Rapamycin-loaded calcium alginate puncture needle based on local constraint effect medicine

Abstract

The invention relates to a rapamycin-loaded calcium alginate puncture needle based on medicine with a local restraint effect, which comprises a needle main body and a plurality of drainage needle heads connected and led out through a connector by adopting a drainage tube, and the outer surface and the inner surface of each drainage needle head are both provided with a rapamycin-loaded calcium alginate coating. According to the method for determining the number of the drainage needle heads, segmentation is carried out according to different ages, and the number value range is obtained according to a preset calculation formula. According to the puncture needle, local puncture is achieved through the multiple drainage needles, the inner coating is fused through upstream blood to compensate loss of the outer coating, medicine distribution is uniform, and the distribution range is controllable.

Description

Technical Field

[0001] This invention relates to a rapamycin-loaded calcium alginate puncture needle, and more specifically, to a drug-coated puncture needle for treating early-stage stenosis of arteriovenous fistulas by administering medication to the vessel wall via a puncture needle during dialysis in patients undergoing hemodialysis for arteriovenous fistulas. This invention belongs to the field of medical device components. Background Technology

[0002] With the increasing prevalence of end-stage renal disease (ESRD), nearly 4 million ESRD patients worldwide receive renal replacement therapy. Hemodialysis is one of the main methods of renal replacement therapy, and autogenous arteriovenous fistula is the preferred vascular access for hemodialysis patients, serving as a "lifeline" for ESRD patients.

[0003] However, the 1-year patency rate of AVF is only 63%, and the patency rate drops to 40% after 2 years [3]. Venous neointimal hyperplasia (VNH) causes AVF stenosis and secondary thrombosis, eventually leading to arteriovenous fistula occlusion, which is the main cause of AVF failure. At present, the clinical intervention methods for AVF failure are all treatments after AVF failure, such as reoperation, balloon dilation, vascular stenting, etc., and there are problems such as depletion of vascular resources, high cost, and restenosis. At present, there is still a lack of treatment methods for the early stage of AVF stenosis. Therefore, finding treatment methods for the early stage of AVF stenosis is expected to break through the clinical bottleneck of AVF failure prevention and treatment.

[0004] During clinical dialysis, part of the AVF puncture needle comes into contact with the arteriovenous fistula wall, and the puncture needle remains in the blood vessel for about 4 hours. This provides the possibility of early treatment of AVF stenosis by loading drugs onto the surface of the hemostatic needle coating and administering the drugs locally to the blood vessel wall during dialysis.

[0005] Rapamycin is currently widely used clinically to prevent restenosis of blood vessels, such as in drug-eluting balloons for arteriovenous fistulas and coronary stents. Calcium alginate-coated puncture needles loaded with rapamycin hold promise for treating early AVF stenosis.

[0006] However, due to blood flow, some medications cannot reach the local area in a timely manner and instead travel to other parts of the body with the bloodstream. Therefore, how to enhance the localization of drug action is a challenge. At the same time, how to compensate for drug loss due to friction when the puncture needle enters the skin is also a problem. Summary of the Invention

[0007] 1. The core points of this invention

[0008] First, a compensating coating is added to the inner surface of the puncture needle.

[0009] Secondly, a multi-headed drainage needle is drawn out from the puncture needle and inserted into the surrounding area to allow the drained blood to flow back into the surrounding area, thus achieving the effect of collecting the lost medication and allowing it to be applied locally again.

[0010] Third, through experiments, the amount of drug lost within a specified time is detected, and the number of heads is set accordingly.

[0011] 2. Main body of the invention technology

[0012] This invention provides a rapamycin-loaded calcium alginate puncture needle based on a locally restraining drug, comprising a needle body and multiple drainage needles connected via a connector and a drainage tube. Both the outer and inner surfaces of the drainage needles are coated with rapamycin-loaded calcium alginate. The method for determining the number of the multiple drainage needles includes the following steps: S1 recruits volunteers, who are divided into different age groups. There are multiple volunteers in each age group. The connector is connected to only one drainage needle. The puncture needle is inserted into the skin of different age groups to reach the target area. S2 collects the blood drawn from the drainage needle for 3-5 seconds; S3 uses high-performance liquid chromatography (HPLC) to detect the content of rapamycin in the extracted blood. Let the total local effect of the target be... Set threshold This is the minimum dose for a single local application. To detect the corresponding content extracted by high performance liquid chromatography, the dosage-effect relationship of the drug can be determined. Then the lower limit of the number Must meet In this case, The lower limit of the actual number As the integer operator, the value range for multiple drainage needles is... To specify the maximum number; S4 incorporates the calculation method for age groups, assuming there is a lower limit to the average number of items for each age group. Then the range of values ​​for each drainage needle in this age group is: Then the final acceptable range is .

[0013] Optionally, the connector includes a plurality of drainage needle connection positions and a plug corresponding to each connection position. When a connection position is idle and not connected to a drainage tube for connecting a drainage needle, the connection position is filled with the plug, and the plug is removed when connecting.

[0014] Preferably, a flexible band connects the plug cap to the side wall of the connector. This allows the plug cap to be connected to the connector, and when the plug cap is removed, the flexible band connects the plug cap to the side of the connector, eliminating the need for additional plug cap storage.

[0015] Preferably, the length of the drainage needle is 1-2 cm.

[0016] The aforementioned rapamycin-loaded calcium alginate puncture needle based on a locally restraining drug also includes a dialysis tube connected to a connector. The insertion point of the needle body is upstream of the blood flow, while the insertion point of the drainage tube is at the site of action, located downstream of the blood flow.

[0017] Therefore, instead of simply loading a coating onto the puncture needle, a multi-headed drainage needle with both inner and outer coatings is used to constrain the medication locally, solving the problem of drug loss at the site when using a single puncture needle. Multiple drainage needles are inserted locally, and the upstream blood flow washes away the inner coating to compensate for the loss of the outer coating, allowing the medication to reach multiple discrete insertion points in the local area, resulting in uniform drug distribution and a controllable distribution range. Attached Figure Description

[0018] Figure 1 A schematic diagram of the structure of a rapamycin-loaded calcium alginate puncture needle based on a drug with local restraint effect in an embodiment of the present invention; Figure 2 for Figure 1 Enlarged view of section A circled by the drainage needle; Figure 3 Diagram showing the insertion state of the rapamycin-loaded calcium alginate puncture needle based on the local constraint effect drug of the present invention. Detailed Implementation

[0019] Example 1

[0020] Figure 1 This is a schematic diagram of a rapamycin-loaded calcium alginate puncture needle based on localized restraint drug action. It includes a single needle body connected to a connector. The connector includes five plugs connected to the sides of the connector by flexible bands. Two plugs are not removed in the diagram; the other three are connected to three drainage tubes, each connected to a 2cm long drainage needle. Part A of the drainage needle is circled in the diagram. Figure 2 The enlarged view shows the outer and inner surface coatings. The connector also connects a dialysis tubing to the dialysis equipment.

[0021] like Figure 3 As shown, the needle body pierces upstream of the blood flow direction in the blood vessel, and three drainage needles are inserted around the downstream area of ​​action. The upstream blood flows into the three drainage tubes through the puncture needles and continues into the three drainage needles, melting the inner coating and confining it to the local area of ​​action, while the outer coating is activated by the insertion point of the drainage needles.

[0022] The number of three drainage tubes was obtained using the following method: S1: Recruit volunteers and divide them into age groups: 0-14 years old, 15-24 years old, 24-40 years old, 41-60 years old, and over 60 years old. There are multiple volunteers in each age group. The connector is connected to only one drainage needle. The puncture needle is inserted into the skin of different age groups to reach the target area. S2: Collect the blood drawn from one drainage needle for 3.5 seconds; S3: The content of rapamycin in the extracted blood was detected by high performance liquid chromatography (HPLC). Let the total local effect of the target be... Set threshold This is the minimum dose for a single local application. High-performance liquid chromatography (HPLC) detects the corresponding content in the expelled fluid, and the drug dosage-effect relationship can be determined from this. Then the lower limit of the number Must meet In this case, The lower limit of the actual number As the integer operator, the value range for multiple drainage needles is... To specify the maximum number; S4: Incorporate age group calculation methods, assuming a lower limit for the average number of items for each age group. Then the range of values ​​for each drainage needle in this age group is: Then the final acceptable range is .

[0023] Example 2 This embodiment is in Figure 3 In cases with additional drainage needles, the connector has four drainage needle connection positions, each equipped with a plug, which is connected to the connector sidewall via a flexible band. The length of the drainage needle is 1.5 cm.

[0024] The number of multiple drainage needles is determined by the following method: S1: Recruit volunteers and divide them into age groups of 24-40 years old. There are multiple volunteers in each age group. The connector is connected to only one drainage needle. The puncture needle is inserted into the skin of the volunteer in this age group to reach the target area. S2: Collect the blood drawn from one of the drainage needles for 4 seconds; S3: The content of rapamycin in the extracted blood is detected by high performance liquid chromatography (HPLC). For the specific formula, please refer to step S3 of Example 1.

[0025] S4: Calculate the lower limit N of the average number of items for the 24-40 age group. avg Therefore, the range of values ​​for the drainage needle in this age group is [N]. avg, N maxIf ], then the final possible range is [max(N lower N avg ),N max] N_max specifies the maximum number of possible values ​​for multiple drainage needles.

[0026] This embodiment uses four drainage needles. The main body of the needle is inserted upstream of the blood flow, and the four drainage needles are inserted downstream around the target area.

[0027] Example 3 In this embodiment, the connector is designed with five drainage needle connection positions, and the length of the drainage needle is set to 1.0 cm. It is suitable for children aged 0-14 years. The number of drainage needles is determined by the following method: S1: Recruit volunteers and divide them into age groups of 0-14 years old. There are multiple volunteers in each age group. The connector is connected to only one drainage needle. The puncture needle is inserted into the skin of the volunteer in that age group to reach the target area. S2: Collect the blood drawn from one of the drainage needles for 3 seconds; S3: The content of rapamycin in the extracted blood is detected by high performance liquid chromatography (HPLC). For the specific formula, please refer to step S3 of Example 1. S4 calculates the lower limit of the average number of items for the 0-14 age group. avg Therefore, the range of values ​​for the drainage needle in this age group is [N]. avg, N max If ], then the final possible range is [max(N lower N avg ),N max] N_max specifies the maximum number of possible values ​​for multiple drainage needles.

[0028] This embodiment can use two drainage needles. The needle body is placed upstream of the blood flow, and the two drainage needles are placed downstream at the site of action.

[0029] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A rapamycin-loaded calcium alginate puncture needle based on a drug with local restraint effect, characterized in that, The device includes a needle body and multiple drainage needles connected via a connector and a drainage tube. Both the outer and inner surfaces of each drainage needle are coated with calcium alginate containing rapamycin. The method for determining the number of drainage needles includes the following steps: S1 recruits volunteers, who are divided into different age groups. There are multiple volunteers in each age group. The connector is connected to only one drainage needle. The puncture needle is inserted into the skin of different age groups to reach the target area. S2 collects the blood drawn from the drainage needle for 3-5 seconds; S3 uses high-performance liquid chromatography (HPLC) to detect the content of rapamycin in the extracted blood. Let the total local effect of the target be... Set threshold This is the minimum dose for a single local application. To detect the corresponding content extracted by high performance liquid chromatography, the dosage-effect relationship of the drug can be determined. Then the lower limit of the number Must meet In this case, The lower limit of the actual number As the integer operator, the value range for multiple drainage needles is... To specify the maximum number; S4 incorporates the calculation method for age groups, assuming there is a lower limit to the average number of items for each age group. Then the range of values ​​for each drainage needle in this age group is: Then the final acceptable range is .

2. The puncture needle according to claim 1, characterized in that, The connector includes multiple drainage needle connection positions and a plug corresponding to each connection position. When a connection position is idle and not connected to a drainage tube to connect a drainage needle, the connection position is filled with the plug, and the plug is removed when connecting.

3. The puncture needle according to claim 1, characterized in that, A flexible strip connects the plug to the side wall of the connector.

4. The puncture needle according to claim 1, characterized in that, The length of the drainage needle is 1-2 cm.

5. The puncture needle according to claim 1, characterized in that, The puncture needle also includes a dialysis tube connected to the connector. The insertion point of the needle body is upstream of the blood flow, while the insertion point of the drainage tube is at the point of action, located downstream of the blood flow.

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