CN114748701A - Drug coating, drug balloon, preparation method and application of drug balloon - Google Patents

Drug coating, drug balloon, preparation method and application of drug balloon Download PDF

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Publication number
CN114748701A
CN114748701A CN202210288855.3A CN202210288855A CN114748701A CN 114748701 A CN114748701 A CN 114748701A CN 202210288855 A CN202210288855 A CN 202210288855A CN 114748701 A CN114748701 A CN 114748701A
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drug
balloon
coating
carrier
compound
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CN114748701B (en
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马翠杰
赵丽晓
刘扬扬
何智浩
王哲
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Lepu Medical Technology Beijing Co Ltd
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Lepu Medical Technology Beijing Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/06—Coatings containing a mixture of two or more compounds

Abstract

The invention provides a drug coating, a drug balloon, a preparation method and application of the drug balloon. The drug coating for the drug balloon comprises a drug and a carrier, wherein the carrier is a phenolic compound or a pyrone compound, and the mass ratio of the drug to the carrier is 1 (0.01-10). The drug balloon is obtained by coating the drug coating on the surface of the balloon. The invention takes the phenolic compound or the pyrone compound as a new carrier, improves the carrier selection efficiency of the drug coating, can obtain an ideal crystal form, obviously improves the quality of the drug coating, and prolongs the retention time of the drug when treating the stenosis disease of the blood vessel or other lumens, thereby leading the drug balloon catheter to better inhibit the restenosis of the lumens when treating the stenosis of the blood vessel, the urethra or the ureter.

Description

Drug coating, drug balloon, preparation method and application of drug balloon
Technical Field
The invention relates to the technical field of medicine balloons, in particular to a medicine coating, a medicine balloon, a preparation method and application of the medicine balloon.
Background
The medicine sacculus catheter is one kind of interventional medical equipment comprising catheter and medicine sacculus. The drug balloon consists of a balloon and a drug coating coated on the surface of the balloon. The drug balloon catheter is mainly used for expanding the stenotic part of the blood vessel, and releases drugs to the intima of the blood vessel while expanding the blood vessel, thereby playing a role in inhibiting the restenosis of the blood vessel.
The drug coating is generally prepared by dissolving a drug and a carrier in a solvent and coating the solution on the surface of the balloon to obtain the drug balloon. At present, in the technology at home and abroad, the carriers used for obtaining the drug balloon are generally contrast media, ester compounds, heparin, castor oil or hydrophilic dyes, sugar and sugar derivatives, polymers and the like, and the drugs are generally paclitaxel, rapamycin and the like. In conclusion, the drug coating formula is selected more, but most of the drug coatings obtained by the current formula are difficult to control the crystallization state of the drug coatings, and the retention time of the drug in the treatment of vascular or other luminal stenosis diseases is difficult to guarantee.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to overcome the defects that most of drug coatings obtained by the formula in the prior art are difficult to control the crystallization state of the drug coatings and to ensure the retention time of the drug balloon in the treatment of vascular or other luminal stenosis diseases.
Therefore, the invention provides a drug coating, which comprises a drug and a carrier, wherein the carrier is a phenolic compound or a pyrone compound, and the mass ratio of the drug to the carrier is 1 (0.01-10).
Further, the phenolic compound is selected from at least one of eugenol, thymol, grape polyphenol, tea polyphenol and thymol; the pyrone compound is at least one of maltol, ethyl maltol, coumarin, tartaric acid, flavone and flavonoid compounds;
Optionally, the carrier is preferably one or more of eugenol, tea polyphenol, thymol, maltol, ethyl maltol and tartaric acid.
Further, the drug is selected from at least one of paclitaxel, rapamycin, paclitaxel derivatives, and rapamycin derivatives.
The invention provides a drug balloon which is obtained by coating the drug coating on the surface of the balloon.
The invention provides a preparation method of a medicine balloon, which is the medicine balloon and comprises the following steps:
dissolving a drug and a carrier into a solvent to obtain a solution;
the solution is applied to the balloon surface to form a drug coating.
Further, the solvent is at least one selected from water, alcohol compounds, aliphatic hydrocarbon compounds, ether compounds, halogenated hydrocarbon compounds, ketone compounds, tetrahydrofuran and acetonitrile; the aliphatic hydrocarbon compound comprises n-hexane and/or n-butane; the ether compound comprises diethyl ether and/or propylene oxide; the halogenated hydrocarbon compound comprises chloroform; the ketone compound comprises acetone and/or methyl butanone.
Furthermore, the mass ratio of the medicine to the solvent is 1 (0.002-50).
Further, the alcohol compound is a compound with the carbon number less than or equal to 15; the alcohol compound is at least one selected from ethanol, methanol, isopropanol, propanol, n-butanol, isobutanol and sec-butanol.
Further, in the dissolving step, after the drug and the carrier are added into the solvent, stirring, ultrasonic oscillation and standing are performed.
Further, the standing time is 0.5-1.5 h.
Further, the coating means includes spray coating, dip coating or drop coating.
The medicine balloon prepared by the preparation method of the medicine balloon is applied to the stenosis expansion and restenosis inhibition of blood vessels, urethra or ureteral cavities; the blood vessels include coronary vessels, peripheral vessels, intracranial vessels, and arteriovenous fistula vessels; the urethra includes prostatic urethra, bulbar urethra, membranous urethra, and penile urethra.
The technical scheme of the invention has the following advantages:
1. according to the drug coating provided by the invention, the phenolic compound or the pyrone compound is used as a new carrier, so that the carrier selection efficiency of the drug coating is improved, ideal needle-shaped or columnar crystals can be obtained, the quality of the drug coating is obviously improved, the retention time of the drug in the treatment of vascular or other luminal stenosis diseases is prolonged, and the restenosis of the blood vessel is better inhibited when the drug balloon catheter is used for treating vascular stenosis.
2. The drug coating provided by the invention has the advantages that the selection range of the drug coating formula is reduced, the formula selection process is simplified, the coating preparation method is simple, and the firmness of the drug coating is greatly improved.
3. The drug balloon provided by the invention is applied to the stenosis expansion and restenosis inhibition of blood vessels, urethra and ureteral cavities.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a scanning electron micrograph of a drug coating according to example 1 provided by the present invention; the scale in the figure is 5 μm;
FIG. 2 is a scanning electron micrograph of a drug coating according to comparative example 1 provided by the present invention; the scale in the figure is 10 μm.
Detailed Description
The following examples are provided to further understand the present invention, not to limit the scope of the present invention, but to provide the best mode, not to limit the content and the protection scope of the present invention, and any product similar or similar to the present invention, which is obtained by combining the present invention with other prior art features, falls within the protection scope of the present invention.
The examples do not indicate specific experimental procedures or conditions, and can be performed according to the procedures or conditions of the conventional experimental procedures described in the literature in the field. The reagents or instruments used are conventional reagent products which are commercially available, and manufacturers are not indicated.
The balloon material used in the embodiment of the invention is a self-made balloon made of nylon material, and the specific preparation method comprises the following steps:
preforming: two ends of the balloon material pipe are thinned, and a certain proportion of bubble length is reserved in the middle to obtain a preformed balloon;
molding a mold: and (3) placing the preformed balloon into a balloon mold for blow molding, and filling nitrogen into the preformed balloon, wherein the temperature of the balloon mold is controlled to be 110-400 psi, and the pressure of the nitrogen in the preformed balloon is controlled to be 300-400 psi.
The tea polyphenol product used in the embodiment of the invention is T821916 which is purchased from Mecline;
the maltol used in the examples of the invention was sold under the trade designation M813318, available from Michael;
eugenol used in the embodiment of the invention has a cargo number of E809010 and is purchased from Mecline;
ethyl maltol used in the examples of the invention was sold under the trade designation E824420 and was obtained from Michael.
Example 1
The embodiment provides a drug coating, which comprises a drug and a carrier, wherein the drug is paclitaxel, the carrier is tea polyphenol, a solvent is acetone, the mass ratio of the drug to the carrier is 25:1, and the mass ratio of the drug to the solvent is 30: 1.
The embodiment provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the specific preparation method comprises the following steps:
s1, dissolving the drug and the carrier into a solvent, stirring for 3min, ultrasonically oscillating for 15min at the ultrasonic frequency of 100Hz and the temperature of 30 ℃, and then standing the oscillated solution for 0.5 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method;the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal drug amount of the balloon obtained by spraying is 1 mu g/mm2。
Example 2
The embodiment provides a drug coating, which comprises a drug and a carrier, wherein the drug is paclitaxel, the carrier is maltol, a solvent is acetone, the mass ratio of the drug to the carrier is 20:1, and the mass ratio of the drug to the solvent is 30: 1.
the embodiment provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the specific preparation method comprises the following steps:
s1, dissolving the drug and the carrier into a solvent, stirring for 3min, and ultrasonically oscillating for 15min at the ultrasonic frequency of 100Hz and the temperature of 30 ℃, and then standing the oscillated solution for 1 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal medicine amount of the balloon obtained by spraying is 1 mu g/mm 2。
Example 3
The embodiment provides a drug coating, which comprises a drug and a carrier, wherein the drug is paclitaxel, the carrier is eugenol, a solvent is acetonitrile, the mass ratio of the drug to the carrier is 1:10, and the mass ratio of the drug to the solvent is 500: 1.
the embodiment provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the specific preparation method comprises the following steps:
s1, dissolving the drug and the carrier into a solvent, stirring for 3min, and ultrasonically oscillating for 15min at the ultrasonic frequency of 100Hz and the temperature of 30 ℃, and then standing the oscillated solution for 1 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal drug amount of the balloon obtained by spraying is 1 mu g/mm2。
Example 4
The embodiment provides a drug coating, which comprises a drug and a carrier, wherein the drug is paclitaxel, the carrier is ethyl maltol, a solvent is isopropanol, the mass ratio of the drug to the carrier is 100:1, and the mass ratio of the drug to the solvent is 1: 50.
the embodiment provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the preparation method of the specific drug coating comprises the following steps:
S1, dissolving the drug and the carrier into a solvent, stirring for 3min, and ultrasonically oscillating for 15min at the ultrasonic frequency of 100Hz and the temperature of 30 ℃, and then standing the oscillated solution for 1 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal drug amount of the balloon obtained by spraying is 1 mu g/mm2。
Example 5
The embodiment provides a drug coating, which includes a drug and a carrier, wherein the drug is a paclitaxel derivative, the paclitaxel derivative is docetaxel (with a specific product number of D807092, available from michelin), the carrier is maltol, a solvent is acetone, a mass ratio of the drug to the carrier is 20:1, and a mass ratio of the drug to the solvent is 30: 1.
the embodiment provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the preparation method of the specific drug coating comprises the following steps:
s1, dissolving the drug and the carrier into a solvent, stirring for 3min, and ultrasonically oscillating for 15min at the ultrasonic frequency of 100Hz and the temperature of 30 ℃, and then standing the oscillated solution for 1 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal drug amount of the balloon obtained by spraying is 1 mu g/mm 2。
Example 6
The embodiment provides a drug coating, which comprises a drug and a carrier, wherein the drug is rapamycin, the carrier is maltol, a solvent is acetone, the mass ratio of the drug to the carrier is 20:1, and the mass ratio of the drug to the solvent is 30: 1.
the embodiment provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the preparation method of the specific drug coating comprises the following steps:
s1, dissolving the drug and the carrier into a solvent, stirring for 3min, ultrasonically vibrating for 15min at the ultrasonic frequency of 100Hz and the temperature of 30 ℃, and then standing the vibrated solution for 1.5 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal medicine amount of the balloon obtained by spraying is 1 mu g/mm2。
Example 7
The embodiment provides a drug coating, which includes a drug and a carrier, wherein the drug is a rapamycin derivative, the rapamycin derivative is zotarolimus (with a cargo number of Z872686, available from macelin), the carrier is maltol, a solvent is acetone, a mass ratio of the drug to the carrier is 20:1, and a mass ratio of the drug to the solvent is 30: 1.
the embodiment provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the preparation method of the specific drug coating comprises the following steps:
S1, dissolving the drug and the carrier into a solvent, stirring for 3min, ultrasonically oscillating for 15min at the ultrasonic frequency of 100Hz and the temperature of 30 ℃, and then standing the oscillated solution for 1.5 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal drug amount of the balloon obtained by spraying is 1 mu g/mm2。
Comparative example 1
The comparative example provides a drug coating comprising a drug and a carrier, the drug being paclitaxel, the carrier being sorbitol (sorbitol cat # D817607, available from macelin), the solvent being acetone, the mass ratio of the drug to the carrier being 25:1, the mass ratio of the drug to the solvent being 30: 1.
the comparative example provides a drug balloon obtained by coating the drug coating on the surface of the balloon, and the preparation method of the specific drug coating comprises the following steps:
s1, dissolving the drug and the carrier into the solvent, stirring for 3min, ultrasonically oscillating for 15min, and standing the oscillated solution for 0.5 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal medicine amount of the balloon obtained by spraying is 1 mu g/mm 2。
Comparative example 2
The comparative example provides a drug coating, which comprises a drug and a carrier, wherein the drug is paclitaxel, the carrier is ethyl maltol, a solvent is propanol, the mass ratio of the drug to the carrier is 110:1, and the mass ratio of the drug to the solvent is 1: 50.
the comparative example provides a drug balloon, which is obtained by coating the drug coating on the surface of the balloon, and the preparation method of the specific drug coating comprises the following steps:
s1, dissolving the drug and the carrier into a solvent, stirring for 3min, ultrasonically oscillating for 15min, and standing the oscillated solution for 1 h;
s2, spraying the solution on the surface of the balloon by an ultrasonic spraying method; the spraying pressure is 0.01MPa, the spraying flow rate is 0.03mL/min, and the nominal drug amount of the balloon obtained by spraying is 1 mu g/mm2。
Test example 1
The morphology of the drug coatings obtained in example 1 and comparative example 1 was observed by using a Scanning Electron Microscope (SEM), and the morphology thereof is shown in fig. 1 and fig. 2, and as shown in fig. 1 and fig. 2, the drug coating in fig. 1 forms crystals with crystal morphology growing vertically, the size of the crystals is uniform, and the size is mainly distributed around 5 μm, which enables the drug coating to better fit with the lumen wall when the drug coating expands in a blood vessel, urethra or ureter, more crystals can attach to the lumen wall, and the metabolic time of the crystals in the tissue is longer; in FIG. 2, the crystals formed are undesirable, mostly crystalline, less than 1 μm in size, and have a short metabolic time in the tissue.
Test example 2
Selecting balloons with the size of 2.75 x 12mm, respectively obtaining the drug balloons according to the methods of examples 1-7 and comparative examples 1-2, and testing the retention time of the drug balloons in blood vessels, wherein the specific test method comprises the following steps: and carrying out animal in-vivo test on the drug balloon, wherein the selected animal is a white pig with the weight of about 30kg, the test blood vessel part is a coronary blood vessel, the drug coating balloon is conveyed to the position of the coronary artery of the animal, the drug balloon is taken out after 30s of expansion, the drug content of the blood vessel tissue of the expansion section is tested at 30 days, and the residual drug content ratio is calculated. The ratio of the residual drug content to the tissue drug content/the nominal balloon surface drug amount is multiplied by 100%, and the test results are shown in table 1;
the method for testing the drug content of the vascular tissue of the expansion section comprises the following steps: obtaining blood vessel tissue, grinding the supporting tissue homogenate at 1000r/min by using a tissue triturator, adding the tissue homogenate into 5mL of a mixed solution of methanol and acetonitrile (wherein the volume ratio of the methanol to the acetonitrile is 1:1), then adding 200 mug of an internal standard medicament (the internal standard medicament is the medicament used in the corresponding example or the comparative example), vortexing for 1min, centrifuging for 15min under the condition of 4000r/min to obtain a supernatant, diluting the supernatant by using a 1:1 solvent (volume ratio) of methanol and water, diluting the supernatant twice, and testing by using a liquid chromatography-mass spectrometry combination to obtain tissue medicament concentration data.
TABLE 1 intravascular test results for examples 1-7 and comparative examples 1-2
Group of samples Tissue drug content (μ g/g) for 30 days The content ratio of the rest drugs (esi)
Example 1 10.2 9.8
Example 2 7.8 7.5
Example 3 8.5 8.2
Example 4 14.0 13.5
Example 5 6.9 6.7
Example 6 9.2 8.9
Example 7 7.8 6.9
Comparative example 1 0.6 0.6
Comparative example 2 0.3 0.3
As shown in Table 1, the retention of the drugs in examples 1 to 7 in coronary vessels for 30 days was 10.45. + -. 3.55. mu.g/g, and the content ratio of the remaining drug was 10.1. + -. 3.4 ‰. The retention amount of the medicine in the comparative examples 1-2 in the coronary vessels for 30 days is 0.45 +/-0.15 mu g/g, and the content proportion of the residual medicine is 0.45 per thousand +/-0.15 per thousand. It can be seen that the drug of the present invention has a higher residence time in the tissue than the control.
Test example 3
Selecting a balloon with the size of 8.0 x 40mm, respectively obtaining a drug balloon according to the methods of examples 1-7 and comparative examples 1-2, and testing the retention time of the drug balloon in the urethra, wherein the specific test method comprises the following steps: carrying out intraurethral dilatation on the drug balloon of a dog (beagle dog with about 15 kg), taking out the drug balloon after 3min of dilatation, then testing the drug content in the urethra of the expansion section at 30 days, and calculating the proportion of the residual drug content; the ratio of the residual drug content to the tissue drug content/the nominal balloon surface drug amount is multiplied by 100%, and the test results are shown in table 2;
The method for testing the drug content in the dilated urethra comprises the following steps: obtaining vascular tissues of urethral tissues, grinding the supporting tissue homogenate at 1000r/min by using a tissue triturator, adding the tissue homogenate into 5mL of a mixed solution of methanol and acetonitrile (wherein the volume ratio of the methanol to the acetonitrile is 1:1), then adding 200 mu g of an internal standard medicament (the internal standard medicament is the medicament used in the corresponding example or the comparative example), vortexing for 1min, centrifuging for 15min at 4000r/min to obtain a supernatant, diluting the supernatant by using a 1:1 solvent (volume ratio) of methanol and water, diluting the supernatant twice, and testing by using a liquid chromatography-mass spectrometry to obtain tissue medicament concentration data.
TABLE 2 in-urethral test results of examples 1 to 7 and comparative examples 1 to 2
Group of samples Tissue drug content (μ g/g) for 30 days Residual medicine content ratio (‰)
Example 1 16.2 8.1
Example 2 18.3 9.1
Example 3 19.2 9.6
Example 4 18.1 9.0
Example 5 18.6 9.3
Example 6 15.6 7.8
Example 7 16.1 8.0
Comparative example 1 0.8 0.4
Comparative example 2 0.5 0.5
As shown in Table 2, the drug of examples 1 to 7 had a tissue retention in the urethra of 17.4. + -. 1.8. mu.g/g for 30 days and a residual drug content ratio of 8.6%. + -. 0.9%; the drug of comparative examples 1-2 had a tissue retention in the urethra of 0.65. + -. 0.15. mu.g/g for 30 days, and the remaining drug content ratio was 0.45%. + -. 0.05%. It can be seen that the drug of the present invention has a higher residence time in the tissue than the control.
Test example 4
Selecting balloons with the size of 4.0 multiplied by 20mm, respectively obtaining the drug balloons according to the methods of the examples 1-7 and the comparative examples 1-2, and testing the drug release rate of the drug balloons, wherein the specific test method comprises the following steps: immersing a simulated blood vessel with a proper size into bovine serum albumin (PBS) simulated solution, then respectively extending the drug saccules into the simulated blood vessel and expanding to the explosion pressure (12atm), maintaining the pressure for 60s, then releasing the pressure, taking out the expanded drug saccules from the solution, putting the drug saccules into a 5mL brown volumetric flask, adding 5mL methanol, and standing for half an hour to obtain the elution solution of the drug. Then, the drug content of the eluted solution was measured by using a high performance liquid chromatograph, and the residual drug rate was calculated, and the test results are shown in table 3.
The preparation method of the bovine serum albumin PBS simulated solution comprises the following steps: 10g of bovine serum albumin was weighed and added to 100mL of PBS buffer to prepare a bovine serum albumin solution of 0.1 g/mL. The preparation method of the PBS buffer solution comprises the following steps: weighing 8g NaCl, 0.2g KCl and 1.44g Na2HPO4And 0.24g KH2PO4Dissolving in 800ml distilled water, adjusting pH value of the solution to 7.4 with HCl, and adding distilled water to constant volume to 1L.
Residual drug rate 1-measured drug content/nominal drug content of the drug balloon.
By the same method, the content of the drug in the simulated blood vessel after the drug balloon expansion is measured to obtain the drug release rate, and the specific calculation formula is as follows:
drug release rate-detected drug content/nominal drug content of drug balloon
Drug loss 1-residual drug rate-drug release rate
TABLE 3 in vitro drug Release simulation test results
Group of samples Drug Release Rate (%) Residual dose rate (%) Loss of drug (%)
Example 1 98.1 1.4 0.5
Example 2 97.5 2.0 0.5
Example 3 99.2 0.4 0.4
Example 4 98.3 1.3 0.4
Example 5 97.8 1.6 0.6
Example 6 99.0 0.3 0.7
Example 7 98.7 1.0 1.3
Comparative example 1 78.2 10.4 11.4
Comparative example 2 81.1 9.6 9.3
As shown in Table 3, the in vitro drug release rate of examples 1-7 was 98.35% + -0.85%, the residual drug rate was 1.15% + -0.85%, and the drug loss was 0.85% + -0.45%; the in vitro drug release rate of comparative examples 1-2 was 79.65% + -1.45%, the residual drug rate was 10% + -0.4%, and the drug loss was 10.35% + -1.05%. It can be seen that the drug release rate of the present invention is higher than the control, and both the residual drug rate and the drug loss are lower than the control.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims (12)

1. The drug coating comprises a drug and a carrier, and is characterized in that the carrier is a phenolic compound or a pyrone compound, and the mass ratio of the drug to the carrier is 1 (0.01-10).
2. The drug coating of claim 1, wherein the phenolic compound is selected from at least one of eugenol, thymol, grape polyphenol, tea polyphenol and thymol; the pyrone compound is selected from at least one of maltol, ethyl maltol, coumarin, tartaric acid, flavone and flavonoid compounds;
optionally, the carrier is selected from at least one of eugenol, tea polyphenol, thymol, maltol, ethyl maltol and tartaric acid.
3. A drug coating according to claim 1 or 2, wherein said drug is selected from at least one of paclitaxel, rapamycin, paclitaxel derivatives and rapamycin derivatives.
4. A drug balloon obtained by coating the balloon surface with a drug coating according to any one of claims 1 to 3.
5. A preparation method of a drug balloon, which is characterized in that the drug balloon is the drug balloon of claim 4, and the preparation method comprises the following steps:
Dissolving a drug and a carrier into a solvent to obtain a solution;
the solution is applied to the balloon surface to form a drug coating.
6. The method for preparing a drug balloon according to claim 5, wherein the solvent is at least one selected from water, alcohol compounds, aliphatic hydrocarbon compounds, ether compounds, halogenated hydrocarbon compounds, ketone compounds, tetrahydrofuran and acetonitrile;
optionally, the aliphatic hydrocarbon compound comprises n-hexane and/or n-butane; the ether compounds comprise diethyl ether and/or propylene oxide; the halogenated hydrocarbon compound comprises chloroform; the ketone compound comprises acetone and/or methyl butanone.
7. The method for preparing a drug balloon according to claim 5 or 6, wherein the mass ratio of the drug to the solvent is 1 (0.002-50).
8. The method for preparing a drug balloon according to any one of claims 5-7, wherein the alcohol compound is a compound with a carbon number of less than or equal to 15;
optionally, the alcohol compound is at least one selected from ethanol, methanol, isopropanol, propanol, n-butanol, isobutanol and sec-butanol.
9. The method for preparing a drug balloon according to any one of claims 5 to 8, wherein in the dissolving step, the drug and the carrier are added into the solvent, and then stirring, ultrasonic vibration and standing are performed.
10. The method for preparing a drug balloon according to claim 9, wherein the resting time is 0.5-1.5 h.
11. A method of manufacturing a drug balloon according to any of claims 5-10, wherein the coating comprises spraying, dipping or dropping.
12. The medicinal balloon prepared by the preparation method of the medicinal balloon as claimed in any one of claims 5 to 11 is applied to the stenosis expansion and restenosis inhibition of blood vessels, urethra or ureter lumens; the blood vessels include coronary vessels, peripheral vessels, intracranial vessels, and arteriovenous fistula vessels; the urethra includes prostatic urethra, bulbar urethra, membranous urethra, and penile urethra.
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101239216A (en) * 2008-02-20 2008-08-13 上海赢生医疗科技有限公司 Novel sacculus dilating catheter
CN101808676A (en) * 2007-08-03 2010-08-18 因瓦泰克技术中心有限公司 Improved pharmaceutical-coated medical products, the production thereof and the use thereof
WO2011076196A1 (en) * 2009-12-22 2011-06-30 Cardionovum Sp.Z.O.O. Frankincense and boswellic acids as a coating for stents and catheter balloons
WO2014008875A1 (en) * 2012-07-12 2014-01-16 Cardionovum Gmbh Catheter balloon, method for producing a coated catheter balloon and use of the pharmacological active ingredient
CN105324146A (en) * 2013-04-22 2016-02-10 伊诺拉两合有限公司 Balloon catheter
CN210159073U (en) * 2018-04-12 2020-03-20 中国医学科学院阜外医院 Balloon component for bifurcation lesion of biological body pipeline

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101808676A (en) * 2007-08-03 2010-08-18 因瓦泰克技术中心有限公司 Improved pharmaceutical-coated medical products, the production thereof and the use thereof
CN101239216A (en) * 2008-02-20 2008-08-13 上海赢生医疗科技有限公司 Novel sacculus dilating catheter
WO2011076196A1 (en) * 2009-12-22 2011-06-30 Cardionovum Sp.Z.O.O. Frankincense and boswellic acids as a coating for stents and catheter balloons
WO2014008875A1 (en) * 2012-07-12 2014-01-16 Cardionovum Gmbh Catheter balloon, method for producing a coated catheter balloon and use of the pharmacological active ingredient
CN105324146A (en) * 2013-04-22 2016-02-10 伊诺拉两合有限公司 Balloon catheter
CN210159073U (en) * 2018-04-12 2020-03-20 中国医学科学院阜外医院 Balloon component for bifurcation lesion of biological body pipeline

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