Preparation method of balloon coating and drug balloon

Abstract

The invention provides a preparation method of a balloon coating, the preparation method is used for preparing a nifedipine coating on a balloon, and the preparation method is characterized by comprising the following steps: S1, adding nifedipine and iopromide into an organic solvent according to the mass-volume ratio of nifedipine to iopromide being 30-80 mg / ml to 25-45 mg / ml to obtain a nifedipine mixed solution; and S2, coating the nifedipine mixed solution on a preset part of the balloon, and drying to obtain the nifedipine coating coated on the balloon. The invention further provides the medicine balloon prepared by the preparation method. As the balloon body is coated with the balloon coating containing nifedipine, on one hand, excitation-contraction coupling of blood vessels can be inhibited, the blood vessels at the contact part of the balloon body can be expanded, and the vasospasm state can be quickly relieved, so that the balloon is easy to pass through, and the subsequent operation can be smoothly carried out; on the other hand, nifedipine can effectively reduce platelet aggregation and prevent thrombus and arteriosclerosis plaque formation.

Description

Technical Field

[0001] The invention belongs to the technical field of medical devices, and particularly relates to a method for preparing a balloon coating and a drug balloon. Background Art

[0002] Vascular stenosis is a vascular disease that may occur in systemic arteries such as the coronary arteries, cerebral arteries, carotid arteries, and lower limb arteries. Its main causes are atherosclerosis, Takayasu arteritis, and radiotherapy.

[0003] Balloon catheters are used to dilate pathologically narrowed (or blocked) blood vessels. The balloon attached to the vascular catheter is inserted through an artery such as the femoral artery (or coronary artery, etc.), and acts on the narrowed (or blocked) part of the blood vessel under X-ray control. The balloon is then pressurized and slowly deployed, dilating the narrowed (or blocked) part and allowing uninterrupted blood flow, thereby achieving the purpose of treatment.

[0004] However, during interventional surgery, there may be situations where the balloon cannot pass due to vasospasm, or even the operation cannot be performed. When vasospasm occurs, the smooth muscle of the vascular wall contracts strongly, the lumen is narrowed, and the blood flow is reduced. In severe cases, the lumen can be blocked. If the spasm lasts too long, it may even cause vascular embolism. Vasospasm is induced by many factors, including direct vascular manipulation, vascular metabolic imbalance, and changes in the internal environment. These factors can be divided into two categories, namely neurogenic and myogenic. Neurogenic vasospasm is mediated by neurovasoconstrictors, and myogenic vasospasm is mediated by vascular smooth muscles that sense the mechanical force of the vascular wall.

[0005] There are some drugs with vasodilatory effects in the prior art, but such drugs cannot act quickly on local spasmodic blood vessels when taken orally; in addition, the expansion effect of the balloon is a physical effect, and it cannot inhibit the contraction of the vascular smooth muscle itself. It is difficult to pass through areas where the vascular smooth muscle has a strong contraction effect, and may even cause damage to the blood vessels in a contracted state due to excessive expansion. Summary of the invention

[0006] The present invention is made to solve the above-mentioned problems, and aims to provide a drug balloon that directly acts on the site of vascular spasm, so as to relieve vascular spasm, facilitate subsequent surgical operations, and thus greatly increase the success rate of intracavitary treatment.

[0007] The present invention provides a method for preparing a balloon coating, which is used for preparing a nifedipine coating on a balloon and has the following characteristics, comprising the following steps: step S1, adding nifedipine and iopromide into an organic solvent according to a mass volume ratio of 30-80 mg / ml of nifedipine and 25-45 mg / ml of iopromide to obtain a nifedipine mixed solution; step S2, coating the nifedipine mixed solution on a predetermined part of the balloon, and after drying, obtaining the nifedipine coating coated on the balloon.

[0008] The method for preparing the balloon coating provided by the present invention may also have the following feature: wherein the organic solvent is any one of acetone and chloroform or a combination of the two.

[0009] The method for preparing the balloon coating provided by the present invention may also have the following characteristics: wherein iopromide is an aqueous solution with a specification of 100 ml: 76.89 g.

[0010] The method for preparing the balloon coating provided by the present invention may also have the following feature: wherein, in step S2, the nifedipine solution is sprayed onto a predetermined portion of the balloon using a spraying device.

[0011] The present invention also provides a drug balloon having the following characteristics, comprising: a balloon and a nifedipine coating coated on the balloon.

[0012] The drug balloon provided by the present invention may also have the following features: the balloon includes a catheter and a balloon body connected to the catheter, and the nifedipine coating is located on the surface of the balloon body.

[0013] The drug balloon provided by the present invention may also have the following feature: the nifedipine coating is also located on the surface of a portion of the catheter.

[0014] Functions and Effects of the Invention

[0015] According to the preparation method of the balloon coating and the drug balloon provided by the present invention, since the balloon coating containing nifedipine is coated on the balloon body, on the one hand, the nifedipine in the balloon coating can inhibit the excitation-contraction coupling of the blood vessels, dilate the blood vessels in the part where the balloon body contacts, and make the balloon easy to pass; on the other hand, nifedipine can also effectively reduce platelet aggregation, prevent the formation of thrombus and atherosclerotic plaque, and greatly reduce the occurrence time and incidence of postoperative restenosis. In addition, since it also contains iopromide, it can be used as a contrast agent to make the development of the balloon body more obvious during surgery, which is more conducive to the operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a schematic cross-sectional structure diagram of a drug balloon according to an embodiment of the present invention. DETAILED DESCRIPTION

[0017] In order to make the technical means, creative features, objectives and effects achieved by the present invention easy to understand, the preparation method of the drug balloon and the balloon coating of the present invention is specifically described below in conjunction with examples.

[0018] In the present invention, unless otherwise specified, all reagents and drugs used are purchased from general commercial channels. Among them, the CAS number of nifedipine is 21829-25-4; the CAS number of iopromide is 73334-07-3, and the appearance is off-white to white powder.

[0019] In the embodiment, nifedipine tablets are used as the source of nifedipine. The nifedipine tablets are sugar-coated tablets or film-coated tablets. After removing the coating, they are yellow. The main component is nifedipine, and the auxiliary materials are magnesium stearate, etc. Nifedipine tablets are almost insoluble in water, very soluble in acetone and chloroform, and slightly soluble in ethanol. The method for identifying nifedipine is: take about 25 mg of nifedipine tablets, add 1 ml of acetone to dissolve, add 3 to 5 drops of 20% sodium hydroxide solution, shake, and the solution is orange-red.

[0020] The method for preparing a balloon coating provided by the present invention is used to prepare a nifedipine coating on a balloon, and specifically comprises the following steps:

[0021] Step S1, adding the ground nifedipine tablets and iopromide solution into an organic solvent according to the mass volume ratio of nifedipine 30-80 mg / ml and iopromide 25-45 mg / ml to obtain a nifedipine mixed solution;

[0022] Step S2, coating the nifedipine mixed solution on a predetermined position of the balloon, and after drying, obtaining a nifedipine coating coated on the balloon.

[0023] The organic solvent used in step S1 is acetone, chloroform or a mixed solvent thereof.

[0024] In step S2, the nifedipine solution can be sprayed onto the predetermined part of the balloon using an ultrasonic spray device, or the predetermined part of the balloon can be immersed in the nifedipine solution so that the part has a layer of nifedipine coating.

[0025] The above-mentioned balloon is a common clinical balloon, which includes a spherical balloon body and a catheter connected and communicated with the balloon body. The predetermined portion to be coated can be the surface of the balloon body.

[0026] Therefore, ordinary clinical balloons can be coated with a layer of nifedipine coating to obtain drug-containing balloons.

[0027] <Example>

[0028] This example specifically describes the preparation method of the balloon coating and the drug balloon.

[0029] The raw materials and equipment used in this embodiment include:

[0030] Nifedipine tablets: Specification: 30 mg / tablet, source: Bayer Healthcare, Germany;

[0031] Iopromide aqueous solution (i.e., ioopromide injection): specification 100ml: 76.89g, source: Bayer Healthcare Co., Ltd. Guangzhou Branch Bayer Healthcare Co., Ltd. Guangzhou Branch;

[0032] Balloon: Ordinary clinical balloons were used, with specifications of 3.5 / 4.0*200, i.e., the outer diameter of the front end of the balloon was 3.5 mm, the outer diameter of the rear end of the balloon was 4.0 mm, and the length of the balloon was 200 mm. The balloon was sourced from Pulirui Medical Technology Co., Ltd.;

[0033] The ultrasonic spraying equipment specifically adopts a desktop drug balloon sprayer, which is from Beijing Dongfang Jinrong Ultrasonic Electrical Co., Ltd. and the model is UC530.

[0034] Figure 1 It is a schematic cross-sectional structure diagram of a drug balloon according to an embodiment of the present invention.

[0035] like Figure 1 As shown, the drug balloon 100 includes a balloon body 1, a catheter 2 connected to and in communication with the balloon body 1, and a balloon coating 3 coated on the surface of the balloon body 1 and a portion of the catheter 2. In this embodiment, the end of the catheter 2 also has a guide wire inlet and a balloon filling port (not shown in the figure), which have the same structure and function as the conventional balloon, and will not be repeated here.

[0036] The drug balloon 100 is obtained by coating a nifedipine coating on a common clinical balloon, and the coating method is as follows:

[0037] Take 10 nifedipine tablets (total nifedipine 300 mg), remove the coating and grind them into powder; then place the powder in a test tube, add 10 ml acetone and 0.5 ml iopromide injection as the drug-carrying matrix, and shake to fully dissolve the drug. Then ultrasonicate for 10 minutes. Since precipitation is quickly generated after adding iopromide injection, the ultrasonicated solution is filtered with a 0.22 μm filter head to obtain a nifedipine mixed solution for spraying.

[0038] Use ultrasonic spraying equipment to spray the balloon body. Set the flow rate of the ultrasonic spraying equipment to 1.515 mm / min. The spraying parameters are set as follows:

[0039] Spraying times Nozzle moving speed Air pressure Speed 10 times 50mm / min 0.02Kpa 250 rpm

[0040] After ultrasonic spraying, it can be observed that the surface of the balloon body 1 and part of the catheter 2 are covered with a yellow coating, namely the nifedipine coating; the solvent has evaporated quickly, and the balloon 100 coated with the balloon coating 3 can be obtained without baking and drying.

[0041] <Comparative Example>

[0042] In this comparative example, other drug ingredients were used to replace nifedipine in the example, thereby preparing drug-loaded balloons with different ingredients.

[0043] Balloon preparation method: The process is basically the same as the embodiment. Select 10 tablets of nitroglycerin (specification: 0.5 mg, Lesheng Pharmaceutical Shijiazhuang Co., Ltd.; total amount 5 mg), 10 tablets of verapamil (specification: 40 mg, Harbin Pharmaceutical Group Sanjin Pharmaceutical Factory Co., Ltd.; total amount 400 mg), and 10 tablets of papaverine hydrochloride (specification: 30 mg, Qinghai Pharmaceutical Co., Ltd., total amount 300 mg), remove the coating and grind them into powder; then place the powder in a test tube, add 10 ml of acetone and 0.5 ml of iopromide injection as the drug-carrying matrix, and shake to fully dissolve the drug. Then ultrasonicate for 10 minutes, filter the ultrasonic solution with a 0.22 μm filter head, and obtain various mixed solutions for spraying. Use ultrasonic spraying equipment to spray the body of the balloon to obtain various coated balloons.

[0044] <Test example>

[0045] This test example is a performance test comparison of the drug-eluting balloon of the embodiment and the comparative example. The specific test process is as follows:

[0046] The commonly used international modeling method was adopted. New Zealand rabbits with high-energy and high-fat diet were selected, and histamine was injected into the femoral artery to construct a vasospasm New Zealand rabbit model. The success of the model was verified by angiography. 40 New Zealand rabbits with successful modeling were selected and randomly divided into 4 groups, 10 in each group; different balloons were used to observe the relief of spasm, and they were divided into nifedipine balloon group, nitroglycerin balloon group, verapamil balloon group, and papaverine hydrochloride balloon group (10 rabbits in each group), and the vasospasm relief time of each group of New Zealand rabbits with vasospasm after the application of different drug balloons was counted.

[0047] Observation indicators: (1) The degree of vascular spasm was evaluated according to the Otawara standard and divided into three levels: no spasm, mild to moderate spasm (diameter reduction within 60%), and severe spasm (diameter reduction of more than 60%). Efficacy evaluation: Spasm relief (residual vascular spasm <30%) or disappearance of vascular spasm was considered effective. (2) The number of vascular spasms that were relieved in <5 minutes and >5 minutes was observed. The results are shown in the following table:

[0048]

[0049]

[0050] As shown in the table above, in actual interventional surgery, every second counts. If it takes more than 5 minutes to relieve vasospasm, it is not very practical. Therefore, the number of cases in which vasospasm is relieved within less than 5 minutes is used as the benchmark to judge the relief effect of the drug-loaded balloon. Judging from the number of cases in which vasospasm is relieved within less than 5 minutes in each group, nifedipine has the best spasm relief effect.

[0051] Functions and Effects of the Embodiments

[0052] In the embodiment of the present invention, since the balloon coating 3 containing nifedipine is coated on the balloon body 1, on the one hand, the nifedipine in the balloon coating can inhibit the excitation-contraction coupling of the blood vessels, dilate the blood vessels at the contacted part of the balloon body, quickly relieve the vascular spasm state, make the balloon easy to pass, and make the subsequent operation go smoothly; on the other hand, nifedipine can also effectively reduce platelet aggregation, prevent thrombosis and atherosclerotic plaque formation, and greatly reduce the occurrence time and incidence of postoperative restenosis. In addition, since it also contains iopromide, it can be used as a contrast agent to make the development of the balloon body more obvious during the operation, which is more conducive to the operation.

Claims

1. A method for preparing a balloon coating, for preparing a nifedipine coating on a balloon, characterized in that: The following steps are involved: Step S1, adding nifedipine and iopromide into an organic solvent according to a mass volume ratio of 30 to 80 mg / ml of nifedipine and 25 to 45 mg / ml of iopromide to obtain a nifedipine mixed solution; Step S2, coating the nifedipine mixed solution on a predetermined portion of the balloon, and after drying, obtaining a nifedipine coating coated on the balloon.

2. The method for preparing the balloon coating according to claim 1, characterized in that: in, The organic solvent is any one of acetone and chloroform or a combination of the two.

3. The method for preparing the balloon coating according to claim 1, characterized in that: in, The iopromide is an aqueous solution, and its specification is 100ml:76.89g.

4. The method for preparing the balloon coating according to claim 1, characterized in that: in, In step S2, the nifedipine solution is sprayed onto a predetermined position of the balloon using an ultrasonic spray device.

5. A drug balloon, characterized in that: include: A balloon and a nifedipine coating coated on the balloon, Wherein, the nifedipine coating is coated on the balloon by the preparation method of the balloon coating according to any one of claims 1 to 4.

6. The drug balloon according to claim 5, characterized in that: in, The balloon comprises a catheter and a balloon body connected to the catheter, and the nifedipine coating is located on the surface of the balloon body.

7. The drug balloon according to claim 6, characterized in that: in, The nifedipine coating is also located on a portion of the surface of the catheter.

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