CN110141760B - Centrum forming expansion balloon with drug loaded on surface and preparation method thereof - Google Patents

Centrum forming expansion balloon with drug loaded on surface and preparation method thereof Download PDF

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CN110141760B
CN110141760B CN201910488081.7A CN201910488081A CN110141760B CN 110141760 B CN110141760 B CN 110141760B CN 201910488081 A CN201910488081 A CN 201910488081A CN 110141760 B CN110141760 B CN 110141760B
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drug
loaded
balloon
coating
vertebroplasty
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CN110141760A (en
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张海军
孙钢
田振凡
侯文博
周超
尹玉霞
鲁手涛
刘光
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Shandong Branden Medical Devices Co Ltd
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Shandong Branden Medical Devices Co Ltd
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Priority to PCT/CN2020/091478 priority patent/WO2020244388A1/en
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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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Engineering & Computer Science (AREA)
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Abstract

The invention discloses a surface drug-loaded centrum shaping expansion balloon and a preparation method thereof. The balloon body is provided with the drug-loaded membrane on the surface, the drug-loaded membrane is composed of multiple layers of drug-loaded coatings, the drug-loaded membrane can be kept in the body after the balloon is withdrawn to form a shell for wrapping bone cement, so that the balloon not only has the function of effectively releasing the drug to a required part and improving the action efficiency of the drug, but also has the function of preventing the bone cement from separating from the position, has multiple functions, improves the postoperative effect of percutaneous vertebroplasty and percutaneous kyphoplasty, and is particularly suitable for treating osteoporosis and related compression fracture.

Description

Centrum forming expansion balloon with drug loaded on surface and preparation method thereof
Technical Field
The invention relates to an expansion balloon for vertebroplasty, in particular to a vertebroplasty expansion balloon with drug loaded on the surface and a preparation method thereof, belonging to the technical field of medical instruments for percutaneous vertebroplasty.
Background
With the aggravation of the aging phenomenon of the society, osteoporosis becomes a common disease which endangers the health of the elderly. The fracture healing process caused by osteoporosis is slow, the risk of secondary fracture is large, and the life quality of patients is obviously influenced. In 1984, french physicians first used Percutaneous Vertebroplasty (PVP), percutaneous injection of bone cement methyl methacrylate (PMMA) to increase spinal stability, relieve pain to the patient, and prevent further vertebral body collapse. Later, this technology was introduced into the united states, and based on this technology, Percutaneous Kyphoplasty (PKP) was developed, which uses an expansion balloon to expand inside the vertebral body to form a cavity filled with bone cement, thereby enhancing strength and stability of the vertebral body, reducing compression and stimulation to nerves, alleviating pain of patients, and improving the quality of life of patients after surgery.
However, percutaneous kyphoplasty has some disadvantages over many years. For example: the bone cement is easy to leak and disperse during injection, and can damage nerves, veins or other tissues; after being supported for a period of time, the bone cement is not tightly connected with the original vertebral body tissue and is easy to fall out of the original position; osteoporosis causes decreased bone density, loss of bone mass, and increased bone fragility, and is prone to secondary fractures and secondary fractures. The balloon used in percutaneous vertebroplasty or percutaneous kyphoplasty is made of polyethylene, polyethylene terephthalate, nylon elastomer (Pebax), polyurethane, polyether polyurethane and other materials, has a smooth surface, can only realize the function of forming a cavity by in vivo expansion, and cannot solve the defects.
In addition to percutaneous vertebroplasty, there are some disease treatment fields that require the use of a dilatation balloon, and most commonly, the interventional treatment field of coronary heart disease and other diseases. In the interventional treatment of coronary heart disease and other diseases, the need existsThe drug eluting balloon is used for acting in the blood vessel to play a role in reducing the stenosis of the blood vessel. For example, in 2004, SeQuent®The Please medicinal balloon is used for attaching iopromide and paclitaxel to the surface of the balloon for the first time and is applied to treatment of restenosis in a human body stent. Later Kang-Ju Lee et al in 2017 discovered that the utilization rate of the loaded drug can be improved by forming micro-textures on the surface of the drug balloon by adopting a blow molding process, so that the balloon and the blood vessel have larger contact area. Similarly, chinese patent CN107088259A discloses a balloon structure with a flap, which carries drug at 360 °, and the surface of the balloon in the flap can contact with the blood vessel when the balloon is full to release the drug. Patent CN108853690A discloses a design of a membrane-sealed drug-storing balloon, which directly presses the surface of the balloon out of surface texture, sprays drug on the surface, then uses a covering membrane to seal the balloon, and when the balloon is full in a blood vessel, the covering membrane is broken to release the drug.
The balloons are used in blood vessels and are designed according to the special use environment of the blood vessels, the surface of each balloon is loaded with drugs, but the drug delivery is realized by contacting the drug with the blood vessels, and the drug cannot be remained at an affected part for a long time to achieve the purpose of sustained release.
Chinese patent CN107596455A uses a degradable polymer mesh balloon to wrap bone cement, and adds nano ZnO to realize the antibacterial property of the material, and the defects of the patent are: the balloon can not expand and lift the vertebral body to form a bone cement perfusion cavity, and can not extrude and compact loose vertebral body tissues, so that the effect of restoring the height of the vertebral body is poor; moreover, the reticular balloon does not realize drug loading, so that the cause of osteoporosis cannot be treated, and the incidence rate of secondary fracture is high. Patent CN106726019A discloses a transforaminal nano bioglass coating minimally invasive fusion cage, which uses cobalt-chromium alloy wires to realize flexibility and mechanical support, attaches a nano bioglass coating on the surface to increase biocompatibility, and is applied to lumbar intervertebral fusion under an intervertebral foramen mirror to treat lumbar instability. The patent has different application fields, and does not realize the functions of forming the bone cement filling cavity and carrying the medicine.
Therefore, the presently disclosed balloons are single in function, and no balloon capable of achieving multiple functions of preventing bone cement dislocation, ensuring medicine continuous action, improving bone density, reducing fracture occurrence probability caused by osteoporosis and the like is disclosed.
Disclosure of Invention
Aiming at the defect of single effect of the balloon used in the existing percutaneous vertebroplasty or percutaneous kyphoplasty, the invention provides the vertebroplasty expanding balloon with drug loaded on the surface, the drug loaded membrane is attached to the surface of the expanding balloon, the drug loaded membrane can be kept in the body after the balloon is withdrawn to form a shell for wrapping bone cement, the balloon not only has the effect of effectively releasing the drug to the required part and improves the effect efficiency of the drug, but also has the effect of preventing the bone cement from being separated from the position, has multiple functions, improves the postoperative effect of the percutaneous vertebroplasty and the percutaneous kyphoplasty, and is particularly suitable for treating osteoporosis and related compression fracture.
The invention also provides a preparation method of the surface drug-loaded vertebroplasty dilatation balloon, which is simple to operate, easy to implement and convenient for industrial production.
The specific technical scheme of the invention is as follows:
the invention provides a surface drug-loaded vertebral body forming expansion balloon which comprises a balloon body, wherein a drug-loaded film is attached to the surface of the balloon body, the drug-loaded film is composed of at least two layers of drug-loaded coatings, and the first layer of drug-loaded coating which is directly contacted with the balloon body is formed through electrostatic spinning.
The medicine-carrying film is attached to the surface of the balloon body, the medicine-carrying film expands along with the balloon body when the balloon body is pressurized and expanded, when the balloon body is released and compressed and retracted, the medicine-carrying film is separated from the balloon due to the action of stress and friction between the medicine-carrying film and a vertebral body, the shape of the medicine-carrying film when the balloon body is expanded is still maintained, and the medicine-carrying film is kept at an affected part and is tightly contacted with vertebral body tissues, so that bone cement can be injected into a cavity wrapped by the medicine-carrying film, the medicine-carrying film is equivalent to a shell of the bone cement, and the bone cement is wrapped by the medicine-carrying film to prevent the bone cement from leaking.
Further, the number of the drug-loaded coating layers can be selected and adjusted according to the actual needs of the type and the drug-loaded amount of the required drugs, and the like, and the number of the drug-loaded coating layers is at least two, preferably 2 to 5, such as 2, 3, 4, and 5. Except that the first drug-carrying coating is formed in the form of electrostatic spinning, other drug-carrying coatings can be formed in any one of the forms of electrostatic spinning, spraying, leaching or brushing, for example, other layers are formed in one of the forms of spraying, leaching, brushing and electrostatic spinning, or each layer is formed in a different forming mode, or part of the drug-carrying coatings are formed in the same forming mode and part of the drug-carrying coatings are formed in different forming modes. However, because the drug release of the drug coating formed by the electrostatic spinning method is slow, and the drug release of the drug coating formed by the spraying, leaching, brushing and the like is rapid, the drug coating is preferably formed by one or more of the three modes of electrostatic spinning, spraying, leaching and brushing, so that the drug in the drug-loaded film can be partially and rapidly released and partially and slowly released, the purpose of immediate drug delivery is met, and the purpose of long-term sustained-release drug delivery can be realized. Preferably, the last drug-loaded coating is formed without electrospinning. The medicine-carrying coating layer is formed by coating a plurality of layers of medicine-carrying coating layers on a substrate, wherein the medicine-carrying coating layers are formed by coating a plurality of layers of medicine-carrying coating layers on the substrate, and the medicine-carrying coating layers are formed by coating a plurality of layers of medicine-carrying coating layers on the substrate. When the composition and the formation mode are the same, even if the drug-loaded coating is formed by a plurality of operations, the same layer is counted, for example, in order to meet the requirement of the drug-loaded amount or thickness of the film, the coating formed by a plurality of spraying-drying modes is counted as the same drug-loaded coating formed by a spraying mode.
In one embodiment of the present invention, the drug-loaded membrane is formed by a variety of different methods, such as electrospinning-spraying, electrospinning-leaching, electrospinning-brushing, electrospinning-spraying-leaching, electrospinning-leaching-spraying, electrospinning-spraying-leaching-brushing, electrospinning-spraying-electrospinning-leaching, electrospinning-spraying-electrospinning-electrostatic spinning-leaching, electrospinning-spraying-electrostatic spinning-leaching, or electrospinning-leaching-electrospinning-electrostatic spinning-leaching.
In a specific embodiment of the invention, two adjacent layers of drug-loaded coatings adopt two different forming modes of a and b; the formation mode of a refers to electrostatic spinning formation, and the formation mode of b refers to any one of spraying, leaching or brushing. For example, the drug-loaded membrane is formed by a plurality of different ways, such as an electrospinning-spraying way, or an electrospinning-spraying-electrospinning-spraying way, or an electrospinning-leaching-electrospinning-leaching way, or an electrospinning-spraying-electrospinning-leaching way.
Preferably, the number of the drug-loaded coating layers is 2, and the second drug-loaded coating layer is formed by any one of spraying, leaching or brushing. For example, the drug-loaded membrane adopts an electrostatic spinning-spraying mode, or an electrostatic spinning-leaching mode, or an electrostatic spinning-painting mode.
Furthermore, the thickness of each layer of medicine-carrying coating can be adjusted according to different reasons such as medicine-carrying amount, the type and the quantity of medicines, use requirements and the like, and the thickness of each layer of medicine-carrying coating is about 0.05-0.2 mm.
In a specific embodiment of the present invention, the surface of the drug-loaded membrane is preferably non-smooth structure to increase friction with surrounding tissues, the surface of the drug-loaded membrane is distributed with protrusions and/or grooves, the protrusions and/or grooves are preferably uniformly distributed on the surface of the drug-loaded membrane, the shape of the protrusions and/or grooves can be selected at will, and can be at least one of wave shape, saw tooth shape, spiral shape, needle shape, rod shape, figure shape, and the like, and the figure shape protrusions can be at least one of circle, ellipse, regular polygon, non-regular polygon, irregular figure, and the like. The height or depth of the protrusion or/and the groove can be adjusted according to the requirement, and is generally 0.01-0.1 mm. The expansion balloon for the vertebroplasty with drug loaded on the surface expands and expands under pressure, and then is withdrawn from the body after compression, when the balloon body is changed from the expansion and expansion state to the contraction state, the drug loaded membrane is separated from the balloon due to the stress and friction force between the drug loaded membrane and the centrum, so as to maintain the expansion and expansion shape of the balloon body, further, the drug loaded membrane can wrap bone cement after the bone cement is injected, so that the leakage of the bone cement is prevented, and surrounding tissues are prevented from being damaged, the friction force between the bone cement and the centrum can be increased by the bulges or/and the grooves on the surface of the drug loaded membrane, the drug loaded membrane is more favorable for being separated from the balloon body, the wrapped bone cement can be prevented from being separated from the original position, and on the other hand, the specific surface area of the drug loaded membrane can be increased, and the drug loading amount is increased.
Furthermore, the projections or/and grooves on the surface of the drug-loaded film are formed by the projections or/and grooves on each drug-loaded coating, the projections or/and grooves are arranged on the surface of at least one drug-loaded coating, namely, the projections or/and grooves can be arranged on each drug-loaded coating or only arranged on part of the drug-loaded coatings, and the shapes of the projections or/and grooves are consistent with the above description. Preferably, the surface of the first drug-loaded coating is provided with protrusions or/and grooves, the protrusions or/and grooves can improve the loading capacity of the subsequent drug-loaded coating and improve the drug loading capacity, and the protrusions or/and grooves of the first drug-loaded coating can still protrude or recess on the outer surface of the drug-loaded film by adjusting the height or depth of the protrusions or/and grooves. Preferably, on the basis that the first drug-loaded coating is provided with the protrusions or/and the grooves, the protrusions or/and the grooves can be arranged on other drug-loaded coatings, so that the drug-loaded amount or the friction force is further increased.
Further, the projections and/or grooves on the drug-loaded coating or film can be realized by any technique available in the prior art, such as etching, carving, blowing, pressing, laser grooving, and the like.
In a specific embodiment of the invention, the drug-loaded film is provided with through holes capable of penetrating through each layer of drug-loaded coating, and the size of the through holes is millimeter. When the bone cement is injected into the cavity formed by the drug-loaded membrane, the bone cement can slightly seep out through the through hole on the drug-loaded membrane before being solidified, so that a structure similar to a bulge is formed, and the effect similar to that of the bulge on the drug-loaded membrane is achieved.
Furthermore, the balloon body of the invention is a dilatation balloon commonly used in percutaneous vertebroplasty or percutaneous kyphoplasty, and can also be called as an inflatable balloon or an expandable balloon, and the balloon body can be directly purchased from the market and can also be prepared by the method disclosed in the prior art. Generally, the dilatation balloon is made of one or more of Polyethylene (PE), polyethylene terephthalate (PET), Polyamide (PA), nylon elastomer (Pebax), Polyurethane (PU), and the like. When the balloon body is pressurized, the balloon body can be expanded to compress surrounding tissues and retract after pressure is removed, so that a cavity capable of being injected with bone cement is formed.
Furthermore, the medicine-carrying coating formed by electrostatic spinning contains medicines and degradable high polymer materials, the medicines are fused with the degradable high polymer materials into a whole after electrostatic spinning, the medicines are not easy to release, and the medicines are slowly released in the degradation process of the degradable high polymer materials, so that the slow release effect is achieved. The drug-loaded coating formed by other spraying, leaching or brushing modes contains drugs and does not contain degradable high polymer materials, and the drugs can be quickly released. Electrospinning, spraying, leaching or brushing can be carried out using conventional procedures reported in the prior art.
Furthermore, each layer of the medicine-carrying coating can contain one or more medicines, and the medicines in each layer of the medicine-carrying coating can be the same or different; the drug loading amount in each drug-loaded coating layer can be the same or different. The medicine can be one or more of bone absorption inhibiting medicine, bone formation promoting medicine, pain relieving medicine, anesthetic medicine, etc.; the bone resorption inhibiting drug comprises bisphosphonate, the bone formation promoting drug comprises at least one of parathyroid hormone, prostaglandin E2, fluoride, strontium salt, etc., the analgesic drug comprises arginine aspirin, and the anesthetic drug comprises at least one of procaine, lidocaine, etc.
Further, the degradable polymer material is at least one of polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), chitosan, sodium alginate, polyethylene glycol (PEG), Polyglycolide (PGA), Polycaprolactone (PCL), Polyaspartic Acid (PASP), sodium carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (INN), polyvinyl alcohol (PVA), polyether and the like. The performance parameter requirements of the degradable high polymer material are as follows: viscosity of 0.1-0.5dl/g, weight average molecular weight of 20000-100000. By selecting the degradable high polymer material, the requirement of the viscosity of the electrostatic spinning solution can be met, the drug-loaded membrane can be separated from the balloon body more easily after the balloon body expands and retracts, and the drug-loaded membrane can form a cavity capable of containing bone cement.
Further, the drug-loading coating formed by the electrostatic spinning method has the drug-loading rate of 1-300 mg/cm2。
The drug-loading coating formed by spraying, leaching or brushing is 1-500 mg/cm in drug loading amount2。
Further, the invention also provides a preparation method of the vertebroplasty expansion balloon with drug loaded on the surface, which comprises the following steps:
(1) preparing a drug and a high-molecular degradable material into an electrostatic spinning solution, performing electrostatic spinning on the surface of the balloon body to form a film, and drying after electrostatic spinning to obtain a first drug-loaded coating;
(2) preparing electrostatic spinning solution containing a drug and a high-molecular degradable material or drug solution containing a drug and a solvent, and forming each layer of drug-loaded coating by selecting electrostatic spinning, spraying, leaching or brushing, thereby finally obtaining the centrum-shaped expansion balloon with drug-loaded surface.
Further, in the step (1), the electrospinning solution contains other components required for electrospinning in addition to the drug and the high-molecular degradable material, and the components can be selected according to the disclosure in the prior art. The conditions of electrostatic spinning are adjusted according to the thickness, drug loading and the like of the required film.
Further, in the step (2), the solvent may be any solvent that can be applied to human body and can dissolve the drug, for example, water is preferably used as the solvent for the water-soluble drug, and a suitable solvent is selected for the water-insoluble drug according to the properties of different drugs, and the solvent may be one or more.
Further, the preparation method also comprises a step of forming bulges or grooves on at least one layer of the medicine-carrying coating layer.
Further, the preparation method also comprises a step of forming a through hole on the medicine carrying film.
The invention discloses a centrum shaping expansion balloon with drug loaded on the surface, which comprises a balloon body, wherein a drug loaded film is attached to the surface of the balloon body. The surface drug-loaded vertebral body forming expansion balloon can be applied to the minimally invasive operations such as vertebral body kyphoplasty and the like to recover the height of the vertebral body, form and keep a bone cement perfusion cavity, locally release drugs, reduce secondary fracture and secondary fracture, and has the following beneficial effects:
1. according to the invention, the medicine-carrying membrane is arranged on the surface of the balloon body, when the balloon body is pressurized and expanded, the loosened vertebral body tissue is extruded and compacted under the action of pressure, so that the condition of local osteoporosis is relieved; when the sacculus decompression breaks away from, the medicine carrying membrane supports centrum shape temporarily owing to with the separation of sacculus with stress and frictional force effect between the centrum, keeps somewhere in affected part and centrum tissue in close contact with, provides cavity and parcel for the bone cement who fills, prevents that bone cement from diffusing to overflow other tissues, avoids causing serious complications such as nerve, dural sac damage.
2. The drug-loaded membrane is composed of a plurality of drug-loaded coatings, and through different forming modes of the drug-loaded coatings, the drug-loaded membrane not only can quickly release drugs when being placed in a body, but also can be left at an affected part for a longer time to be slowly released, so that a better drug utilization rate is obtained.
3. The drug-loaded membrane can quickly and slowly release drugs locally so as to achieve the effects of inhibiting bone resorption, promoting bone formation or relieving pain, further relieve bone loss and improve bone density in the postoperative repair process, obtain better postoperative effect of osteoporotic vertebral fracture and reduce the incidence rate of secondary fracture.
4. The medicine carried by the medicine carrying membrane can enter blood circulation under the operation of centrum blood, thereby realizing the whole body medication, solving the problem of low gastrointestinal absorption and utilization rate of orally taken medicine, improving the utilization rate of the medicine, further increasing the bone tissue amount in unit volume of patients and lightening osteoporosis.
5. The drug-loaded membrane can be provided with structures such as bulges, depressions, through holes and the like, so that the friction force between bone cement and a vertebral body can be increased, the bone cement is prevented from being out of the original position, the specific surface area of the drug-loaded membrane is increased, and the drug-loaded capacity is improved.
Drawings
FIG. 1 is a schematic structural view of a surface drug-loaded vertebroplasty dilatation balloon of the present invention; the surface drug-loaded centrum forming expansion balloon comprises 1, 2, a balloon body, 3, a first drug-loaded coating, 4 and a second drug-loaded coating, and 5 is a balloon catheter;
fig. 2 is a schematic diagram of the use of a surface drug-loaded vertebroplasty dilatation balloon in percutaneous kyphoplasty, left: before treatment, right: the surface drug-loaded vertebral body forming expansion balloon is pressurized and expanded to restore the height of the vertebral body;
fig. 3 is a schematic view of the use state of the surface drug-loaded vertebroplasty dilatation balloon, left: pressurizing and expanding; and (3) right: decompressing and withdrawing;
FIG. 4 is a schematic view of bone cement filled in a drug-loaded membrane remaining on an affected part;
FIG. 5 is a schematic structural view of a drug-loaded membrane with protrusions; wherein, 1, spiral bulge extending along the axial direction of the saccule, 5, the saccule conduit.
FIG. 6 is a schematic view of a drug-loaded membrane with through holes wrapped around bone cement; wherein, 1, the medicine carrying membrane with a through hole, 2, the bone cement passes through the through hole to form a bulge.
Detailed Description
Specific examples of the present invention will be described in detail below, but the examples of the present invention are not limited thereto.
In the following examples, each raw material was purchased from the market unless otherwise specified.
Example 1
The utility model provides a surface medicine carrying's vertebroplasty expands sacculus (be referred to as the vertebroplasty expands sacculus for short), this surface medicine carrying's vertebroplasty expands sacculus includes the sacculus body, has medicine carrying membrane on sacculus body surface, medicine carrying membrane comprises at least two-layer medicine carrying coating, wherein, with sacculus body direct contact be first layer medicine carrying coating, other layer medicine carrying coating is attached to on the medicine carrying coating of last layer in proper order. Fig. 1 is a schematic structure diagram of a vertebroplasty expansion balloon with 2 layers of drug-loaded coatings, which comprises a balloon body 2, a first layer of drug-loaded coating 3 and a second layer of drug-loaded coating 4, wherein the first layer of drug-loaded coating 3 is directly contacted with the balloon body 2, and the second layer of drug-loaded coating 4 is directly contacted with the first layer of drug-loaded coating 3.
Furthermore, the balloon body is an expansion balloon, also called an expandable balloon or an expandable balloon, or simply a balloon, and when the balloon body is changed from an expansion state to a contraction state, most of the drug-loaded film is separated from the balloon body. The balloon body can be made of any one of polyethylene, polyethylene terephthalate, nylon, Pebax, polyurethane, polyether polyurethane and the like.
Further, the drug-loaded coating of the first layer is formed by electrostatic spinning, and the drug-loaded coatings of the other layers are formed by electrostatic spinning, spraying, leaching or brushing. Preferably, the thickness of the drug-loaded film formed by electrospinning is 0.05 to 0.2mm, e.g., 0.05mm, 0.1mm, 0.15mm, 0.2 mm. The drug-loaded coating formed through electrostatic spinning contains drugs and degradable high polymer materials, and the drug-loaded coating formed through other modes contains drugs but does not contain the degradable high polymer materials. Electrostatic spinning, spraying, leaching or brushing is carried out in the manner disclosed in the prior art.
Furthermore, each drug-carrying coating contains one or more drugs, and the drugs in each drug-carrying coating can be the same or different. The drug may be at least one of a bone resorption inhibiting drug, a bone formation promoting drug, an analgesic drug, an anesthetic drug, and the like; the bone resorption inhibiting drug comprises bisphosphonate, the bone formation promoting drug comprises at least one of parathyroid hormone, prostaglandin E2, fluoride, strontium salt, etc., the analgesic drug comprises arginine aspirin, and the anesthetic drug comprises at least one of procaine, lidocaine, etc. The drug-loading coating formed by the electrostatic spinning method has the drug-loading rate of 1-300 mg/cm2The drug loading can be adjusted according to different drugs and different drug requirements, such as 1-20 mg/cm2、30-50 mg/cm2、60-90mg/cm2、100-200 mg/cm2、200-300 mg/cm2. By spraying, leaching, or brushingThe drug loading of the drug coating is 1-500 mg/cm2The drug loading can be adjusted according to different drugs and different drug requirements, 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 at least one of polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), chitosan, sodium alginate, polyethylene glycol (PEG), Polyglycolide (PGA), Polycaprolactone (PCL), Polyaspartic Acid (PASP), sodium carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (INN), polyvinyl alcohol (PVA) and polyether; the viscosity of the degradable polymer material is 0.1-0.5dl/g, and the weight-average molecular weight is 20000-100000.
Further, the number of the drug-loaded coating layers is at least two, for example, 2, 3, 4, 5, 6, 7, etc., preferably 2 to 5. The adjacent two drug-loaded coatings can be formed in the same or different manners, for example, other layers are formed by one of spraying, leaching, brushing and electrostatic spinning, or each layer is formed in a different forming manner, or part of the drug-loaded coatings are formed in the same forming manner and part of the drug-loaded coatings are formed in different forming manners. However, because the drug release of the drug coating formed by the electrostatic spinning method is slow, and the drug release of the drug coating formed by the spraying, leaching, brushing and the like is rapid, the drug coating is preferably formed by one or more of the three modes of electrostatic spinning, spraying, leaching and brushing, so that the drug in the drug-loaded film can be partially and rapidly released and partially and slowly released, the purpose of immediate drug delivery is met, and the purpose of long-term sustained-release drug delivery can be realized. Preferably, the last drug-loaded coating is formed without electrospinning.
Preferably, two adjacent layers of drug-loaded coatings adopt two different forming modes of a and b; the formation mode of a refers to electrostatic spinning formation, and the formation mode of b refers to any one of spraying, leaching or brushing. For example, the drug-loaded membrane is formed by a plurality of different ways, such as an electrospinning-spraying way, or an electrospinning-spraying-electrospinning-spraying way, or an electrospinning-leaching-electrospinning-leaching way, or an electrospinning-spraying-electrospinning-leaching way.
Preferably, the number of the drug-loaded coating layers is two, and the second drug-loaded coating layer is formed by spraying, leaching or brushing, for example, the drug-loaded membrane is formed by electrostatic spinning-spraying, or electrostatic spinning-leaching, or electrostatic spinning-brushing.
The usage of the surface drug-loaded vertebral body forming expansion balloon is shown in figure 2, the surface drug-loaded vertebral body forming expansion balloon is placed into a required position through an expansion sleeve, the balloon is pressurized to expand to recover the height of a vertebral body as shown in figure 3, then the balloon is decompressed and withdrawn, and after the balloon is decompressed and withdrawn as shown in figure 4, a drug-loaded film on the surface of the balloon is separated from the balloon, is left in the vertebral body to form a cavity, and wraps bone cement injected at the later stage.
Example 2
The utility model provides a surface medicine carrying vertebroplasty expansion balloon (shortly called vertebroplasty expansion balloon), which has the same structure as in example 1, further, the surface of medicine carrying membrane is non-smooth structure, and its surface distributes and has the arch or/and recess, and the arch or/and recess preferably evenly distributes on medicine carrying membrane surface, and the shape of arch or/and recess can be arbitrary can increase specific surface area or/and frictional force the shape, for example wave form, cockscomb structure, heliciform, acicular, bar-like, figure form etc. the figure can be at least one in circular, oval, regular polygon, non-regular polygon, irregular figure etc.. As shown in figure 3, the medicine carrying membrane has rod-shaped protrusions uniformly distributed on its surface, and as shown in figure 5, the medicine carrying membrane has spiral protrusions uniformly distributed on its surface extending along the axial direction of the balloon.
Furthermore, the projections or/and grooves on the surface of the drug-loaded film are formed by the projections or/and grooves on the drug-loaded coating, the projections or/and grooves are arranged on the surface of at least the first drug-loaded coating, namely, the projections or/and grooves can be arranged on each layer or only on part of the drug-loaded coating, and the shapes of the projections or/and grooves are consistent with the above description.
Furthermore, the protrusions or/and the grooves are formed by etching, carving, blowing, pressing and the like, and the height or the depth of the protrusions or/and the grooves is 0.01-0.1 mm, such as 0.01mm, 0.02mm, 0.03mm, 0.05mm, 0.08mm and 0.1 mm.
Preferably, the surface of the first drug-loaded coating is provided with protrusions or/and grooves, the protrusions or/and grooves can improve the loading capacity of the subsequent drug-loaded coating and improve the drug loading capacity, and the protrusions or/and grooves of the first drug-loaded coating can still protrude or recess on the outer surface of the drug-loaded film by adjusting the height or depth of the protrusions or/and grooves. More preferably, on the basis that the first drug-loaded coating is provided with the protrusions or/and the grooves, the other drug-loaded coatings can also be provided with the protrusions or/and the grooves, so that the drug-loaded amount or the friction force is further increased.
Example 3
The utility model provides a vertebroplasty expansion balloon of surface medicine carrying (vertebral body shaping expansion balloon for short), it has the same structure with embodiment 1 or 2, and is further, still be equipped with the through-hole that can pierce through each layer medicine carrying coating on the medicine carrying membrane, the size of through-hole is the millimeter level. As shown in figure 6, when the bone cement is injected into the cavity formed by the drug-loaded membrane, the bone cement can slightly seep out through the through holes on the drug-loaded membrane before being solidified, so that a structure similar to a bulge is formed, and the bone cement has the same function as the bulge on the drug-loaded membrane.
Example 4
1. Preparing an FG1010 type expansion balloon;
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
5. and (3) spraying and manufacturing a second layer of drug-loaded coating: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
6. and (3) drying again: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
7. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.
Example 5
1. Preparing an FG1010 type expansion balloon;
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. a picosecond ultraviolet laser is used for carving a sawtooth-shaped protrusion pattern on the surface of the first drug-loaded coating, the height of the sawtooth protrusion is set to be 0.05mm, and the space between sawtooth shapes is 1 mm;
5. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
6. and (3) spraying and manufacturing a second layer of drug-loaded coating: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
7. and (3) drying again: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
8. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.
Example 6
1. Preparing an FG1010 type expansion balloon;
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. carving micropores on the surface of the first drug-loaded coating by using a picosecond ultraviolet laser, wherein the diameter of each micropore is 1mm, and the distance between the centers of the micropores is 5 mm;
5. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
6. and (3) spraying and manufacturing a second layer of drug-loaded coating: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
7. and (3) drying again: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
8. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.
Example 7
1. An FG1010 type dilatation balloon was prepared,
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
5. and (3) spraying and manufacturing a second layer of drug-loaded coating: mixing lidocaine solution at a ratio of 1cm2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
6. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
7. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.
Example 8
1. An FG1010 type dilatation balloon was prepared,
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
5. preparing a second drug-loaded coating by spraying: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
6. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
7. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of strontium ranelate, mixing, and magnetically stirring uniformly at normal temperature to obtain a mixed solution;
8. preparing a third drug-loaded coating by electrostatic spinning: preparing a third drug-loaded coating on the surface of the second drug-loaded coating, adding the mixed solution obtained in the step 7 into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high pressure is 0.67 kV, and the thickness of the obtained medicine-carrying coating is 0.2 mm;
9. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
10. and (3) spraying and manufacturing a fourth layer of drug-loaded coating: strontium ranelate solution is prepared according to 1cm2Spraying the balloon with the dosage of 1-500 mg of effective drug on the surface of the third drug-loaded coating;
11. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
12. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.
Example 9
1. Preparing an FG1010 type expansion balloon;
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: filling a balloon of the balloon catheter with nominal pressure, then grounding, adding the mixed solution into an injector of electrostatic spinning equipment, setting electrostatic spinning parameters to be 0.12 ml/h, 30 cm, negative pressure of-0.14 kV and high pressure of 0.67 kV, and forming a drug-loaded coating on the surface of the balloon by using an electrostatic spinning technology, wherein the thickness of the drug-loaded coating is 0.2 mm;
4. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
5. and (3) spraying and manufacturing a second layer of drug-loaded coating: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
6. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
7. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of strontium ranelate, mixing, and magnetically stirring uniformly at normal temperature to obtain a mixed solution;
8. preparing a third drug-loaded coating by electrostatic spinning: preparing a third drug-loaded coating on the surface of the second drug-loaded coating, adding the mixed solution obtained in the step 7 into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high pressure is 0.67 kV, and the thickness of the obtained medicine-carrying coating is 0.2 mm;
9. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
10. and (3) spraying and manufacturing a fourth layer of drug-loaded coating: strontium ranelate solution is prepared according to 1cm2Spraying the balloon with the dosage of 1-500 mg of effective drug on the surface of the third drug-loaded coating;
11. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
12. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.
Example 10
1. An FG1010 type dilatation balloon was prepared,
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
5. and (3) spraying and manufacturing a second layer of drug-loaded coating: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
6. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
7. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of calcitonin, and uniformly mixing the PLGA, the dimethylformamide, the tetrahydrofuran and the calcitonin at normal temperature by magnetic stirring to obtain a mixed solution;
8. preparing a third drug-loaded coating by electrostatic spinning: preparing a third drug-loaded coating on the surface of the second drug-loaded coating, adding the mixed solution obtained in the step 7 into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high pressure is 0.67 kV, and the thickness of the obtained medicine-carrying coating is 0.2 mm;
9. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
10. and (3) spraying and manufacturing a fourth layer of drug-loaded coating: adding calcitonin solution to the ratio of 1cm2Spraying the effective drug with the balloon area of 1-500 mg on the surface of the third drug-loaded film;
11. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
12. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.
EXAMPLE 11 spiral, balloon-axially extending, raised two-layered drug-loaded membrane balloon
1. Preparing an FG1010 type expansion balloon;
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. a picosecond ultraviolet laser is used for engraving a spiral convex pattern extending along the axial direction of the balloon on the surface of the first drug-loaded coating, the height of the convex pattern is 0.05mm, and the distance between the convex patterns is 2 mm;
5. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
6. and (3) spraying and manufacturing a second layer of drug-loaded coating: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
7. and (3) drying again: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
8. and removing gas in the balloon, and rolling to obtain the surface drug-loaded vertebroplasty expanding balloon, wherein the structural schematic diagram of the surface drug-loaded vertebroplasty expanding balloon is shown in fig. 5, and the surface of the surface drug-loaded vertebroplasty expanding balloon is provided with spiral bulges extending along the axial direction of the balloon.
Example 12
1. Preparing an FG1010 type expansion balloon;
2. weighing 1.3g of PLGA, 1.5ml of dimethylformamide, 1.5ml of tetrahydrofuran and 0.1g of bisphosphonate, and mixing the components uniformly under magnetic stirring at normal temperature to obtain a mixed solution;
3. preparing a first drug-loaded coating by electrostatic spinning: grounding the balloon of the balloon catheter after being inflated with nominal pressure, adding the mixed solution into an injector of electrostatic spinning equipment, and setting electrostatic spinning parameters as follows: the speed is 0.12 ml/h, the distance is 30 cm, the negative pressure is-0.14 kV, the high voltage is 0.67 kV, a drug-loaded coating is formed on the surface of the balloon by using an electrostatic spinning technology, and the thickness is 0.2 mm;
4. a picosecond ultraviolet laser is used for carving fiber hair-shaped convex patterns on the surface of the first layer of the drug-loaded coating, the diameter of cilia is 0.01mm, and the distance between cilia is 0.05 mm;
5. and (3) drying: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
6. and (3) spraying and manufacturing a second layer of drug-loaded coating: 1cm of bisphosphonate solution is added2Spraying the balloon with the effective drug dosage of 1-500 mg in area on the surface of the first drug-loaded coating;
7. and (3) drying again: controlling the temperature of the oven to be 50-80 ℃, and carrying out vacuum drying for 30 min;
8. removing gas in the balloon, and rolling to obtain the centrum forming expansion balloon with drug loaded on the surface.

Claims (16)

1. The utility model provides a vertebroplasty expansion balloon with drug loaded on the surface, which comprises a balloon body and is characterized in that: the surface of the balloon body is attached with a drug-loaded film, the drug-loaded film consists of at least two drug-loaded coatings, wherein the first drug-loaded coating which is directly contacted with the balloon body is formed by electrostatic spinning; two adjacent layers of drug-loaded coatings adopt two different forming modes of a and b; the formation mode of a refers to electrostatic spinning, and the formation mode of b refers to any one of spraying, leaching or brushing;
the drug-loaded coating formed by electrostatic spinning contains drugs and degradable high polymer materials; the drug-loaded coating formed by other methods contains drugs and does not contain degradable high polymer materials;
the degradable high polymer material is at least one of polylactic acid, polylactic acid-glycolic acid copolymer, chitosan, sodium alginate, polyethylene glycol, polyglycolide, polycaprolactone, polyaspartic acid, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, polyvinyl alcohol and polyether, the viscosity of the degradable high polymer material is 0.1-0.5dl/g, and the weight-average molecular weight is 20000-100000;
the surface of the drug-loaded membrane is of a non-smooth structure, and bulges or/and grooves are distributed on the surface of the drug-loaded membrane.
2. The vertebroplasty dilation balloon of claim 1, wherein: the number of the drug-loaded coating layers is 2-5.
3. The vertebroplasty dilation balloon of claim 1, wherein: the number of layers of the drug-loaded coating is two, and the second drug-loaded coating is formed by spraying, leaching or brushing.
4. The vertebroplasty dilation balloon of any of claims 1-3, wherein: each drug-loaded coating contains one or more drugs.
5. The vertebroplasty dilation balloon of claim 4, wherein: the medicine is at least one of bone absorption inhibiting medicine, bone formation promoting medicine, pain relieving medicine and anesthetic medicine.
6. The vertebroplasty dilation balloon of claim 5, wherein: the bone resorption inhibiting drug comprises a bisphosphonate, the bone formation promoting drug comprises at least one of parathyroid hormone, prostaglandin E2, fluoride and a strontium salt, the analgesic drug comprises arginine aspirin, and the anesthetic drug comprises at least one of procaine and lidocaine.
7. The vertebroplasty dilation balloon of any of claims 1-3, wherein: the drug-loading coating formed by the electrostatic spinning method has the drug-loading rate of 1-300 mg/cm2(ii) a The drug-loading coating formed by spraying, leaching or brushing is 1-500 mg/cm in drug loading amount2。
8. The vertebroplasty dilation balloon of claim 1, wherein: the bulges or/and the grooves are uniformly distributed on the surface of the drug-loaded membrane.
9. The vertebroplasty dilation balloon of claim 1, wherein: the shape of the protrusions or/and the grooves is at least one of a wave shape, a saw-tooth shape, a spiral shape, a needle shape, a rod shape, and a figure shape, and the figure shape protrusions are at least one of a circle shape, an oval shape, a regular polygon shape, a non-regular polygon shape, and an irregular figure.
10. The vertebroplasty dilation balloon of claim 1, wherein: the height or depth of the protrusion or/and the groove is 0.01-0.1 mm.
11. The vertebroplasty dilation balloon of claim 1, wherein: at least the surface of the first medicine carrying coating is provided with a bulge or/and a groove, and the bulge or/and the groove on the surface of the medicine carrying film is formed by the bulge or/and the groove on each medicine carrying coating.
12. The vertebroplasty dilation balloon of any of claims 1-3, wherein: the drug-loaded membrane is provided with a through hole which can penetrate through each layer of drug-loaded coating.
13. The vertebroplasty dilation balloon of claim 12, wherein: the size of the through-hole is in the millimeter level.
14. The vertebroplasty dilation balloon of any of claims 1-3, wherein: the thickness of each layer of the drug-loaded coating is 0.05-0.2 mm.
15. A method of preparing the surface drug-loaded vertebroplasty dilatation balloon of claim 1 or 2, which is characterized in that:
(1) preparing a drug and a high-molecular degradable material into an electrostatic spinning solution, performing electrostatic spinning on the surface of the balloon body to form a film, and drying after electrostatic spinning to obtain a first drug-loaded coating;
(2) preparing electrostatic spinning solution containing a drug and a high-molecular degradable material or preparing drug solution of the drug and a solvent, and forming each layer of drug-loaded coating by selecting electrostatic spinning, spraying, leaching or brushing, thereby finally obtaining the centrum-shaped expansion balloon with drug-loaded surface.
16. The method of claim 15, wherein: also comprises the following steps c or d:
c. forming projections or grooves on at least one layer of the drug-loaded coating;
d. and forming a through hole on the drug-loaded film.
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CN110141760B (en) * 2019-06-05 2021-10-08 山东百多安医疗器械股份有限公司 Centrum forming expansion balloon with drug loaded on surface and preparation method thereof
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