Drug loading method for artificial blood vessel and artificial blood vessel

Abstract

Disclosed are a drug loading method for an artificial blood vessel and the artificial blood vessel. An entire artificial blood vessel or end portions thereof, prepared from a biological material, are immersed in a drug loading composition for drug loading treatment, the biological material being a human-derived or animal-derived material, and the drug loading composition being a solution containing paclitaxel. The present invention employs a dimethyl sulfoxide solution containing paclitaxel as the drug loading composition. When performing drug loading treatment on an artificial blood vessel prepared from a biological material, the process only requires immersing the artificial blood vessel into the drug loading composition to perform the drug loading treatment, thereby achieving an excellent drug loading effect. This method is simple and convenient, and can be widely applied to on-site drug loading treatment of artificial blood vessels prepared from biological materials.

Description

Artificial blood vessel drug loading method and artificial blood vessel Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to an artificial blood vessel drug loading method and an artificial blood vessel. Background Art

[0002] Artificial blood vessels are currently widely used clinically, achieving promising results in some areas. However, these applications often involve vascular stenosis or occlusion due to post-implantation proliferation, which can affect vascular function. Therefore, reducing vascular proliferation is a major challenge facing these applications.

[0003] To inhibit angiogenesis, one current solution is to load drugs onto artificial blood vessels, such as forming a drug-loaded coating on the blood vessel wall. However, this method is only applicable to artificial blood vessels made of polymer materials. For artificial blood vessels made of biomaterials, the drug loading effect of existing drug loading methods is often poor, which limits their clinical application.

[0004] Summary of the Invention

[0005] The purpose of the present invention is to provide an artificial blood vessel drug loading method and an artificial blood vessel, so as to solve the problem of poor drug loading effect of artificial blood vessels prepared by using biological materials in application.

[0006] The present invention is achieved through the following technical solutions:

[0007] The artificial blood vessel drug loading method comprises immersing the entire artificial blood vessel or its end portion made of biological material into a drug loading composition for drug loading treatment, wherein the biological material is human or animal-derived material; and the drug loading composition is a solution containing paclitaxel.

[0008] The solvent used in the drug-loaded composition is one or more of dimethyl sulfoxide, N-methylpyrrolidone, and N,N-dimethylacetamide.

[0009] In some embodiments, the concentration of paclitaxel in the drug-loaded composition is 0.1-100 mg / ml.

[0010] In some embodiments, the concentration of paclitaxel in the drug-loaded composition is 0.5-10 mg / ml.

[0011] In some embodiments, the concentration of paclitaxel in the drug-loaded composition is 1-3 mg / ml.

[0012] In some embodiments, the artificial blood vessel is immersed in the drug-loaded composition for no less than 10 seconds.

[0013] In some embodiments, when the drug loading treatment is performed by immersing the end of the artificial blood vessel into the drug-loaded composition, the length of the immersion of the end of the artificial blood vessel is 0.2-25 cm.

[0014] In some embodiments, when the drug loading treatment is performed by immersing the end of the artificial blood vessel into the drug-loaded composition, the length of the immersion of the end of the artificial blood vessel is 0.2-2 cm.

[0015] In some embodiments, the artificial blood vessel is made by winding and sewing bovine pericardium.

[0016] In some embodiments, the bovine pericardium has a thickness of 0.2-0.9 mm.

[0017] In some embodiments, the bovine pericardium is anticalized bovine pericardium.

[0018] In some embodiments, the prepared artificial blood vessel is packaged after being sterilized, and is taken out and trimmed to the desired length and port shape before implantation, and then the artificial blood vessel is treated with a drug-loaded composition.

[0019] In some embodiments, the drug-loaded artificial blood vessel is soaked in sterile physiological saline for 0.5-30 minutes.

[0020] On the other hand, the present invention also provides an artificial blood vessel obtained by the above-mentioned artificial blood vessel drug loading method.

[0021] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0022] The present invention uses a paclitaxel-containing dimethyl sulfoxide solution as the drug-loading composition. When performing drug loading treatment on an artificial blood vessel made of a biomaterial, simply immersing the artificial blood vessel in the drug-loading composition can achieve excellent drug loading results. This simple and convenient operation allows for widespread application in on-site drug loading treatment of artificial blood vessels made of biomaterials. The drug-loading composition can also be made of solvents similar to dimethyl sulfoxide, such as N-methylpyrrolidone, N,N-dimethylacetamide, or mixtures thereof.

[0023] In the drug-loaded composition of the present invention, dimethyl sulfoxide and similar solvents can dissolve paclitaxel well. When an artificial blood vessel made of a biomaterial is immersed in the drug-loaded composition solution, the solution can diffuse well into the biomaterial and form a good distribution in the biomaterial, thereby achieving a good drug-loading effect. In the actual application of the artificial blood vessel, when the artificial blood vessel made of the biomaterial is placed again in an aqueous environment, such as physiological saline, paclitaxel can be rapidly precipitated and adsorbed on tissue fibers inside the biomaterial because it is insoluble in water. After the artificial blood vessel made of the biomaterial is implanted, the paclitaxel can be slowly released from the biomaterial, thereby reducing vascular proliferation, thereby effectively solving the problems existing in the actual application of the artificial blood vessel made of the biomaterial. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings in the embodiments will be briefly introduced below. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0025] FIG1 is a schematic structural diagram of an embodiment of an artificial blood vessel of the present invention.

[0026] Among them: 10. Artificial blood vessels, 20. Sutures. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments.

[0028] Artificial blood vessels made of biomaterials are derived from naturally grown tissues of humans or animals and usually need to be preserved by being immersed in a liquid environment simulating body fluids. Since the liquid environment is rich in water and the material itself is rich in water, the drug loading effect is poor when conventional drug loading methods are used for drug loading.

[0029] In response to the above problems, after extensive research, it was found that when the biomaterial is immersed in a dimethyl sulfoxide solution containing paclitaxel for drug loading treatment, a good drug loading effect can be achieved, which effectively solves the current problems in the drug loading treatment of biomaterial artificial blood vessels and the actual application of artificial blood vessels.

[0030] In some embodiments of the present invention, the artificial blood vessel drug loading method adopted is to immerse the entire artificial blood vessel prepared from biological materials or the end thereof in a drug loading composition for drug loading treatment, wherein the biological material here is human or animal-derived material, such as blood vessels, pericardium, etc.; the drug loading composition used for drug loading treatment is a solution containing paclitaxel, such as a dimethyl sulfoxide solution containing paclitaxel using dimethyl sulfoxide as a solvent.

[0031] The drug-carrying composition herein may also use a solvent similar to dimethyl sulfoxide, such as N-methylpyrrolidone, N,N-dimethylacetamide, etc., or a mixture of the above components.

[0032] In some embodiments, the concentration of paclitaxel in the drug loaded composition is 0.1-100 mg / ml.

[0033] In some embodiments, the concentration of paclitaxel in the drug loaded composition is 0.5-10 mg / ml.

[0034] In some embodiments, the concentration of paclitaxel in the drug loaded composition is 1-3 mg / ml.

[0035] Based on the technical ideas of the present invention and the effect of the drug-loaded composition in drug-loading treatment of artificial blood vessels, it is easy to imagine that the drug-loaded composition and drug-loading method can also be applied to drug-loading treatment of other artificial prostheses prepared with biomaterials.

[0036] In some embodiments, during the drug loading treatment, the artificial blood vessel is immersed in the drug loading composition for at least 10 seconds. Generally, depending on the material and specifications of the artificial blood vessel, as well as the concentration of paclitaxel in the drug loading composition, the immersion time for the drug loading treatment can be 0.5-20 minutes. The drug loading composition solution can also be stirred during the immersion treatment.

[0037] In some embodiments, the artificial blood vessel made of biomaterial can be immersed in its entirety into the drug-loading composition for drug-loading treatment.

[0038] After the entire artificial blood vessel is loaded with the drug-loaded composition solution, the surface can be dried using dry film technology to isolate it from the liquid environment. After sterilization, the artificial blood vessel can be packaged to produce a sterile product. Conventional sterilization methods such as irradiation, ethylene oxide, and chemical liquid sterilization can be used for sterilization.

[0039] In some embodiments, only the ends of a biomaterial artificial blood vessel can be immersed in the drug-loading composition for drug loading. The length of the ends of the artificial blood vessel immersed can be selected from 0.2 to 25 cm, or 0.2 to 2 cm as needed. When only the ends of the artificial blood vessel are immersed in the drug loading treatment, the unimmersed portion of the artificial blood vessel can be treated with physiological saline to keep it moist and prevent dehydration and denaturation. For dry artificial blood vessels, this procedure can be omitted during drug loading.

[0040] In some embodiments, the artificial blood vessel 10 can be made by rolling bovine pericardium into a tube and then sewing it with sutures 20. The prepared artificial blood vessel is shown in FIG1 .

[0041] In some embodiments, the thickness of the bovine pericardium can be selected to be 0.2-0.9 mm, or 0.4-0.8 mm as needed.

[0042] In some embodiments, the bovine pericardium is an anti-calcification treated bovine pericardium. The anti-calcification treatment of the bovine pericardium can be performed by one or more of a decellularization process to remove cell debris and phospholipids in the bovine pericardium (e.g., by using a surfactant wash, freeze-thaw method, etc.), or by chemically blocking free aldehyde groups introduced by glutaraldehyde cross-linking and fixation in the bovine pericardium.

[0043] In some embodiments, the artificial blood vessel prepared by sewing or other means can be sterilized and stored in a bacteria-proof barrier package; before the artificial blood vessel is implanted, the artificial blood vessel is taken out of the sterile package, and sterile scissors are used to trim the artificial blood vessel to the length required for implantation and the end is trimmed to the desired port shape, and then the artificial blood vessel is placed in the drug-loaded composition for drug-loaded treatment.

[0044] In some embodiments, the drug-loaded artificial blood vessel can be soaked in sterile physiological saline for 0.5-30 minutes in preparation for implantation.

[0045] On the other hand, some embodiments also relate to an artificial blood vessel prepared by the above-mentioned artificial blood vessel drug loading method.

[0046] The method for drug loading treatment of an artificial blood vessel in the present invention will be described in detail below with reference to specific embodiments.

[0047] Example 1

[0048] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 0.5 mg / ml;

[0049] The artificial blood vessel prepared by using bovine pericardium material is immersed in the drug-loaded composition solution for 10 minutes. The composition solution is stirred during the immersion period. Then the artificial blood vessel is taken out for implantation.

[0050] Example 2

[0051] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 1 mg / ml;

[0052] The artificial blood vessel prepared by using bovine pericardium material is immersed in the drug-loaded composition solution for 20 minutes. The composition solution is stirred during the immersion period. Then the artificial blood vessel is taken out for implantation.

[0053] Example 3

[0054] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 3 mg / ml;

[0055] The artificial blood vessel prepared by using bovine pericardium material is immersed in the drug-loaded composition solution for 10 minutes. The composition solution is stirred during the immersion period. Then the artificial blood vessel is taken out for implantation.

[0056] Example 4

[0057] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 10 mg / ml;

[0058] The artificial blood vessel prepared by using bovine pericardium material is immersed in the drug-loaded composition solution for 10 minutes. The composition solution is stirred during the immersion period. Then the artificial blood vessel is taken out for implantation.

[0059] Example 5

[0060] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 3 mg / ml;

[0061] The artificial blood vessel prepared by using bovine jugular vein is immersed in the drug-loaded composition solution for 10 minutes. The composition solution is stirred during the immersion period. Then the artificial blood vessel is taken out for implantation.

[0062] Example 6

[0063] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 3 mg / ml;

[0064] The end of an artificial blood vessel made of bovine pericardium material is immersed in the drug-loaded composition solution for 10 minutes. The composition solution is stirred during the immersion period. The artificial blood vessel is then taken out for implantation.

[0065] Example 7

[0066] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 3 mg / ml;

[0067] The artificial blood vessel made of bovine pericardium is taken out of the sterile packaging and trimmed to the required length. The artificial blood vessel is immersed in the drug-loaded composition solution for 10 minutes. The composition solution is stirred during the immersion. The artificial blood vessel is then taken out and immersed in physiological saline for implantation.

[0068] Example 8

[0069] Prepare a dimethyl sulfoxide solution containing paclitaxel at a concentration of 3 mg / ml;

[0070] After taking out the artificial blood vessel made of bovine pericardium from the sterile packaging, trim the two ends to the required port shape, and then immerse the two ends in the drug-loaded composition solution for 10 minutes. Stir the composition solution during the immersion period, then take out the artificial blood vessel and soak it in physiological saline for implantation.

[0071] Example 9

[0072] Prepare a paclitaxel-containing N-methylpyrrolidone solution with a paclitaxel concentration of 3 mg / ml;

[0073] After taking out the artificial blood vessel made of bovine pericardium from the sterile packaging, trim the two ends to the required port shape, immerse the two ends in the drug-loaded composition solution for 10 minutes, stir the composition solution during the immersion, then take out the artificial blood vessel and soak it in physiological saline for implantation.

[0074] Example 10

[0075] Prepare a paclitaxel-containing N,N-dimethylacetamide solution with a paclitaxel concentration of 3 mg / ml;

[0076] After taking out the artificial blood vessel made of bovine pericardium from the sterile packaging, trim the two ends to the required port shape, immerse the two ends in the drug-loaded composition solution for 10 minutes, stir the composition solution during the immersion, then take out the artificial blood vessel and soak it in physiological saline for implantation.

[0077] By testing the drug loading effect of the artificial blood vessels obtained by drug loading treatment, it was found that the artificial blood vessels prepared in the above embodiments can achieve good drug loading effect, and the drug loading amount can meet the use requirement of reducing vascular proliferation after artificial blood vessel implantation, indicating that the drug loading composition and drug loading method can be well applied to the drug loading operation of artificial blood vessels prepared with biomaterials such as bovine pericardium.

[0078] In the description of the present invention, it should be noted that the terms "center", "up", "down", "left", "right", "vertical", "horizontal", "inside", "outside", etc. used to indicate the orientation or position relationship are based on the orientation or position relationship shown in the accompanying drawings, or are the orientation or position relationship in which the product of the invention is usually placed when in use. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, they should not be understood as limiting the present invention.

[0079] Furthermore, the use of terms such as "horizontal" and "vertical" in the description of the present invention does not necessarily imply that the component must be absolutely horizontal or suspended, but rather that it can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal than "vertical" and does not mean that the structure must be completely horizontal, but rather that it can be slightly tilted.

[0080] It should also be noted that, in the description of the present invention, unless otherwise expressly specified or limited, the terms "disposed," "installed," "connected," and "connected" should be understood in a broad sense. For example, they may refer to fixed connections, detachable connections, or integral connections; mechanical connections or electrical connections; direct connections or indirect connections through an intermediate medium; and internal connections between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention in specific contexts.

[0081] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any simple modification or equivalent change made to the above embodiment based on the technical essence of the present invention shall fall within the scope of protection of the present invention.

Claims

1. Method for loading drugs into artificial blood vessels, characterized in that, The artificial blood vessel prepared from biological materials is immersed in the drug-loaded composition as a whole or at its end for drug loading treatment, and the biological material is a human-derived or animal-derived material; the drug-loaded composition is a solution containing paclitaxel.

2. The method for loading drugs into an artificial blood vessel according to claim 1, wherein, The solvent used in the drug-loaded composition is one or more of dimethyl sulfoxide, N-methylpyrrolidone, and N,N-dimethylacetamide.

3. The artificial blood vessel drug loading method according to claim 1 or 2, characterized in that, The concentration of paclitaxel in the drug-loaded composition is 0.1 - 100 mg / ml.

4. The method for loading drugs into an artificial blood vessel according to claim 3, wherein The concentration of paclitaxel in the drug-loaded composition is 0.5 - 10 mg / ml.

5. The method for loading drugs into an artificial blood vessel according to claim 1 or 2, characterized in that, The immersion time of the artificial blood vessel in the drug-loaded composition is not less than 10 s.

6. The method for loading drugs into artificial blood vessels according to claim 1 or 2, characterized in that, When the end of the artificial blood vessel is immersed in the drug-loaded composition for drug loading treatment, the immersed length of the end of the artificial blood vessel is 0.2 - 25 cm.

7. The method for loading a drug into an artificial blood vessel according to claim 6, wherein, When the end of the artificial blood vessel is immersed in the drug-loaded composition for drug loading treatment, the immersed length of the end of the artificial blood vessel is 0.2 - 2 cm.

8. The method for loading drugs into artificial blood vessels according to claim 1 or 2, characterized in that, The artificial blood vessel is made by winding and sewing bovine pericardium.

9. The method for loading a drug into an artificial blood vessel according to claim 8, wherein, The thickness of the bovine pericardium is 0.2 - 0.9 mm.

10. The method for loading drugs into artificial blood vessels according to claim 8, characterized in that, The bovine pericardium is a bovine pericardium that has been subjected to anti-calcification treatment.

11. The method for loading drugs into artificial blood vessels according to claim 1 or 2, characterized in that, The prepared artificial blood vessel is aseptically treated and then packaged. Before implanting the artificial blood vessel, it is taken out and trimmed to the required length and port shape, and then the artificial blood vessel is subjected to drug loading treatment in the drug-loaded composition.

12. The method for loading drugs into an artificial blood vessel according to claim 11, characterized in that, The drug-loaded artificial blood vessel is soaked in sterile physiological saline for 0.5 - 30 min.

13. An artificial blood vessel obtained by the artificial blood vessel drug loading method according to any one of claims 1 - 12.

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