Spring ring containing blood coagulation promoting absorbable cellosilk and preparation method of spring ring

Abstract

The invention discloses a spring ring containing blood coagulation promoting absorbable fibers. The spring ring comprises a spring ring body and a plurality of blood coagulation promoting absorbable fibers arranged on the spring ring body. The preparation method comprises the following steps: preparing a viscous spinning solution from oxidized regenerated cellulose, filtering, defoaming, and spinning in a spinning machine using a porous spinning nozzle to obtain oxidized regenerated cellulose tows; and then loading the obtained oxidized regenerated cellulose tows on a spring ring body in an equidistant distribution mode. The blood coagulation promoting absorbable cellosilk is a degradable material, blood coagulation can be promoted, physical full embolism can be achieved in cooperation with the spring ring body, blood flow can be better blocked, and the embolism effect is improved. The blood coagulation promoting absorbable cellosilk is loaded on the spring ring body in a 360-degree surrounding fixed clamping or knotting mode, on one hand, the effective embolism size of the spring ring is increased, on the other hand, the risk that the blood coagulation promoting absorbable cellosilk falls off is reduced, and the safety of the blood coagulation promoting absorbable cellosilk spring ring is improved.

Description

Technical Field

[0001] The invention relates to the technical field of medical devices, and in particular to a spring coil containing blood coagulation-promoting absorbable fiber filaments and a preparation method thereof. Background Art

[0002] The coil for embolization is a medical device commonly used in vascular interventional surgery to treat aneurysms and other vascular systems. It has been widely and maturely used in clinical practice, with definite efficacy and good safety. The coil with fiber filaments is a coil system with fiber filaments attached to the bare coil. Studies have shown that the fiber filaments on the coil facilitate the attachment of platelets and other substances in the blood, which can increase the speed of thrombus formation and achieve denser packing for the target lesion. In addition, the coil with fiber filaments can significantly reduce the number of coils required in embolization surgery, while better locking the embolization position, making the surgery safer.

[0003] Nowadays, the fiber materials of fiber coils are often made of common polymer synthetic spinning such as nylon and polyester. However, this non-absorbable polymer synthetic spinning has the following two problems: first, these materials have no clear blood coagulation mechanism, and only theoretically increase the surface area of ​​the coil to improve the embolization efficiency, and the effect is limited; second, the fiber is often physically connected to the coil body, which inevitably has a certain risk of falling off. After the non-absorbable material falls off in the body, it may cause permanent ectopic embolism, which brings certain harm to the human body.

[0004] Therefore, it is of great significance to develop a spring coil containing pro-coagulant absorbable fibers to improve the embolization efficiency and safety of embolization therapy of the spring coil with fibers, and to provide a higher quality spring coil with fibers for clinical vascular interventional embolization.

[0005] After searching the literature of the prior art, it was found that CN115581491A describes a fiber filament loading device, a fiber filament spring coil for embolism and a preparation method thereof. The fiber filament loading device of the present invention includes a device body, on which are provided: at least one fixed position for loading the spring coil, a plurality of winding sites are provided on the fixed position, the winding sites are arranged in sequence along the extension direction of the fixed position, and the winding sites are used to determine the loading position of the fiber filament on the spring coil; and at least one cutting position, which is used to guide the cutting tool to cut and separate the fiber filament wound on the device body to form the fiber filament. Through the regular winding of the fiber filament, the efficient loading of the fiber filament for not less than one spring coil can be achieved, and at the same time, the controllability and stability of the parameters such as the loading site, loading spacing, length, and quantity of the fiber filament can be ensured. CN117344427A discloses an anti-shedding fiber bundle, a fiber filament spring coil and a manufacturing device thereof. The anti-shedding fiber bundle includes: a core wire, which is used to be wound on a spring coil; and multiple strands of fiber filaments, which are fixed on the core wire at intervals, and the distance between adjacent fiber filaments can be designed and adjusted according to actual application requirements to achieve control of the number and density of fiber filaments. Wrapping it on a spring coil obtains an anti-shedding fiber filament spring coil. It solves the drawback that the spring coil fiber filaments are prone to shedding during clinical use, and avoids complications caused by the spring coil fiber filaments shedding to the distal blood vessels or entering the circulatory system; at the same time, it also overcomes the limitations of the number of fiber filament points, the number of single fiber filaments, and the length of the fiber filaments, and realizes the maximization of the function of promoting thrombosis by using the fiber filaments. CN117918921A discloses a spring coil loaded with a procoagulant and a preparation method thereof, which relates to the technical field of blood coagulation, and includes a spring coil body, and the spring coil body is loaded with a hair bundle fiber for loading the procoagulant, and the hair bundle fiber is composed of a hydrophilic material with biocompatibility. The invention has the effect of improving the embolic effect of the spring coil. When the hair bundle fiber uses hydrophilic materials, it can absorb water in the blood and swell within a period of time after the spring coil is output from the blood vessel, thereby increasing the blood concentration and promoting coagulation. Combined with the physical embolization of the spring coil body, it can better block the blood flow and improve the embolic effect.

[0006] However, the above technical solutions all have some limitations to a greater or lesser extent: the technical solutions described in CN115581491A and CN117344427A mainly innovate in the way of fixing the fiber filaments, aiming to improve the fixing strength of the fiber filaments, but the fiber filament materials mentioned in their inventions are still conventional polyethylene terephthalate, polyamide, glycolide-lactide copolymer, polyethylene, etc., and no technical solution is provided to improve blood coagulation and embolization efficiency; CN117918921A provides a method for loading coagulants on fiber bundles to improve blood coagulation efficiency, but the method of loading coagulants on fiber bundles is only physical immersion and freeze-drying, and the binding force between the fiber bundles and the coagulants is weak. At the same time, the fiber bundle material is natural silk fiber, which fails to solve the inherent disadvantages of non-absorbable fiber filaments.

[0007] Based on the limitations of the above-mentioned design, the present invention has developed a spring coil containing pro-coagulant absorbable fibers and a preparation method thereof, which can improve the efficiency of embolization treatment of vascular malformations such as aneurysms and reduce the risk of ectopic embolism caused by fiber detachment, thereby improving the effectiveness and safety of the spring coil in vascular embolization treatment. Summary of the invention

[0008] The purpose of the present invention is to provide a spring coil containing pro-coagulant absorbable fibers and a preparation method thereof. The development of a spring coil containing pro-coagulant absorbable fibers is beneficial to improving the efficiency of embolization treatment of vascular malformations such as aneurysms and reducing the risk of ectopic embolism caused by fiber shedding.

[0009] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0010] The invention provides a spring coil containing blood coagulation promoting absorbable fiber filaments, comprising a spring coil body and a plurality of blood coagulation promoting absorbable fiber filaments arranged on the spring coil body.

[0011] Furthermore, the shape of the spring coil body includes one of a cylindrical spiral shape, a figure 8 shape, a tower shape, and a bird's nest shape;

[0012] The diameter of the secondary coil of the spring coil body is 1 to 45 mm.

[0013] Furthermore, the material of the spring coil body includes one of chromium-nickel-iron alloy, platinum-tungsten alloy, and platinum-gold alloy.

[0014] Furthermore, a plurality of the pro-coagulant absorbable fibers are radially fixed on the entire periphery of the spring coil body.

[0015] Furthermore, 4 to 12 of the pro-coagulant absorbable fibers are arranged around the structural cross section of the spring coil body.

[0016] Furthermore, the length of the blood coagulation promoting absorbable fiber filaments is 10 mm to 50 mm, and the number of the blood coagulation promoting absorbable fiber filaments bundles is 5 to 100.

[0017] Furthermore, the blood coagulation promoting absorbable fiber filaments are degradable materials, and the materials used include one or more of oxidized regenerated cellulose, chitosan, collagen, gelatin, and alginate.

[0018] This embodiment discloses a method for preparing a spring coil containing blood coagulation-promoting absorbable fiber filaments, comprising the following steps:

[0019] Firstly, the Cr-Ni-Fe alloy wire is subjected to two spring winding heat treatments to obtain a secondary spring coil with a cylindrical spiral structure;

[0020] Then, the oxidized regenerated cellulose powder is dispersed and dissolved in a sodium hydroxide solution to prepare a viscous spinning solution, which is filtered and degassed before entering a spinning machine using a porous spinneret for spinning. The resulting spun fibers are reacted in an acid bath oxidation reactor, and the resulting fiber filaments are subsequently cut to obtain oxidized regenerated cellulose tows.

[0021] Next, the oxidized regenerated cellulose tow obtained above is loaded on the spring coil body in an equidistantly distributed manner in a double-layer single-knotted knotting manner;

[0022] Finally, the obtained embolic spring coil containing the blood coagulation promoting fibrin is ultrasonically cleaned, dried, packaged and sterilized to achieve a clinically usable state.

[0023] Compared with the prior art, the beneficial technical effects of the present invention are:

[0024] 1. The absorbable fiber filaments that promote blood coagulation are biodegradable materials. They can increase the filling volume and provide attachment sites for platelets, fibrinogen and other substances in the blood within a period of time after the coil is output from the blood vessel, thereby promoting blood coagulation. Combined with the physical embolization of the coil itself, it can better block the blood flow and improve the embolization effect.

[0025] 2. The degradable and absorbable properties of the pro-coagulant absorbable fiber filaments also reduce the risk of permanent ectopic embolism caused by fiber shedding, and improve the safety of the pro-coagulant absorbable fiber filament coils.

[0026] 3. The blood-clotting-promoting absorbable fibers have the characteristics of natural fibers, are relatively easy to obtain, and are safer for human use.

[0027] 4. The blood coagulation-promoting absorbable fiber filaments are loaded on the spring coil body in a 360° fixed clamping or knotting manner, which increases the effective embolic volume of the spring coil on the one hand, and reduces the risk of the blood coagulation-promoting absorbable fiber filaments falling off on the other hand, thereby improving the safety of the blood coagulation-promoting absorbable fiber filament spring coil. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The present invention will be further described below in conjunction with the accompanying drawings.

[0029] Figure 1 It is a schematic diagram of the use structure of the embolic coil containing the blood coagulation promoting absorbable fiber filaments in the present invention;

[0030] Figure 2 Schematic diagram of the knotting site of the blood coagulation promoting absorbable fiber filament in Example 1;

[0031] Figure 3 Schematic diagram of the knotting site of the blood coagulation-promoting absorbable fiber filaments in Example 2;

[0032] Figure 4 Schematic diagram of the knotting site of the blood coagulation promoting absorbable fiber filament in Example 3;

[0033] Figure 5 It is an enlarged schematic diagram of the specific knotted structure of the blood-promoting absorbable fiber filaments.

[0034] Reference numerals:

[0035] 1. Spring coil body; 2. Blood coagulation promoting absorbable fiber. DETAILED DESCRIPTION

[0036] This embodiment discloses an embolic spring coil containing blood coagulation-promoting absorbable fibers, including a spring coil body and blood coagulation-promoting absorbable fibers loaded on the spring coil body.

[0037] The material of the spring coil body is chromium-nickel-iron alloy, platinum-tungsten alloy, platinum-gold alloy, etc., and its three-dimensional structure is cylindrical spiral, figure 8, tower, bird's nest, etc., and the diameter of its secondary coil is 1 to 45 mm; wherein the secondary coil of the spring coil body 1 refers to the diameter of the spring coil after looping, which is the most basic and important aspect of selecting the spring coil. The diameter of the spring coil is usually regarded as the first value of the spring coil specification, which is directly related to the adaptability of the spring coil to the aneurysm diameter. For non-spherical aneurysms, the diameter of the first spring coil can be roughly set to the average length of the three axes of the aneurysm, and the diameter of subsequent spring coils should be reduced successively to ensure that the spring coil filled in the aneurysm can adapt to the shape of the aneurysm, thereby achieving the effect of embolization.

[0038] The material of the blood coagulation-promoting absorbable fiber filaments includes one or more of oxidized regenerated cellulose, chitosan, collagen, gelatin, and alginate. The blood coagulation-promoting absorbable fiber filaments are fixed on the spring coil body in a 360° surrounding manner, and the number of fixing sites can be 4 to 12, wherein the fixing sites are loaded on the spring coil body in 360° equal parts, and the specific installation method is clamping, single knotting, double-layer single knotting, etc.

[0039] The length of the pro-coagulant absorbable fiber is 10mm-50mm, and the bundle of the pro-coagulant absorbable fiber is 5-100 strands / bundle. The pro-coagulant absorbable fiber can provide attachment sites for platelets, fibrinogen and other substances in the blood for a period of time after the coil is output from the blood vessel, thereby promoting coagulation. The coil body and the pro-coagulant absorbable fiber form a full embolism, which improves the embolism effect. At the same time, because the pro-coagulant absorbable fiber is degradable and absorbable, the risk of permanent ectopic embolism caused by the shedding of the fiber is reduced, and the safety of the coil containing the fiber is improved. In addition, the double-layer single knot knotting method reduces the risk of the pro-coagulant absorbable fiber shedding.

[0040] In order to verify the practical effect of the present invention, the following embodiments are also made:

[0041] Example 1

[0042] The spring coil body used is made of chromium-nickel-iron alloy, the three-dimensional structure is a cylindrical spiral type, and the diameter of the secondary coil is 10mm.

[0043] The blood coagulation promoting absorbable fiber filaments used are made of oxidized regenerated cellulose.

[0044] And design it through the following steps:

[0045] S1, a chromium-nickel-iron alloy wire with a diameter of 0.0004 inches, is subjected to two spring winding heat treatments, the first metal core shaft diameter is 0.0381 mm (0.0015 inches), and the second metal core shaft diameter is 10 mm, to obtain a secondary spring coil with a three-dimensional structure of a cylindrical spiral.

[0046] S2. The oxidized regenerated cellulose powder is dispersed and dissolved in a 5% sodium hydroxide solution to prepare a viscous spinning solution with a viscosity of 120 Pa.s. After filtering and degassing, the solution is sent to a spinning machine using a porous spinneret for spinning. The resulting spun fibers are reacted in an acid bath oxidation reactor for 30 minutes. The resulting fiber filaments are then cut to obtain oxidized regenerated cellulose bundles with a length of 30 mm and 70 fibers / bundle.

[0047] S3. The oxidized regenerated cellulose tow obtained in S2 is loaded onto the spring coil body in a double-layer single-knotted manner in an equidistant distribution manner of 4 sites / 360°.

[0048] S4. The embolic spring coil containing the procoagulant fibril obtained in S3 is ultrasonically cleaned, dried, packaged and sterilized to achieve clinical usability.

[0049] Example 2

[0050] The same method as in Example 1 was used, except that the number of knotting sites of the oxidized regenerated cellulose was 8 sites / 360°.

[0051] Example 3

[0052] The same method as in Example 1 was used, except that the number of knotting sites of the oxidized regenerated cellulose was 12 sites / 360°.

[0053] Example 4

[0054] The same method as in Example 1 was used, except that the oxidized regenerated cellulose was cut to 10 mm.

[0055] Example 5

[0056] The same method as in Example 1 was used, except that the oxidized regenerated cellulose was cut to 50 mm.

[0057] Example 6

[0058] The same method as in Example 1 was used, except that the number of oxidized regenerated cellulose tows was 40 per tow.

[0059] Example 7

[0060] The same method as in Example 1 was used, except that the number of oxidized regenerated cellulose tows was 100 per tow.

[0061] The embolic coils containing procoagulant absorbable fibers prepared in the above seven embodiments were subjected to an in vitro simulated coagulation experiment using plasma and a catheter. The drug-loaded coil was delivered to a glass tube in 37°C water via a catheter. Fresh plasma was poured into the glass tube to simulate human blood vessels. The plasma coagulation time was recorded. A blank control group was also set up. The results are shown in Table 1.

[0062] Table 1: Results of in vitro simulated coagulation experiment

[0063]

[0064] The blank case is the time for the plasma to coagulate naturally in a glass test tube, and Examples 1-7 are compared with it;

[0065] Experiments show that when the embolic coil is loaded with oxidized regenerated cellulose with a length of 10 mm to 50 mm and 40 to 100 fibers per bundle, the plasma coagulation time is greatly shortened and the plasma embolization effect is significantly improved; therefore, the embolic coil containing pro-coagulant absorbable fibers prepared by this method can achieve the effect of efficient embolization.

[0066] Examples 1-7 use different bundle lengths, numbers of strands and bundle knotting sites to produce embolic spring coils containing pro-coagulant absorbable fibers. The plasma coagulation time shows that when the number of oxidized regenerated cellulose bundles is 70 strands / bundle, the bundle length is 30 mm, and the number of bundle knotting sites is 8 / 360°, that is, Example 2 has the shortest plasma coagulation time and the best embolic effect.

[0067] Take oxidized regenerated cellulose for in vitro degradation study, cut the sample into 0.5cm-1cm length, place it in a vacuum drying oven and dry it for 24h, the temperature is set to 37℃±1℃; weigh 5 test period samples, do 3 parallel tests in each test period, and 1 blank control, weigh about 0.1g sample in each parallel test, accurately weigh it with an electronic balance (accurate to 1% of the total mass), and record the initial mass m0. Put the weighed sample in a syringe bottle, add Sorensen phosphate buffer at 10:1 {buffer volume (mL): sample mass (g)} (make sure the sample is completely immersed in the buffer). Set up 5 test cycles to measure the change in sample mass: 4 days, 8 days, 12 days, 16 days, and the last test period is when the oxidized regenerated cellulose loses its integrity.

[0068] Take a filter membrane (0.4 μm) and place it in a vacuum drying oven at 37°C ± 1°C. Vacuum dry it to constant weight. Use an electronic balance to weigh the mass of the filter membrane (accurate to 1% of the total mass) and record it as mass m2 for later use.

[0069] Take out the samples from the test cycle, put the filter membrane with constant weight into the funnel (diameter 40mm), pour the buffer solution containing the degraded sample into the filter membrane for filtration, and collect the filtrate for degradation product analysis; rinse the vial with analytical water until there is no sample and fragments in the vial, and wash the sample and fragments 3 times with analytical water.

[0070] Place the collected samples and fragments (make sure the samples and fragments are collected completely) and the filter membrane into a vacuum drying oven, set the temperature to 37°C ± 1°C, vacuum dry for 24 hours, take out the completely dried samples, weigh them with an electronic balance (accurate to 1% of the total mass), and record them as mass m1.

[0071] The difference between the initial mass of the test sample and the mass of the test sample after degradation is calculated, and the mass change (degradation rate) ⊿m (%) of the sample is obtained by the ratio of the difference to the initial mass of the sample.

[0072] ⊿m(%)=m0-(m1-m2) / m0×100%

[0073] Table 2: In vitro degradation mass loss rate of absorbable regenerated cellulose

[0074] Test cycle (days) Quality loss rate 4 10.38％ 8 25.49％ 12 50.62％ 16 85.17％ 21 100.00％

[0075] As shown in Table 2, the complete degradation time of absorbable regenerated cellulose in vitro is 21 days.

[0076] The above embodiments are only descriptions of the preferred methods of the invention, and are not intended to limit the scope of the invention. Without departing from the design spirit of the invention, various modifications and improvements made to the technical solutions of the invention by ordinary technicians in this field should fall within the protection scope of the claims of the invention.

Claims

1. A spring coil containing blood coagulation promoting absorbable fibers, characterized in that: The invention comprises a spring coil body and a plurality of blood coagulation-promoting absorbable fibers arranged on the spring coil body.

2. The spring coil containing the blood coagulation promoting absorbable fiber according to claim 1, characterized in that: The shape of the spring coil body includes one of a cylindrical spiral shape, a figure 8 shape, a tower shape, and a bird's nest shape; The diameter of the secondary coil of the spring coil body is 1 to 45 mm.

3. The spring coil containing the blood coagulation promoting absorbable fiber according to claim 2, characterized in that: The material of the spring coil body includes one of chromium-nickel-iron alloy, platinum-tungsten alloy and platinum-gold alloy.

4. The spring coil containing the blood coagulation promoting absorbable fiber according to claim 3, characterized in that: A plurality of the procoagulant absorbable fibers are radially fixed on the entire periphery of the coil body.

5. The spring coil containing the blood coagulation promoting absorbable fiber according to claim 4, characterized in that: 4 to 12 blood coagulation-promoting absorbable fibers are arranged around the structural cross section of the spring coil body.

6. The spring coil containing the blood coagulation promoting absorbable fiber according to claim 5, characterized in that: The length of the blood coagulation promoting absorbable fiber thread is 10 mm to 50 mm, and the number of the blood coagulation promoting absorbable fiber thread bundles is 5 to 100.

7. The spring coil containing the blood coagulation promoting absorbable fiber according to claim 6, characterized in that: The blood coagulation promoting absorbable fiber filaments are degradable materials, and the materials used include one or more of oxidized regenerated cellulose, chitosan, collagen, gelatin, and alginate.

8. A method for preparing a spring coil containing a blood coagulation-promoting absorbable fiber, according to any one of claims 1 to 7, characterized in that: The steps include: Firstly, the Cr-Ni-Fe alloy wire is subjected to two spring winding heat treatments to obtain a secondary spring coil with a cylindrical spiral structure; Then, the oxidized regenerated cellulose powder is dispersed and dissolved in a sodium hydroxide solution to prepare a viscous spinning solution, which is filtered and degassed before entering a spinning machine using a porous spinneret for spinning. The resulting spun fibers are reacted in an acid bath oxidation reactor, and the resulting fiber filaments are subsequently cut to obtain oxidized regenerated cellulose tows. Next, the oxidized regenerated cellulose tow obtained above is loaded onto the spring coil body in an equidistantly distributed manner in a double-layer single-knotted knotting manner; Finally, the obtained embolic spring coil containing the pro-coagulant fibril is ultrasonically cleaned, dried, packaged and sterilized to achieve a clinically usable state.

Images