CN112642045A - Drug coating conveying device and preparation method thereof - Google Patents
Drug coating conveying device and preparation method thereof Download PDFInfo
- Publication number
- CN112642045A CN112642045A CN202110026602.4A CN202110026602A CN112642045A CN 112642045 A CN112642045 A CN 112642045A CN 202110026602 A CN202110026602 A CN 202110026602A CN 112642045 A CN112642045 A CN 112642045A
- Authority
- CN
- China
- Prior art keywords
- drug
- delivery device
- drug coating
- antiproliferative
- coating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
-
- 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
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0069—Devices for implanting pellets, e.g. markers or solid medicaments
-
- 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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
- 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
- A61M2207/00—Methods of manufacture, assembly or production
Abstract
The invention provides a drug coating conveying device and a preparation method thereof, belonging to the field of medical instruments, wherein the conveying device comprises a conveying device body, the surface of the conveying device body is provided with a drug coating, the drug coating comprises an antiproliferative drug, an excipient and a stabilizer, and the stabilizer is one or more of butyl hydroxy anisole, dibutyl hydroxy toluene, propyl gallate, tocopherol, ascorbic acid and sodium salt thereof, phytic acid and disodium ethylene diamine tetraacetate; the drug coating is prepared by dissolving and dripping a crystallization solvent; by adding the stabilizer, the solution stability and firmness of the drug coating are obviously improved, and the amount of the drug delivered to the target lesion site is improved.
Description
Technical Field
The invention relates to the field of medical instruments, in particular to a drug coating conveying device and a preparation method thereof.
Background
Atherosclerosis-induced lower extremity arterial disease is an important component of global disease that currently leads to death and disability. The estimated 1600-2400 million patients with lower limb artery disease in the United states need surgical treatment about 10 million times per year, and the prevalence rate of the lower limb artery disease is basically the same as that of coronary heart disease. With the increase of age, the incidence rate of artery diseases of lower limbs is obviously increased, wherein the incidence rate of artery diseases of 45-54 years old is 0.6%, the incidence rate of artery diseases of 55-64 years old is 2.5%, and the incidence rate of artery diseases of 65-74 years old is 8.8%. The lower limb artery disease seriously damages the function of the affected limb and threatens the life quality of the patient, is easy to combine coronary artery, intracranial artery and renal artery diseases, and obviously increases the risks of myocardial infarction, cerebral apoplexy, aortic aneurysm and ischemic ulcer; the severe lower limb arterial ischemia caused by the diabetic foot enables the amputation rate to reach 33%, the death rate to exceed 20%, and the amputation rate of patients with 65-74 years old complicated with diabetes is nearly 20 times of that of normal people. Active prevention and health care of ischemic diseases of middle-aged and elderly people are very slow.
Vascular injury from conventional angioplasty in turn leads to intimal hyperplasia leading to late loss of lumen and consequent restenosis. The drug coating delivery device is loaded with anti-intimal hyperplasia drugs to inhibit intimal hyperplasia and prevent restenosis. The drug coating delivery device has significant effect, can greatly reduce the restenosis rate in the blood vessel, does not need to be reused, and simultaneously reduces the pain of patients. Current drug coating delivery devices all inevitably suffer from problems such as: (1) the firmness of the drug coating is not good enough, most drugs are lost before reaching the target lesion blood vessel, the antiproliferative drug with enough dosage can not act on the blood vessel, and the utilization rate is low; and (2) the stability of the drug coating solution is poor, and the production efficiency is low.
Disclosure of Invention
At least one of the above problems is addressed by the present invention, which provides a drug-coated delivery device and a method for making the same.
The purpose of the invention is realized by adopting the following technical scheme:
a drug coating delivery device comprises a delivery device body, wherein a drug coating is arranged on the surface of the delivery device body, and comprises an antiproliferative drug, an excipient and a stabilizer.
Preferably, the antiproliferative drug comprises one or more of nimustine, carmustine, 5-fluorouracil, fluoroguanosine, gemcitabine, daunorubicin, doxorubicin, paclitaxel, vinblastine, topotecan, aminoglutethimide, sirolimus, everolimus and zotarolimus.
Preferably, the excipient is one or more of shellacamine salt, citric acid, resveratrol, polybutylmethacrylate, stearic acid, magnesium stearate, sodium stearate, zinc stearate, stearamide, isooctyl palmitate, linoleic acid, linolenic acid, glycerol monooleate, iohexol, iopromide, urea, sorbitol, polysorbitol, trihexyl citrate, phospholipids, ropiperazine base, cholesterol, vitamin E polyethylene glycol succinate.
Preferably, the stabilizer is one or more of butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, tocopherol, ascorbic acid and sodium salt thereof, phytic acid and disodium ethylene diamine tetraacetate.
Preferably, the mass ratio of the antiproliferative drug to the excipient in the drug coating is (0.5-200): 1.
preferably, the mass ratio of the antiproliferative drug to the stabilizer in the drug coating is (0.5-500): 1.
preferably, the content of the antiproliferative drug in the drug coating is 0.1-50 mug/mm2。
The invention also provides a preparation method of the drug coating conveying device, which comprises the steps of mixing the antiproliferative drug, the excipient, the stabilizer and the crystallization solvent to prepare a drug coating solution, uniformly dripping the drug coating solution on the surface of the conveying device body, and drying to obtain the drug coating conveying device; the crystallization solvent comprises a first solvent and a second solvent, wherein the first solvent is one or more of acetone, isopropanol, ethanol, methanol and n-heptane, and the second solvent is one or more of acetic acid, tetrahydrofuran, acetonitrile, n-propyl acetate and ethyl acetate.
The drug coating delivery device can deliver the antiproliferative drug to blood vessels or lumens, wherein the blood vessels comprise coronary artery blood vessels, peripheral artery blood vessels or cerebral artery blood vessels; the lumen comprises esophagus, airway, intestinal tract, biliary tract, cervix, urinary tract or prostate; the peripheral arterial vessels include the leg arteries, further, the iliac, external iliac, femoral or popliteal arteries.
The invention has the beneficial effects that:
(1) according to the invention, the stabilizer is added into the drug coating solution, so that the decomposition resistance of the active drug in the drug coating solution can be obviously improved, the storage stability of the drug coating solution in the production and preparation process is improved, and the effective period of the solution is prolonged.
(2) According to the invention, the stabilizer is added into the drug coating solution, so that the firmness of the drug coating is remarkably improved, the drug loss of the drug coating conveying device in the conveying process is greatly reduced, more drugs can be conveyed to the target lesion position, the intimal hyperplasia is effectively inhibited, and the restenosis is reduced.
(3) The drug coating formula without the polymer can effectively reduce the vascular inflammatory reaction, thereby reducing the vascular endothelialization delay and the risk of late vascular stenosis.
(4) Most of the existing drug coatings are in a non-crystalline disordered state, the storage capacity of target lesion blood vessels is low, the retention time is short, the application shows that the drug coatings are prepared by dissolving and dripping a crystallization solvent to obtain a fully or partially crystalline ordered microcrystalline structure coating, the dissolution rate of the drug coatings is improved, and meanwhile, the crystalline drug coatings are higher in bioavailability, easier to absorb and longer in vascular wall retention time than non-crystalline drug coatings, so that the long-term patency rate is improved.
Drawings
The invention is further illustrated by means of the attached drawings, but the embodiments in the drawings do not constitute any limitation to the invention, and further drawings may be obtained by those skilled in the art without inventive effort, based on the following drawings.
FIG. 1 is a schematic structural view of a balloon catheter of the rapid exchange (Rx) configuration;
FIG. 2 is a schematic structural view of the balloon catheter of the double-lumen structure;
FIG. 3 is a schematic structural view of the semi-finished stent;
FIG. 4 is an SEM image of the drug coating described in example 1;
FIG. 5 is an SEM image of the drug coating described in example 2;
FIG. 6 is an SEM image of the drug coating described in example 3;
FIG. 7 is an SEM image of the drug coating described in example 4;
FIG. 8 is an SEM image of the drug coating described in example 5;
FIG. 9 is an SEM image of the drug coating of comparative example 1;
figure 10 is a line graph of in vitro dissolution for the drug coatings described in examples 1-5 and comparative example 1.
Reference numerals: 11-tip; 12-a balloon; 13-an identification ring; 14-a shaft rod; 15-a marker band; 16-a catheter hub; 21-a catheter hub; 22-shaft rod; 23-a balloon; 24-a tip; 25-marker loop; 31-a handle; 32-a conveying rod; 33-stent coating segment.
Detailed Description
The invention is further described with reference to the following examples.
Example 1
Mixing 50mg of paclitaxel and 50mg of everolimus as antiproliferative drugs, 5mg of iopromide as an excipient and 1mg of tocopherol as a stabilizer with 23ml of ethanol, 19ml of n-heptane and 8ml of tetrahydrofuran to prepare a drug coating solution; taking a balloon catheter with a rapid exchange (Rx) structure (shown in figure 1), and pressurizing to a nominal pressure; uniformly dripping a certain volume of drug coating solution on the surface of the balloon by using a precise liquid preparation instrument under a ten thousand grade clean environment to ensure that the total content of the drugs (comprising paclitaxel and elvan) on the balloonSi) up to 10. mu.g/mm2(ii) a After coating, the saccule is folded while negative pressure is pumped, and a PTFE protective tube is sleeved; drying the folded saccule in a constant temperature and humidity box for at least 12 hours, wherein the temperature is set to be 40 +/-2 ℃, and the humidity is set to be 60% +/-5%; packaging and sterilizing with ethylene oxide to obtain the drug-coated balloon dilatation catheter of the embodiment; in the embodiment, the antiproliferative drug is paclitaxel and everolimus in a ratio of 1:1, the ratio of the antiproliferative drug to the excipient is 20:1, and the ratio of the antiproliferative drug to the stabilizer is 100: 1;
referring to fig. 1, the balloon catheter in the rapid exchange (Rx) configuration is comprised of a tip 11, a balloon 12, an identification ring 13, a shaft 14, a marker band 15, and a catheter hub 16.
Example 2
Mixing 100mg of paclitaxel as an antiproliferative drug, 10mg of polysorbitol as an excipient and 2mg of tocopherol as a stabilizer with 23ml of ethanol, 19ml of n-heptane and 8ml of tetrahydrofuran to prepare a drug coating solution; taking a balloon catheter (shown in figure 2) with a double-cavity structure, and pressurizing to a nominal pressure; uniformly dripping a certain volume of drug coating solution on the surface of the balloon by using a precise liquid preparation instrument under a ten thousand grade clean environment to ensure that the total content of the paclitaxel drug on the balloon reaches 10 mu g/mm2(ii) a After coating, the saccule is folded while negative pressure is pumped, and a PTFE protective tube is sleeved; drying the folded balloon in a constant temperature and humidity box for at least 12 hours, wherein the temperature is set to be 40 +/-2 ℃, and the humidity is set to be 60% +/-5%; packaging and sterilizing with ethylene oxide to obtain the drug-coated balloon dilatation catheter of the embodiment; in this example, the antiproliferative drug is paclitaxel, the ratio of antiproliferative drug to excipient is 10:1, and the ratio of antiproliferative drug to stabilizer is 50: 1;
referring to fig. 2, the balloon catheter of the double lumen structure is composed of a catheter hub 21, a shaft 22, a balloon 23, a tip 24 and a marker ring 25.
Example 3
Mixing 200mg of sirolimus as an antiproliferative drug, 4mg of magnesium stearate as an excipient and 2mg of tocopherol as a stabilizer with 59ml of acetone, 33ml of n-heptane and 8ml of tetrahydrofuran to prepare a drug coating solution; is taken out completelyUniformly dripping a certain volume of drug coating solution on the surface of the stent by using a precise liquid preparation instrument under a ten thousand-grade clean environment to ensure that the total content of sirolimus drug on the stent reaches 10 mu g/mm2(ii) a After coating, loading the stent on the surface of the balloon, pumping negative pressure to the balloon, folding the balloon and the stent, and then sleeving a PTFE protective tube; drying the folded bracket in a constant temperature and humidity box for at least 12 hours, wherein the temperature of the constant temperature box is set to be 40 +/-2 ℃, and the humidity is set to be 60% +/-5%; packaging and sterilizing with ethylene oxide to obtain the drug-coated spherical stent of the embodiment; in the embodiment, the antiproliferative drug is sirolimus, the proportion of the antiproliferative drug to the excipient is 50:1, and the proportion of the antiproliferative drug to the stabilizer is 100: 1;
referring to fig. 3, the semi-finished stent consists of a handle 31, a delivery rod 32 and a stent coating segment 33.
Example 4
Mixing 200mg of paclitaxel as an antiproliferative drug, 2mg of magnesium stearate as an excipient and 1mg of butylated hydroxytoluene as a stabilizer with 59ml of acetone, 33ml of n-heptane and 8ml of tetrahydrofuran to prepare a drug coating solution; a balloon catheter of a rapid exchange (Rx) structure (same as in example 1) was taken and pressurized to a nominal pressure; uniformly dripping a certain volume of drug coating solution on the surface of the balloon by using a precise liquid preparation instrument under a ten thousand-grade clean environment to ensure that the total content of the paclitaxel drug on the balloon reaches 10 mu g/mm2(ii) a After coating, the saccule is folded while negative pressure is pumped, and a PTFE protective tube is sleeved; drying the folded saccule in a constant temperature and humidity box for at least 12 hours, wherein the temperature of the constant temperature box is set to be 40 +/-2 ℃, and the humidity is set to be 60% +/-5%; packaging and sterilizing with ethylene oxide to obtain the drug-coated balloon dilatation catheter of the embodiment; in this example, the antiproliferative drug is paclitaxel, the ratio of antiproliferative drug to excipient is 100:1, and the ratio of antiproliferative drug to stabilizer is 200: 1.
Example 5
140mg of everolimus as an antiproliferative drug, 7mg of trihexyl citrate as an excipient, 2mg of tocopherol as a stabilizer, 35ml of ethanol, 23ml of n-heptane, 8ml of tetrakisMixing hydrogen furan with 4ml acetic acid to prepare a drug coating solution; taking a balloon catheter with a double-cavity structure (same as the embodiment 2), and pressurizing to a nominal pressure; uniformly dripping a certain volume of drug coating solution on the surface of the balloon by using a precise liquid preparation instrument under a ten thousand-level clean environment to ensure that the total content of everolimus drugs on the balloon reaches 10 mu g/mm2(ii) a After coating, the saccule is folded while negative pressure is pumped, and a PTFE protective tube is sleeved; drying the folded saccule in a constant temperature and humidity box for at least 12 hours, wherein the temperature of the constant temperature box is set to be 40 +/-2 ℃, and the humidity is set to be 60% +/-5%; packaging and sterilizing with ethylene oxide to obtain the drug-coated balloon dilatation catheter of the embodiment; in this example, the antiproliferative drug is elvucimol, the ratio of antiproliferative drug to excipient is 20:1, and the ratio of antiproliferative drug to stabilizer is 70: 1.
Comparative example 1
Mixing 70mg of sirolimus as an antiproliferative drug and 7mg of iopromide as an excipient with 35ml of ethanol to prepare a drug coating solution; taking a balloon catheter with a double-cavity structure (same as the embodiment 2), and pressurizing to a nominal pressure; uniformly dripping a certain volume of drug coating solution on the surface of the balloon by using a precise liquid preparation instrument under a ten thousand grade clean environment to ensure that the total content of sirolimus drug on the balloon reaches 10 mu g/mm2(ii) a After coating, the saccule is folded while negative pressure is pumped, and a PTFE protective tube is sleeved; drying the folded saccule in a constant temperature and humidity box for at least 12 hours, wherein the temperature of the constant temperature box is set to be 40 +/-2 ℃, and the humidity is set to be 60% +/-5%; packaging and sterilizing with ethylene oxide to obtain the drug-coated balloon dilatation catheter of the embodiment; in the present example, the antiproliferative drug was sirolimus, the ratio of antiproliferative drug to excipient was 10:1, and no stabilizer was added.
Experimental example 1
Drug coating solution stability
The drug coating solutions obtained in examples 1 to 5 and comparative example 1 were stored separately, and the drug contents of the solutions were measured at regular intervals of time to perform a solution stability test.
Testing equipment: shimadzu model LC-15C/LC-16 high performance liquid chromatograph.
Chromatographic conditions (paclitaxel): the chromatographic column is C18, 4.6mm × 25cm × 5 μm; the diluent is methanol: acetic acid (200: 1); the mobile phase is water: acetonitrile (11: 9); the detection wavelength is 227 nm; the flow rate is 1.5 mL/min; the sample injection volume is 10 mu L;
chromatographic conditions (sirolimus and everolimus): the chromatographic column is C18, 150X 4.6 mm; the diluent is acetonitrile, and the mobile phase is acetonitrile: water (65: 35) with a column temperature of 60 ℃ and a detection wavelength of 280 nm; the flow rate is 1 mL/min; the injection volume is 20 mu L;
the test results are shown in table 1, the drug content of the drug coating solutions of all the examples is very stable up to 6 months, and the stability of the drug content of the comparative example is poor, which indicates that the drug coating solutions of the examples can better meet the production requirements, frequent preparation of the coating solutions is not required, and the production efficiency and the product stability can be improved.
TABLE 1 percent drug content of the solution (relative to the initial drug solubility)
| Sample (I) | 1 month/%) | 2 month/%) | 3 month/%) | 6 month/%) |
| Example 1 | 99.2 | 99.1 | 99.1 | 98.9 |
| Example 2 | 99.5 | 99.3 | 99.2 | 99.0 |
| Example 3 | 99.1 | 99.0 | 99.0 | 98.8 |
| Example 4 | 99.6 | 99.3 | 99.1 | 99.0 |
| Example 5 | 99.8 | 99.5 | 99.3 | 99.1 |
| Comparative example 1 | 96.3 | 89.4 | 72.5 | 52.3 |
Experimental example 2
Firmness of coating
The actual surgical procedure was simulated by passing the drug-coated balloons or drug-coated stents of examples 1-5 and comparative example 1 through an in vitro simulation model, and then testing the residual drug content of the delivered product (see test example 1 for testing method), and calculating the coating firmness of the product using the following formula:
coating firmness (residual drug content/initial drug content on balloon or stent surface) x 100%
The test results are shown in table 2, all examples have drug firmness of more than 80%, the stent is slightly better than the balloon catheter, and the comparative example has coating firmness of only 53.1%, which is much lower than the test results of the examples. The drug coating delivery device can greatly reduce the drug loss in the delivery process, deliver more drugs to the target lesion blood vessel, effectively inhibit intimal hyperplasia and reduce restenosis.
TABLE 2 coating firmness results
| Sample (I) | Coating firmness results |
| Example 1 | 83.5％ |
| Example 2 | 83.3％ |
| Example 3 | 89.1％ |
| Example 4 | 85.6％ |
| Example 5 | 84.8％ |
| Comparative example 1 | 53.1％ |
Experimental example 3
Crystallinity test
Taking the products of examples 1-5 and comparative example 1, taking off the protective tube, observing the crystal form of the drug coating of the product under the same magnification by using a Scanning Electron Microscope (SEM); the observation results are shown in FIGS. 4-9, from which it can be seen that examples 1-5 are crystalline drug coatings, while comparative example 1 is a non-crystalline drug coating; compared with the non-crystalline drug coating, the crystalline drug coating has higher bioavailability, easier absorption and longer vessel wall retention time, thereby improving the long-term patency rate.
Experimental example 4
In vitro dissolution test
Preparing a dissolution testing apparatus according to the requirements of USP711 method 2 (paddle method); placing 900mL of dissolution medium in a container and placing in a thermostatic water bath at 37 ℃, placing the balloon (examples 1-2, examples 4-5 and comparative example 1) at the bottom of the container, expanding the balloon to a nominal pressure using a pressurizing device, and maintaining the pressure for 60 s; after the pressure maintaining is finished, directly cutting off the joint of the balloon and the shaft lever by using scissors, and putting a stainless steel mesh disc for fixing the balloon into the container; the rotating speed parameter of the instrument is set to be 75 r/min, so that the effective components of the medicine in the balloon sample are dissolved out. The release medium was a buffer solution of 4% bovine serum albumin and 0.1% sodium azide in PBS (PH 7.4, 0.01M); the sampling time is respectively 10min, 30min, 1h, 2h, 4h, 6h and 8 h; after reaching the corresponding time point, using an injector to suck 1mL of solution, and filtering the solution to be used as a test solution to test the drug concentration of the solution (the test method is shown in an experimental example 1); the cumulative dissolved drug content was calculated by the following formula:
cumulative dissolved drug content ═ [ (drug concentration (μ g/mL) × 900 (mL))/initial drug content on balloon surface ] × 100%
The test results are shown in figure 10, and the results show that the in vitro dissolution curves of all the examples are rapid and basically consistent, and the final dissolution endpoint is more than 95%; whereas the in vitro dissolution profile of comparative example 1 was slow and the final dissolution end point was only 50%; this is consistent with the crystallinity test results of experimental example 3, with crystalline coatings (examples 1, 2, 4, 5) being more bioavailable than non-crystalline coatings (comparative example 1), being more readily absorbed and retained by the vessel wall, and thus increasing the rate of long-term patency.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (8)
1. The drug coating delivery device comprises a delivery device body and is characterized in that a drug coating is arranged on the surface of the delivery device body and comprises an antiproliferative drug, an excipient and a stabilizer.
2. The drug coating delivery device of claim 1, wherein the antiproliferative drug comprises one or more of nimustine, carmustine, 5-fluorouracil, fluoroguanosine, gemcitabine, daunorubicin, doxorubicin, paclitaxel, vinblastine, topotecan, aminoglutethimide, sirolimus, everolimus, zotarolimus.
3. The drug-coated delivery device of claim 1, wherein the excipient is one or more of shellacamine salt, citric acid, resveratrol, polybutylmethacrylate, stearic acid, magnesium stearate, sodium stearate, zinc stearate, stearamide, isooctyl palmitate, linoleic acid, linolenic acid, glycerol monooleate, iohexol, iopromide, urea, sorbitol, polysorbitol, trihexyl citrate, phospholipids, ropiperazine matrix, cholesterol, vitamin E polyethylene glycol succinate.
4. The drug coating delivery device of claim 1, wherein the stabilizer is one or more of butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, tocopherol, ascorbic acid and its sodium salt, phytic acid, and disodium ethylenediaminetetraacetate.
5. The drug coating delivery device of claim 1, wherein the mass ratio of the antiproliferative drug to the excipient in the drug coating is (0.5-200): 1.
6. the drug coating delivery device of claim 1, wherein the mass ratio of the antiproliferative drug to the stabilizer in the drug coating is (0.5-500): 1.
7. the drug-coated delivery device of claim 1, wherein the antiproliferative drug is present in the drug-coated layer in an amount of 0.1-50 μ g/mm2。
8. A method for preparing the drug-coated delivery device according to any one of claims 1 to 7, wherein the antiproliferative drug, the excipient, the stabilizer and the crystallization solvent are mixed to prepare a drug-coated solution, the drug-coated solution is uniformly dropped on the surface of the delivery device body, and the drug-coated solution is dried;
the crystallization solvent comprises a first solvent and a second solvent, wherein the first solvent is one or more of acetone, isopropanol, ethanol, methanol and n-heptane, and the second solvent is one or more of acetic acid, tetrahydrofuran, acetonitrile, n-propyl acetate and ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110026602.4A CN112642045A (en) | 2021-01-08 | 2021-01-08 | Drug coating conveying device and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110026602.4A CN112642045A (en) | 2021-01-08 | 2021-01-08 | Drug coating conveying device and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112642045A true CN112642045A (en) | 2021-04-13 |
Family
ID=75367741
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110026602.4A Pending CN112642045A (en) | 2021-01-08 | 2021-01-08 | Drug coating conveying device and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112642045A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115300675A (en) * | 2022-03-21 | 2022-11-08 | 上海以心医疗器械有限公司 | Medical device with drug coating and preparation method and application thereof, drug coating and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264347A (en) * | 2007-11-27 | 2008-09-17 | 天津百畅医疗器械科技有限公司 | Drug-eluting coated on surface of sacculus catheter air bag for alleviating vascular restenosis |
| US20160228617A1 (en) * | 2013-09-18 | 2016-08-11 | Innora Gmbh | Long-Acting Limus Formulation on Balloon Catheters |
| CN106794285A (en) * | 2014-10-03 | 2017-05-31 | W.L.戈尔及同仁股份有限公司 | For the removable covering of the medical treatment device of insoluble drug release |
| CN107073178A (en) * | 2014-07-18 | 2017-08-18 | M.A.医学联合公司 | The coating of expansible conduit in the tube chamber for the contact transfer that medicine pair micro-reservoirs are provided |
| CN111249536A (en) * | 2020-01-15 | 2020-06-09 | 山东瑞安泰医疗技术有限公司 | Novel drug eluting balloon catheter and preparation method thereof |
| CN111298272A (en) * | 2020-03-11 | 2020-06-19 | 科塞尔医疗科技（苏州）有限公司 | Drug-coated balloon, preparation method thereof and drug-coated balloon dilatation catheter |
-
2021
- 2021-01-08 CN CN202110026602.4A patent/CN112642045A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264347A (en) * | 2007-11-27 | 2008-09-17 | 天津百畅医疗器械科技有限公司 | Drug-eluting coated on surface of sacculus catheter air bag for alleviating vascular restenosis |
| US20160228617A1 (en) * | 2013-09-18 | 2016-08-11 | Innora Gmbh | Long-Acting Limus Formulation on Balloon Catheters |
| CN107073178A (en) * | 2014-07-18 | 2017-08-18 | M.A.医学联合公司 | The coating of expansible conduit in the tube chamber for the contact transfer that medicine pair micro-reservoirs are provided |
| CN106794285A (en) * | 2014-10-03 | 2017-05-31 | W.L.戈尔及同仁股份有限公司 | For the removable covering of the medical treatment device of insoluble drug release |
| CN111249536A (en) * | 2020-01-15 | 2020-06-09 | 山东瑞安泰医疗技术有限公司 | Novel drug eluting balloon catheter and preparation method thereof |
| CN111298272A (en) * | 2020-03-11 | 2020-06-19 | 科塞尔医疗科技（苏州）有限公司 | Drug-coated balloon, preparation method thereof and drug-coated balloon dilatation catheter |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115300675A (en) * | 2022-03-21 | 2022-11-08 | 上海以心医疗器械有限公司 | Medical device with drug coating and preparation method and application thereof, drug coating and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11318232B2 (en) | Compositions and methods for delivering drugs to a vessel wall | |
| CN111317907B (en) | Composite drug coating balloon, preparation method thereof and composite drug coating balloon dilatation catheter | |
| US9724497B2 (en) | Method of coating a catheter balloon having a fold | |
| EP2886136B1 (en) | A Coated Angioplasty or Coronary Angioplasty Catheter | |
| US10058636B2 (en) | Drug coated balloon catheter | |
| CN106237395B (en) | A kind of medicine-coated balloon and preparation method thereof | |
| CN111298272A (en) | Drug-coated balloon, preparation method thereof and drug-coated balloon dilatation catheter | |
| JP6573911B2 (en) | Balloon catheter for treatment of peripheral artery disease | |
| WO2016188303A1 (en) | Drug coating layer balloon catheter | |
| EP3030274B1 (en) | Method of treating peripheral artery diseases in lower limbs | |
| JP6573912B2 (en) | Balloon catheter for treatment of peripheral artery disease | |
| EP3174567B1 (en) | Paclitaxel-eluting balloon and method for manufacturing the same | |
| EP2380605A1 (en) | Improved formulations for drug-coated medical devices | |
| WO2016206078A1 (en) | Method for preparing drug balloon | |
| JP6174038B2 (en) | Drug-coated medical device and adjustment method thereof | |
| WO2018059167A1 (en) | Drug-coated balloon | |
| CN112642045A (en) | Drug coating conveying device and preparation method thereof | |
| CN107865868B (en) | New application of amlexanox | |
| CN107995869B (en) | Surface liquefied drug coating sacculus | |
| CN113018649B (en) | Drug delivery catheter and preparation method thereof | |
| TW201620551A (en) | Stent of drug-dissolution type | |
| CN116712615A (en) | Preparation method of coating solution, medicine balloon for non-vascular intervention and preparation method | |
| CN116726356A (en) | Preparation method of drug delivery device and drug delivery device | |
| CN216319435U (en) | Medicine carrying balloon with mark | |
| US20210346658A1 (en) | Active-substance coating for balloons of balloon catheters |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |