugs in every layer of drug-carried coat.
7. vertebral plasty dilating sacculus according to claim 6, it is characterized in that: the drug be inhibit bone resorption drug,
At least one of promoting bone growing drug, analgesic drug product, anaesthetic；Preferably, the inhibition bone resorption drug includes double
Phosphonate, the promoting bone growing drug include at least one in parathyroid hormone, prostaglandin E2, fluoride and strontium salt
Kind, the analgesic drug product includes Aspirin-arginine, the anaesthetic include in procaine and lidocaine at least
It is a kind of.
8. vertebral plasty dilating sacculus according to claim 6, it is characterized in that: the degradable high polymer material is poly- cream
Acid (PLA), poly lactide-glycolide acid (PLGA), chitosan, sodium alginate, polyethylene glycol (PEG), polyglycolide
(PGA), polycaprolactone (PCL), poly-aspartate (PASP), sodium carboxymethylcellulose (CMC), hydroxypropyl methyl cellulose
(INN), at least one of polyvinyl alcohol (PVA), polyethers；Preferably, the viscosity of the degradable high polymer material is 0.1-
0.5dl/g, weight average molecular weight 20000-100000.
9. vertebral plasty dilating sacculus according to claim 1 to 8, it is characterized in that: using method of electrostatic spinning shape
At drug-carried coat drugloading rate be 1~300 mg/cm2；Using spraying, extraction or the drugloading rate for brushing the drug-carried coat formed
For 1~500 mg/cm2。
10. vertebral plasty dilating sacculus according to claim 1 to 9, it is characterized in that: the surface of medicine carrying membrane is
Protrusion or/and groove is distributed in non-smooth structure, surface；
Preferably, protrusion or/and groove are evenly distributed on medicine carrying membrane surface；
Preferably, protrusion or/and the shape of groove be wavy, zigzag, helical form, in needle-shaped, rodlike and diagram shape extremely
Few one kind, the diagram shape protrusion are circle, ellipse, regular polygon, at least one in non-regular polygon and irregular figure
Kind；
Preferably, protrusion or/and the height or depth of groove are 0.01 ~ 0.1 mm.
11. vertebral plasty dilating sacculus according to claim 10, it is characterized in that: the surface of at least the first drug-carried coat is set
Have protrusion or/and a groove, the protrusion on medicine carrying membrane surface or/and groove by each layer drug-carried coat protrusion or/and groove constitute.
12. vertebral plasty dilating sacculus described in any one of -11 according to claim 1, it is characterized in that: being set on the medicine carrying membrane
There is the through-hole that can penetrate each layer drug-carried coat；Preferably, the size of through-hole is grade.
13. vertebral plasty dilating sacculus described in any one of -12 according to claim 1, it is characterized in that: each layer drug-carried coat
With a thickness of 0.05-0.2mm.
14. a kind of surface of any of claims 1 or 2 carries the preparation method of the vertebral plasty dilating sacculus of medicine, it is characterized in that:
(1) drug, high molecular degradable material are made into electrostatic spinning liquid, progress electrostatic spinning is formed thin on balloon body surface
Film, it is dry after electrostatic spinning, obtain first layer drug-carried coat；
(2) electrostatic spinning liquid containing drug and high molecular degradable material or compounding pharmaceutical are prepared and the drug of solvent is molten
Liquid, select electrostatic spinning, spraying, extraction or brush mode form each layer drug-carried coat, finally obtain surface carry medicine centrum at
Shape dilating sacculus.
15. preparation method according to claim 14, it is characterized in that: further including following a or/b step:
A. the step of forming protrusion or groove at least one layer of drug-carried coat；
B. the step of forming through-hole on medicine carrying membrane.
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| CN201910488081.7A CN110141760B (en) | 2019-06-05 | 2019-06-05 | Centrum forming expansion balloon with drug loaded on surface and preparation method thereof |
| PCT/CN2020/091478 WO2020244388A1 (en) | 2019-06-05 | 2020-05-21 | Surface-drug-loading inflatable balloon for vertebroplasty and preparation method therefor |
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| CN201910488081.7A CN110141760B (en) | 2019-06-05 | 2019-06-05 | Centrum forming expansion balloon with drug loaded on surface and preparation method thereof |
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| WO2020244388A1 (en) * | 2019-06-05 | 2020-12-10 | 山东百多安医疗器械股份有限公司 | Surface-drug-loading inflatable balloon for vertebroplasty and preparation method therefor |
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| CN110575607B (en) * | 2019-10-07 | 2023-11-28 | 江苏暖阳医疗器械有限公司 | Medicine saccule |
| GB2590692A (en) * | 2019-12-24 | 2021-07-07 | Corthotec Ltd | Composition for improved bone fracture healing |
| CN114053249A (en) * | 2020-08-10 | 2022-02-18 | 山东百多安医疗器械股份有限公司 | Degradable drug-loaded film capable of treating systemic osteoporosis and preparation process thereof |
| CN114053249B (en) * | 2020-08-10 | 2023-06-02 | 山东百多安医疗器械股份有限公司 | Degradable medicine carrying film capable of treating systemic osteoporosis and preparation process thereof |
| CN113144375A (en) * | 2021-04-16 | 2021-07-23 | 上海市胸科医院 | Anti-wall-sticking double-resistance nano hemodialysis catheter |
| CN113144376A (en) * | 2021-04-16 | 2021-07-23 | 上海市胸科医院 | Nano double-resistance deep venous catheter |
| CN113144376B (en) * | 2021-04-16 | 2024-03-29 | 上海市胸科医院 | Nanometer double-resistance deep vein catheter |
| CN113144375B (en) * | 2021-04-16 | 2024-04-02 | 上海市胸科医院 | Wall-sticking-preventing double-resistance nano hemodialysis catheter |
| CN113975593A (en) * | 2021-09-16 | 2022-01-28 | 上海市普陀区中心医院 | Kedalong medicine balloon and preparation method thereof |
| CN114533231A (en) * | 2022-04-27 | 2022-05-27 | 杭州锐健马斯汀医疗器材有限公司 | Balloon body and preparation method and application thereof |
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| CN110141760B (en) | 2021-10-08 |
| WO2020244388A1 (en) | 2020-12-10 |
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