A method of making an in situ hemostatic needle

Abstract

The application discloses a preparation method of an in-situ hemostatic needle head, which comprises the following steps: forming a hemostatic coating by the polyelectrolyte interface complexation of a positively charged polyelectrolyte solution and a negatively charged polyelectrolyte solution, and coating the hemostatic coating on the surface of the needle head; and obtaining the in-situ hemostatic needle head after waiting for the hemostatic coating to dry; the raw material for preparing the hemostatic coating of the application does not use a crosslinking agent, so that the hemostatic coating prepared by the application will not produce crosslinking agent residues in the use process, thereby avoiding symptoms such as wound inflammation and allergy, and not affecting the recovery of the wound and other complications; in addition, the two polyelectrolyte solutions with opposite charges of the application will form gel fibers under the interface complexation of the two polyelectrolytes after being in contact with each other, and the hemostatic coating can be plasticized in the subsequent steps, so that the hemostatic needle can be used in different scenes, and the effect of plugging and hemostasis is improved.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a method for preparing an in-situ hemostatic needle. Background Technology

[0002] Currently, in clinical medicine, venous, arterial, and tissue punctures are commonly used diagnostic and treatment methods for blood collection and drainage, organ biopsies, etc. Punctures often cause various types of bleeding. Although most bleeding caused by punctures in clinical practice does not have a significant impact on the patient, to avoid complications such as infection, patients or nurses usually need to perform hemostasis through bandaging, pressure bandaging, digital pressure, tourniquets, etc., which is labor-intensive and cumbersome. Furthermore, for patients with coagulation disorders, such as hemophilia or those undergoing anticoagulation therapy, the puncture process may cause severe bleeding.

[0003] In the prior art, Chinese patent CN109330654B discloses a hemostatic needle, its preparation method, and its application. The hemostatic needle includes a needle tip and a hemostatic coating applied to the outer peripheral surface of the needle tip. The hemostatic coating is a non-toxic, cross-linked polymer that swells upon contact with a solvent and detaches from the outer peripheral surface of the needle tip. Using the hemostatic needle prepared according to this invention, when blood vessels and organs are punctured, the coating remains at the puncture site after withdrawal, blocking the puncture hole, thereby achieving simultaneous hemostasis. However, this application uses a cross-linked polymer as a raw material. Cross-linked polymers are prone to producing cross-linking agent residues, which can easily cause wound inflammation and allergic reactions, severely hindering wound healing and potentially leading to other complications. Furthermore, this hemostatic coating is not malleable and its morphology cannot be controlled; therefore, it cannot be used in scenarios with large blood volumes or high blood pressure, such as arterial puncture.

[0004] In the prior art, Chinese patent CN113180788A discloses a method for preparing a hemostatic needle, which forms a hemostatic coating on the surface of the metal needle tip by electrophoretic deposition. The material of the hemostatic coating is a composite material of polymeric and inorganic materials. The polymeric material is any one or more of chitosan, sodium alginate, PLGA, cellulose, and silk fibroin, and the inorganic material is any one or more of bioglass, bioceramics, and hydroxyapatite. However, the preparation method of this application involves immersing the needle tip in an electrophoretic deposition solution to form a hemostatic coating of uniform thickness on the needle tip surface. The drawbacks of this method are as follows: First, because the needle is immersed in the electrophoresis solution, the hemostatic coating may clog the needle hole. Second, although the electrophoresis solution is not easy to precipitate under the action of an electric field, it will still precipitate after a long time, which requires rapid operation and will result in poor connection stability between the prepared hemostatic coating and the needle. Third, the hemostatic coating is not plastic and its morphology cannot be controlled, so it cannot be used in scenarios with large blood volume and high blood pressure, such as arterial puncture. Summary of the Invention

[0005] To address the technical problems of existing hemostatic coatings easily causing symptoms such as inflammation and allergies, and the inability to control the morphology of hemostatic coatings, this invention provides a method for preparing an in-situ hemostatic needle.

[0006] The technical solution adopted in this invention is: a method for preparing an in-situ hemostatic needle, which involves forming a hemostatic coating by complexing a positively charged polyelectrolyte solution and a negatively charged polyelectrolyte solution at the polyelectrolyte interface, applying the hemostatic coating to the needle surface, and obtaining the in-situ hemostatic needle after the hemostatic coating dries. It can be seen that this invention eliminates the use of cross-linking agents in the raw materials for preparing the hemostatic coating. Therefore, the prepared hemostatic coating will not produce cross-linking agent residues during use, thereby avoiding wound inflammation and allergic reactions, and will not affect wound healing or other complications. Moreover, the raw materials used in this invention are quite ingenious, employing two polyelectrolytes with opposite charges. The hemostatic coating is formed by the interfacial complexation of the polyelectrolytes. When the needle with the hemostatic coating comes into contact with blood, tissue fluid, or other liquids, it undergoes a phase transition from a solid to a gel state, causing the hemostatic coating to separate from the needle surface. It also exhibits tissue adhesion, which is beneficial for sealing puncture wounds, achieving the purpose of sealing the puncture hole, promoting coagulation at the tissue damage site, and preventing infection.

[0007] Furthermore, the specific steps are as follows:

[0008] S1 Addition: Add a positively charged polyelectrolyte solution to the container, and then add a negatively charged polyelectrolyte solution to the adjacent position next to the positively charged polyelectrolyte solution, ensuring that the negatively charged polyelectrolyte solution is in contact with the positively charged polyelectrolyte solution.

[0009] S2 complexation: Positively charged polyelectrolyte solutions and negatively charged polyelectrolyte solutions form gel fiber filaments at the interface of the two polyelectrolytes through complexation at the polyelectrolyte interface.

[0010] S3 winding: The gel fiber filaments from step S2 are wound around the needle tip in a certain shape to form a hemostatic coating;

[0011] S4 Drying: The hemostatic coating in step S3 is dried to obtain the in-situ hemostatic needle.

[0012] The container used in step S1 is a glass vessel to avoid interference between the polyelectrolyte and the container. In step S2, during the complexation process, either a positively charged polyelectrolyte solution or a negatively charged polyelectrolyte solution can be added first. Crucially, the two polyelectrolyte solutions must not be mixed; they must be in adjacent contact. Mixing them will result in a white, flocculent precipitate, preventing the formation of an effective hemostatic coating and hindering subsequent shaping of the coating. Only when the two polyelectrolyte solutions with opposite charges are in adjacent contact can gel fibers form through interfacial complexation, enabling subsequent shaping of the hemostatic coating. This allows the hemostatic needle to be used in different scenarios, improving its sealing and hemostatic effect, which is one of the core principles of this invention.

[0013] Furthermore, in step S3, the hemostatic coating is spaced a certain distance from the tip of the needle. This is to prevent the hemostatic coating from clogging the needle hole and affecting the flow of fluid; on the other hand, since the needle needs to be punctured, if the hemostatic coating is wrapped around the entire tip of the needle, it will affect the puncture.

[0014] Furthermore, in step S3, the hemostatic coating is spaced 0.2 mm to 10 mm from the needle tip. Based on conventional puncture depth calculations, the distance between the hemostatic coating and the needle tip in this invention is preferably 5 mm to 6 mm.

[0015] Furthermore, in step S3, the gel fiber filaments wound around the needle tip are in one of three shapes: cylindrical, spindle-shaped, or conical. Different shapes can be used for different puncture scenarios. A cylindrical hemostatic coating can be used for ordinary venous punctures, while spindle-shaped and conical shapes can be used for scenarios with large blood volumes and high blood pressure, such as arterial punctures. Because the radial cross-sectional areas of the spindle-shaped and conical shapes are different, when the cross-sectional area of ​​the hemostatic coating inside the artery is larger than that outside the artery, the hemostatic coating's sealing and hemostatic effect is enhanced. Therefore, this invention can be used in scenarios with large blood volumes and high blood pressure.

[0016] Furthermore, in step S3, the winding thickness of the gel fiber filaments is 0.1μm to 400μm. If the thickness is too thick, it will affect the puncture and result in an excessively large puncture wound; if it is too thin, the effect of sealing and hemostasis will be poor. Therefore, the present invention preferably has a thickness of 0.1μm to 400μm.

[0017] Furthermore, in step S4, the drying time for the hemostatic coating is 0.1h to 1.5h, and the drying temperature is 30℃ to 60℃. This allows for slow drying at a low temperature, ensuring both the strength and drying efficiency of the hemostatic coating, while also improving the bonding between the coating and the needle, thus enhancing the stability of their connection. If the drying time is too fast or the temperature is too high, it will increase the brittleness of the hemostatic coating and reduce the bonding strength with the needle.

[0018] Furthermore, the concentration of the positively charged polyelectrolyte is 0.1–10 wt%, and the concentration of the negatively charged polyelectrolyte is 0.1–10 wt%. It can be seen that the concentrations of both polyelectrolytes are relatively low. If the concentration is too high, coarser gel fibers will be formed, making it difficult to control the thickness of the hemostatic coating.

[0019] Furthermore, both positively charged and negatively charged polyelectrolyte solutions possess hemostatic properties, while the positively charged polyelectrolyte solution exhibits anti-infection properties. It can be seen that, in addition to its hemostatic effect, the raw materials used in the hemostatic coating also possess hemostatic properties, further enhancing the hemostatic effect through this dual action. Moreover, the positively charged polyelectrolyte solution's anti-infection properties effectively reduce the risk of infection after puncture, creating favorable conditions for wound healing.

[0020] Furthermore, the positively charged polyelectrolyte is one of quaternized chitosan, chitosan, or chitosan oligosaccharide; the negatively charged polyelectrolyte is one of carboxymethyl cellulose, hyaluronic acid, or sodium alginate.

[0021] The beneficial effects of this invention are:

[0022] 1. The raw materials used in preparing the hemostatic coating of this invention do not contain cross-linking agents. Therefore, the prepared hemostatic coating will not produce cross-linking agent residues during use, thereby avoiding wound inflammation and allergies, and will not affect wound healing or other complications.

[0023] 2. This invention utilizes the interfacial complexation of polyelectrolytes to form a hemostatic coating. When a needle with a hemostatic coating comes into contact with blood, tissue fluid, or other liquids, it will undergo a phase transition from a solid state to a gel state, thereby causing the hemostatic coating to separate from the surface of the needle. It also has tissue adhesion, which is beneficial for sealing the puncture wound, thereby achieving the purpose of sealing the puncture hole, promoting coagulation at the site of tissue damage, and preventing infection.

[0024] 3. In this invention, the two polyelectrolyte solutions with opposite charges will form gel fibers through interfacial complexation after they come into contact with each other. This allows the hemostatic coating to be plasticized in subsequent steps, enabling the hemostatic needle to be used in different scenarios and improving its sealing and hemostasis effect.

[0025] 4. The hemostatic coating of the present invention is spaced a certain distance from the tip of the needle. On the one hand, this is to avoid the hemostatic coating from blocking the needle hole and affecting the flow of liquid; on the other hand, since the needle needs to be punctured, if the hemostatic coating is wrapped around the tip of the needle, it will affect the puncture.

[0026] 5. The present invention uses low-temperature slow drying of the hemostatic coating, which can not only ensure the strength and drying efficiency of the hemostatic coating, but also make the hemostatic coating bond better with the needle and improve the stability of the connection between the two.

[0027] 6. In addition to the effect of sealing and stopping bleeding, the hemostatic coating of the present invention also has the function of coagulation in its raw materials. The dual effect further improves the hemostatic effect. Moreover, the positively charged polyelectrolyte solution has anti-infection properties, which can effectively reduce the risk of infection after puncture and create favorable conditions for wound healing. Attached Figure Description

[0028] Figure 1 This is a schematic diagram illustrating the hemostatic principle of the in-situ hemostatic needle of this invention.

[0029] Figure 2 This is a flowchart of the preparation method of the in-situ hemostatic needle of the present invention.

[0030] Figure 3 This is a schematic diagram of the winding of the gel fiber filaments of the present invention.

[0031] Figure 4 This is a scanning electron microscope image of the in-situ hemostatic needle of the present invention.

[0032] Figure 5 This is a comparative diagram of the in-situ hemostatic needle puncturing the rabbit ear artery according to Embodiment 1 of the present invention. Detailed Implementation

[0033] In the description of this invention, it should be noted that the terms "front", "up", "down", "left", "right", "vertical", "horizontal", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0034] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0035] The invention will be further described below with reference to the accompanying drawings.

[0036] Example 1

[0037] Reference Figure 2 A 1 wt% sodium carboxymethyl cellulose solution was contacted with a 2 wt% quaternized chitosan solution, as per [reference]. Figure 3 Gel fibers were formed at the interface of the two phases using polyelectrolyte complexation technology, and then wound into a cylindrical shape around the syringe needle tip. After drying at 45°C for 0.5 h, an in-situ hemostatic needle tip with coagulation and anti-infection functions was obtained. The hemostatic coating was wound 5 mm from the needle tip, and the coating thickness was 150 μm. (Reference) Figure 4 As can be seen, the hemostatic coating prepared by the present invention has a uniform thickness and a smooth surface.

[0038] Effect verification:

[0039] Animal blood vessels simulate hemostasis

[0040] Using the in-situ hemostatic needle prepared in Practice 1, the hemostatic effect was observed via the rabbit middle ear artery. Using a blank injection needle and a hemostatic / anti-infection needle, the pre-prepared rabbit middle ear artery was punctured. After a period of time, the needle was withdrawn, and bleeding at the injection site was observed. (Refer to...) Figure 5 Observation revealed significant bleeding in the middle ear artery of rabbits after puncture with the blank injection needle, with blood flowing out through the injection site. However, after puncture with the in-situ hemostatic needle prepared in this embodiment, there was no significant bleeding in the middle ear artery of rabbits, demonstrating a clear in-situ hemostasis effect.

[0041] Example 2

[0042] A 1 wt% sodium carboxymethyl cellulose solution was contacted with a 2 wt% quaternized chitosan solution. Gel filaments were formed at the interface using polyelectrolyte complexation technology. These filaments were then wound into a conical shape around the tip of a syringe needle and dried at 45°C for 0.5 h to obtain an in-situ hemostatic needle with coagulation and anti-infection functions. The hemostatic coating was wound 5 mm from the needle tip, with a minimum thickness of 0.1 μm and a maximum thickness of 200 μm.

[0043] Effect verification:

[0044] Animal blood vessels simulate hemostasis

[0045] Using the in-situ hemostatic needle prepared in Embodiment Two, the hemostatic effect was observed through the rabbit middle ear artery. A blank injection needle and a hemostatic / anti-infection needle were used to puncture the pre-prepared rabbit middle ear artery. After a period of time, the needles were withdrawn, and bleeding at the injection site was observed. Observation showed that significant bleeding occurred in the rabbit middle ear artery after puncture with the blank injection needle, with blood flowing out through the injection site. After puncture with the in-situ hemostatic needle prepared in this embodiment, there was no significant bleeding in the rabbit middle ear artery, demonstrating a significant in-situ hemostatic effect.

[0046] Example 3

[0047] A 1 wt% sodium carboxymethyl cellulose solution was contacted with a 2 wt% quaternized chitosan solution. Gel fibers were formed at the interface using polyelectrolyte complexation technology. These fibers were then wound into a spindle shape around the syringe needle tip and dried at 45°C for 0.5 h to obtain an in-situ hemostatic needle with coagulation and anti-infection functions. The hemostatic coating was wound 5 mm from the needle tip, with a minimum thickness of 0.1 μm and a maximum thickness of 200 μm.

[0048] Effect verification:

[0049] Animal blood vessels simulate hemostasis

[0050] Using the in-situ hemostatic needle prepared in Example 3, the hemostatic effect was observed through the rabbit middle ear artery. A blank injection needle and a hemostatic / anti-infection needle were used to puncture the pre-prepared rabbit middle ear artery. After a period of time, the needles were withdrawn, and bleeding at the injection site was observed. Observation showed that the rabbit middle ear artery bled significantly after puncture with the blank injection needle, with blood flowing out through the injection site. After puncture with the in-situ hemostatic needle prepared in this example, there was no significant bleeding in the rabbit middle ear artery, demonstrating a significant in-situ hemostatic effect.

[0051] Example 4

[0052] A 3 wt% sodium carboxymethyl cellulose solution was contacted with a 4 wt% quaternized chitosan solution. Gel filaments were formed at the interface using polyelectrolyte complexation technology. These filaments were then wound into a cylindrical shape around the tip of a syringe needle and dried at 45°C for 0.5 h to obtain an in-situ hemostatic needle with coagulation and anti-infection functions. The hemostatic coating was wound 5 mm from the needle tip, and the coating thickness was 150 μm.

[0053] Effect verification:

[0054] Animal blood vessels simulate hemostasis

[0055] Using the in-situ hemostatic needle prepared in Example 4, the hemostatic effect was observed through the rabbit middle ear artery. A blank injection needle and a hemostatic / anti-infection needle were used to puncture the pre-prepared rabbit middle ear artery. After a period of time, the needles were withdrawn, and bleeding at the injection site was observed. Observation showed that the rabbit middle ear artery bled significantly after puncture with the blank injection needle, with blood flowing out through the injection site. After puncture with the in-situ hemostatic needle prepared in this example, there was no significant bleeding in the rabbit middle ear artery, demonstrating a significant in-situ hemostatic effect.

[0056] Example 5

[0057] Reference Figure 2 A 1 wt% hyaluronic acid solution and a 2 wt% chitosan solution were contacted, and gel fibers were formed at the interface using polyelectrolyte complexation technology. These fibers were then wound into a cylindrical shape around the tip of a syringe needle and dried at 45°C for 0.5 hours to obtain an in-situ hemostatic needle with coagulation and anti-infection functions. The hemostatic coating was wound 5 mm from the needle tip, and the coating thickness was 150 μm.

[0058] Effect verification:

[0059] Animal blood vessels simulate hemostasis

[0060] Using the in-situ hemostatic needle prepared in Example 5, the hemostatic effect was observed through the rabbit middle ear artery. A blank injection needle and a hemostatic / anti-infection needle were used to puncture the pre-prepared rabbit middle ear artery. After a period of time, the needles were withdrawn, and bleeding at the injection site was observed. Observation showed that the rabbit middle ear artery bled significantly after puncture with the blank injection needle, with blood flowing out through the injection site. After puncture with the in-situ hemostatic needle prepared in this example, there was no significant bleeding in the rabbit middle ear artery, demonstrating a significant in-situ hemostatic effect.

[0061] Example 6

[0062] Reference Figure 2 A 1 wt% sodium alginate solution was contacted with a 2 wt% chitosan oligosaccharide solution. At the interface between the two phases, gel fibers were formed using polyelectrolyte complexation technology. These fibers were then wound into a cylindrical shape around the tip of a syringe needle and dried at 45°C for 0.5 h to obtain an in-situ hemostatic needle with coagulation and anti-infection functions. The hemostatic coating was wound 5 mm from the needle tip, and the coating thickness was 150 μm.

[0063] Effect verification:

[0064] Animal blood vessels simulate hemostasis

[0065] Using the in-situ hemostatic needle prepared in Example 6, the hemostatic effect was observed through the rabbit middle ear artery. A blank injection needle and a hemostatic / anti-infection needle were used to puncture the pre-prepared rabbit middle ear artery. After a period of time, the needles were withdrawn, and bleeding at the injection site was observed. Observation showed that significant bleeding occurred in the rabbit middle ear artery after puncture with the blank injection needle, with blood flowing out through the injection site. After puncture with the in-situ hemostatic needle prepared in this example, there was no significant bleeding in the rabbit middle ear artery, demonstrating a significant in-situ hemostatic effect.

[0066] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing an in-situ hemostatic needle, characterized in that, A hemostatic coating is formed by the complexation of a positively charged polyelectrolyte solution and a negatively charged polyelectrolyte solution at the polyelectrolyte interface. This hemostatic coating is then applied to the surface of the needle, and after drying, an in-situ hemostatic needle is obtained. The specific steps are as follows: S1 Addition: Add a positively charged polyelectrolyte solution to the container, and then add a negatively charged polyelectrolyte solution to the adjacent position next to the positively charged polyelectrolyte solution, ensuring that the negatively charged polyelectrolyte solution is in contact with the positively charged polyelectrolyte solution; the two polyelectrolyte solutions remain in adjacent contact without mixing. S2 complexation: Positively charged polyelectrolyte solutions and negatively charged polyelectrolyte solutions form gel fiber filaments at the interface of the two polyelectrolytes through complexation at the polyelectrolyte interface. S3 winding: The gel fiber filaments from step S2 are wound around the needle tip in a certain shape to form a hemostatic coating; S4 Drying: The hemostatic coating in step S3 is dried to obtain the in-situ hemostatic needle. In step S3, the hemostatic coating is spaced 0.2 mm to 10 mm from the tip of the needle; the thickness of the gel fiber winding is 0.1 μm to 400 μm. In step S4, the drying time of the hemostatic coating is 0.1h to 1.5h, and the drying temperature is 30℃ to 60℃. The concentration of the positively charged polyelectrolyte is 0.1–10 wt%, and the concentration of the negatively charged polyelectrolyte is 0.1–10 wt%. The positively charged polyelectrolyte is one of quaternized chitosan, chitosan, or chitosan oligosaccharide; the negatively charged polyelectrolyte is one of carboxymethyl cellulose, hyaluronic acid, or sodium alginate.

2. The method for preparing an in-situ hemostatic needle as described in claim 1, characterized in that, In step S3, the gel fiber filaments wound around the needle tip are in one of the following shapes: cylindrical, spindle-shaped, or conical.

3. The method for preparing an in-situ hemostatic needle as described in claim 1, characterized in that, The positively charged polyelectrolyte solution and the negatively charged polyelectrolyte solution have coagulation function, and the positively charged polyelectrolyte solution has anti-infective properties.

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