Puncture position determination band

Abstract

To achieve a medical device for accurately administering a cell to a desired position, for example a desired position in the vicinity of the outside of the inferior limb, with a simple mechanism and simple work.SOLUTION: A puncture positioning band includes a puncture part that guides a puncture needle for allowing the puncture needle to diagonally enter the skin at a specific angle. By allowing the puncture needle having a standard length to enter the puncture part and performing injection at a position where the puncture needle contacts with the puncture part and stops, a cell can be accurately administered to a predetermined administration point.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a puncture positioning band that enables the tip position at the time of puncture of a puncture needle that can be used for administering drugs or the like or collecting specimens by puncturing the body surface to be easily brought to a desired position.

Background Art

[0002] In recent years, attempts have been made to transplant various cells for the repair of damaged tissues and the like. For example, for the repair of myocardial tissue damaged by ischemic heart diseases such as angina pectoris and myocardial infarction, the use of fetal cardiomyocytes, skeletal myoblasts, mesenchymal stem cells, cardiac stem cells, ES cells, iPS cells, etc. has been attempted (Non-Patent Document 1).

[0003] As part of such attempts, cell constructs formed using scaffolds and sheet-like cell cultures in which cells are formed into sheets have been developed (Non-Patent Document 2). Regarding the application of sheet-like cell cultures to treatment, studies have been conducted on the use of cultured epidermal sheets for skin damage caused by burns, the use of corneal epithelial sheet-like cell cultures for corneal damage, and the use of oral mucosal sheet-like cell cultures for endoscopic resection of esophageal cancer, and some of them have entered the stage of clinical application.

[0004] Also, as another example of the repair of damaged tissues and the like by transplantation of cells and the like, CD34-positive cell therapy for severe lower limb diseases can be mentioned. In such treatment, CD34-positive cells are dissolved in physiological saline and injected intramuscularly at dozens of locations on both feet in a severely ischemic state (Non-Patent Document 3).

Prior Art Documents

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0006] Although the present inventors have administered cells into tissues by intramuscular injection as described above, it has not been possible to accurately administer cells to a specific position such as near the outer side of the artery in the lower limb (e.g., perivascular tissue, vascular sheath, etc.) for a state where blood circulation in the lower limb artery has deteriorated (peripheral arterial disease (PAD) caused by arteriosclerosis, foot lesions due to diabetes, etc.). An object of the present invention is to solve such problems and realize a medical instrument for accurately administering cells to a desired position, for example, a desired position near the outer side of the lower limb artery, with a simple mechanism and simple operation.

Means for Solving the Problems

[0007] In order to solve the above problems, the present inventors, while conducting intensive research, found for the first time that if a needle having a standard length of an off-the-shelf product is used as a puncture needle for administration and a band for guiding the administration position with the puncture needle is used to define it, it becomes possible to administer to a desired position with a simple procedure. As a result of further research based on such findings, the present invention has been completed.

[0008] That is, the present invention relates to the following. [1] A device positioned on the body surface, the device including a fixing band for fixing to the body surface and a main body portion having a plurality of needle puncture portions for guiding a puncture needle, the needle puncture portions being provided on the main body portion at an angle such that when a puncture needle of a specified length is completely inserted until the needle stops, the tip of the needle reaches a preset position, said device. [2] The device according to [1], wherein the main body portion has a plurality of needle puncture portions at a plurality of angles such that the tip of the needle at the complete insertion position where the puncture needle stops has a plurality of depths predetermined from the body surface. [3] The device according to [1], wherein the preset position is a position separated by a preset minute distance from the outer surface of a blood vessel whose position has been previously determined by a blood vessel position detecting means. [4] The device according to any one of [1] to [3], wherein the main body portion consists of a plurality of parts supported by the same fixing band. [5] The device according to [3] or [4], wherein the needle puncture portions are a plurality of needle guide holes corresponding to a plurality of different preset positions along one blood vessel or a plurality of different preset positions along a plurality of blood vessels.

[0009] [6] The device according to any one of [1] to [5], wherein the needle puncture portions include those having a structure in which a tubular body extends to the side opposite to the body surface of the main body portion. [7] The device according to any one of [1] to [6], wherein the fixing band has a sock-like structure. [8] The device according to any one of [1] to [7], wherein instead of the fixing band, the main body portion itself functions to fix to the body surface. [9] The device according to any one of claims 1 to 8, wherein what is injected with the puncture needle is cells.

[0010] The puncture band of the present invention has a puncturing part for guiding a puncture needle to obliquely penetrate the skin at a specific angle with respect to the skin. By inserting a puncture needle of a standard length into this puncturing part and performing injection at the position where it abuts and stops against the puncturing part, it becomes possible to accurately administer to a predetermined administration point.

Advantages of the Invention

[0011] According to the present invention, with a simple mechanism and simple operation, it is possible to accurately administer a therapeutic agent such as cells to a desired position, so that workability and the therapeutic effect on a disease or disorder can be enhanced.

Brief Description of the Drawings

[0012]

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Embodiments for Carrying Out the Invention

[0013] In the present invention, the "cell suspension" refers to a suspension of cells in an arbitrary medium. The cells may be in a single cell state, or the cells may be connected to each other via an intervening substance. The cells may contain any gene or a viral vector containing any gene, etc. Further, the cells may be a cell culture. In the present invention, the cell culture refers to what is obtained through a cell culture step, and includes, but is not limited to, spheroids, sheet-like cell cultures, and fragments of sheet-like cell cultures. In the present invention, the medium for suspending the cells includes, but is not limited to, water, physiological saline, culture medium, buffer solution, diluent, cell preservation solution, and a swelling body such as a gel.

[0014] In the present invention, the "sheet-like cell culture" refers to a structure in which cells are connected to each other to form a sheet. The cells may be connected to each other directly (including those via cell elements such as adhesion molecules) and / or via an intervening substance. The intervening substance is not particularly limited as long as it can connect the cells to each other at least physically (mechanically), and examples thereof include the extracellular matrix. The intervening substance is preferably derived from cells, particularly from the cells constituting the cell culture. The cells are at least physically (mechanically) connected, but may be further functionally connected, for example, chemically or electrically. The sheet-like cell culture may be composed of one cell layer (single layer) or may be composed of two or more cell layers (laminated (multi-layer) body, for example, two layers, three layers, four layers, five layers, six layers, etc.). Further, the sheet-like cell culture may have a three-dimensional structure having a thickness exceeding the thickness of one cell without the cells showing a clear layer structure. For example, in a vertical cross-section of the sheet-like cell culture, the cells may exist in a state where they are arranged unevenly (for example, in a mosaic pattern) without being uniformly aligned in the horizontal direction.

[0015] The sheet-shaped cell culture preferably does not contain a scaffold (support). A scaffold may be used in the art to attach cells on its surface and / or inside thereof and maintain the physical integrity of the sheet-shaped cell culture. For example, a membrane made of polyvinylidene difluoride (PVDF) is known. However, the sheet-shaped cell culture of the present invention can maintain its physical integrity even without such a scaffold. Further, the sheet-shaped cell culture of the present invention preferably consists only of substances derived from the cells constituting the sheet-shaped cell culture and does not contain other substances.

[0016] In the present invention, the "fragment of the sheet-shaped cell culture" refers to a product obtained by crushing the sheet-shaped cell culture into a plurality of fragments. The size of the fragments is not limited thereto, but it is preferable that most of the fragments are sized such that they do not enter the microvessels and can pass through the inside of the injection needle. Such a size is, for example, such that the average of the diagonal lengths of the plane of the sheet shape is 30 μm to 1000 μm, preferably 100 μm to 500 μm. In the present invention, the crushing can be performed by any known method as long as fragments of the sheet-shaped cell culture can be obtained. For example, it can be performed by suspending a medium containing the sheet-shaped cell culture using a syringe and a needle or a pipette.

[0017] The cells contained in the cell suspension of the present invention are not particularly limited as long as they can be administered into a tissue, and include, for example, adherent cells (adhesive cells). The adherent cells include, for example, adherent cells (adhesive cells). The adherent cells include, for example, adherent somatic cells (e.g., cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatocytes, pancreatic cells, renal cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, synovial cells, chondrocytes, etc.) and stem cells (e.g., tissue stem cells such as myoblasts, cardiac stem cells, embryonic stem cells, pluripotent stem cells such as iPS (induced pluripotent stem) cells, mesenchymal stem cells, etc.). The somatic cells may be stem cells, particularly those differentiated from iPS cells (iPS cell-derived adherent cells). Non-limiting examples of the cells contained in the cell suspension include, for example, myoblasts (e.g., skeletal myoblasts, etc.), mesenchymal stem cells (e.g., those derived from bone marrow, adipose tissue, peripheral blood, skin, hair follicles, muscle tissue, endometrium, placenta, umbilical cord blood, etc.), cardiomyocytes, fibroblasts, cardiac stem cells, embryonic stem cells, iPS cells, synovial cells, chondrocytes, epithelial cells (e.g., oral mucosal epithelial cells, retinal pigment epithelial cells, nasal mucosal epithelial cells, etc.), endothelial cells (e.g., vascular endothelial cells, etc.), hepatocytes (e.g., liver parenchymal cells, etc.), pancreatic cells (e.g., islet cells, etc.), renal cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, etc. Non-limiting examples of iPS cell-derived adherent cells include iPS cell-derived cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatocytes, pancreatic cells, renal cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, synovial cells, chondrocytes, etc. In one aspect, the cells contained in the cell suspension of the present invention are particularly preferably cells that can promote angiogenesis, for example, cells that can secrete factors that promote angiogenesis, such as cytokines such as VEGF.

[0018] In the present invention, the "target site in the tissue" refers to the site in the target tissue where the cell suspension is administered. Examples of the target site in the tissue include, in a living body, a site where damage (wound) exists or its vicinity. The damage (wound) is not limited to these, but includes damage and stenosis of blood vessels. In such a case, the target site in the tissue is in the tissue near the blood vessel, preferably between the blood vessel wall and the surrounding tissue. In one aspect, the target site in the tissue is the vascular sheath around the vascular tissue. The target site in the tissue may be determined by ultrasonic examination, CT examination, etc. before administration. In the present invention, "administering a cell suspension to the target site in the tissue" includes forming a space for administering the cell suspension to the target site in the tissue and administering the cell suspension to the space.

[0019] In the present invention, the cell suspension is administered into the tissue of the subject, preferably into the tissue around the blood vessels of the subject, more preferably into the tissue around the blood vessels near the lesion site of the subject having a disease of the lower extremities. In one aspect, the cell suspension is administered into the tissue around the blood vessels at the lesion site where blood flow has deteriorated in a patient with peripheral arterial disease, for example, into the tissue around the blood vessels in the adductor muscle group of the thigh of the lower extremities. In one aspect, by administering the cell suspension into the tissue around the blood vessels near the lesion site, for example, 7 days after administration, the blood flow can be improved by, for example, 35%, 40%, 45% compared to the healthy state. In one aspect, by administering the cell suspension into the tissue around the blood vessels near the lesion site, the blood flow can be improved by, for example, about 1.5 times, about 2 times, about 2.5 times compared to the control physiological saline.

[0020] In one aspect, the subject to whom the cell suspension is administered by the medical device of the present invention has a disease of the lower limb. The diseases of the lower limb include any disease having a disorder in the lower limb. Examples of such diseases include, but are not limited to, peripheral arterial disease, aneurysm of the lower limb vein, deep vein thrombosis, and diabetic foot lesions. Preferably, the disease of the lower limb in the present invention is a disease in which the blood vessels in the lower limb are stenosed or occluded and the blood flow in the lower limb is deteriorated, for example, peripheral arterial disease. In the present invention, peripheral arterial disease includes, but is not limited to, atherosclerotic obliterans of the lower limb, Buerger's disease, collagen disease, etc., and particularly severe atherosclerotic obliterans of the lower limb is referred to as severe limb ischemia.

[0021] In the present invention, "treating" shall include performing all types of medically acceptable preventive and / or therapeutic interventions aimed at, for example, curing a disease, providing temporary remission, or preventing the disease. For example, "treating" includes performing various medically acceptable interventions, including delaying or stopping the progression of a disease associated with tissue abnormalities, regression or disappearance of lesions, preventing the onset of the disease, or preventing recurrence. Without being bound by a particular theory, the action of the cell suspension administered by the medical device of the present invention on the diseases of the lower limb is considered to be due to cytokines such as VEGF continuously secreted from the cells contained in the cell suspension of the present invention administered, acting directly and / or indirectly on the cells at the ischemic site, and promoting angiogenesis.

[0022] Fig. 1 shows the basic structure of the present invention. The device of the present invention has a main body 1 and a needle insertion part 8 for guiding a puncture needle 6 opened in the main body 1. The needle insertion part 8 is opened in a direction inclined from a direction perpendicular to the main body contact surface 9 where the main body 1 contacts the body surface 2, and guides the puncture needle 6 in the inclined direction. The inclination 10 of the puncturing portion 8, that is, the angle 10 from the normal line of the main body portion contact surface, is such that when the puncturing needle 6 having a specified length 11 is guided by the puncturing portion 8 and punctures the body surface 2, at the position where the puncturing needle 6 hits the puncturing portion 8 and stops, the tip is exactly at the position of the administration point 4.

[0023] Fig. 2 shows the basic principle of the present invention. The puncturing portion 8 opened in the main body portion 1 is inclined and opened by a specific angle 10 from the normal line direction of the main body portion contact surface 9 in contact with the body surface. This angle 10 is such that when a puncturing needle 6 having a specified length is loaded into the syringe 5 and guided by the puncturing portion 8 and the operator performs puncturing, at the position where the puncturing needle 6 hits the puncturing portion 8 and the penetration of the needle stops, the tip of the puncturing needle 6 is exactly at the position of the administration point 4.

[0024] As shown in Fig. 2, since the puncturing needles 6 of the same length are used, as the angle 10 increases, the administration point 4 moves toward the body surface side. If the specified length of the puncturing needle 6 uses the same standard product, it is strictly controlled. Therefore, if the angle 10 is the same, the depth of the administration point 4 from the body surface exactly coincides. Therefore, as long as the puncturing needles 6 of the same standard are used, the operator only needs to insert the puncturing needle until the syringe 5 is stopped by the puncturing portion 8, and there is no trouble for the operator to adjust at which position to stop for adjusting the administration position. As long as the positioning of the main body portion 1 with respect to the body surface is accurate, the two-dimensional position and the inclination angle 10 of the puncturing portion 8 opened in the main body portion 1 can surely bring the tip of the puncturing needle 6 to the three-dimensionally accurate administration point 4 in the body if the puncturing needle 6 is of the correct standard.

[0025] Fig. 3 shows an example of the configuration of the puncturing band of the present invention. In order to position the main body part 1 with respect to the body surface 2, a fixing band 7 that wraps around the body surface 2 is wound around the body surface 2 of, for example, the lower limb, and the main body part 1 is fixedly coupled by the fixing band 7 and the support 12. Since the position of the main body part 1 with respect to the lower limb is thereby defined, the installation position accuracy of the fixing band 7 ultimately defines the three-dimensional position accuracy of the administration point 4.

[0026] Since the main body part 1 and the fixing band 7 are separate bodies, unlike the main body part 1, the fixing band 7 is not required to have a thickness. Also, since they are separate bodies, the fixing band 7 that is accurately fixed to the body is left as it is, and only the main body part 1 is detached and attached by the support 12 and replaced with a main body part 1 having a different arrangement of the puncturing part 8, so that administration for another group of administration points can be carried out.

[0027] FIG. 4 shows another example of the device of the present invention. The fixing band 7 is provided with a plurality of grounding locations for the support 12. After the fixing band 7 is wound around the body surface, a plurality of main body parts 1 can be attached to perform puncturing and injection at different sites. This is an example. In FIG. 4, the main body part 1 shown at the top shows the inclination of the puncturing part 8 in a sectional view, and the middle main body part 1 shows the two-dimensional position of the puncturing part 8 visible on the surface. The main body part 1 shown at the bottom shows a side view, so the puncturing part cannot be seen.

[0028] As described above, since the relative three-dimensional position of the main body part 1 with respect to the body is defined by the fixing band 7 and the support 12, the three-dimensional position of the administration point 4 in the body is determined by determining the two-dimensional arrangement and the inclination 10 of the puncturing part 8. Therefore, if the administration point 4 near the outside of the blood vessel 3 in the body is predetermined, the two-dimensional position and the direction and angle of the inclination of the puncturing part in the main body part 1 are determined.

[0029] In order to determine the arrangement and the inclination of the puncturing part 8 of the present invention, first, a desired administration point 4 is determined. Therefore, for the desired administration point 4, for example, a CT image is obtained for a specific patient, and the three-dimensional position is determined coordinately. Then, based on the spatial arrangement of the fixing band 7, the support 12, and the main body 1, the arrangement, angle 10, and inclination direction of the puncturing part 8 necessary for the puncturing needle tip to be exactly positioned at the administration point 4 are determined.

[0030] The arrangement of the puncturing part 8 for reaching the same administration point 4 is such that the depth from the body surface 2 is defined by the angle 10 as shown in FIG. 2. However, regarding the direction from which the inclined puncturing part 8 reaches the administration point 4, there is freedom as shown in the plan view of the main body 1 in FIG. 5. Therefore, according to the necessity of the arrangement of the puncturing part 8 in the main body 1, the orientation of the inclined puncturing part for reaching the administration point 4 may be appropriately determined. Since the position of the administration point 4 varies from patient to patient, the main body 1 is usually a made-to-order product for each patient.

[0031] When injecting a cell suspension near the outer side of the lower limb artery, for example, a plurality of administration points 4 close to the arteries are set along the artery.

[0032] To prevent interference with the syringe 5, the puncturing parts 8 may be arranged to be alternately inclined so as to sandwich the blood vessel, or a plurality of sets of puncturing parts 8 may be provided on a single main body 1. The plurality of puncturing parts 8 are arranged along the blood vessels of the lower limb and may be alternately arranged so as to sandwich the blood vessel, or a plurality of sets of puncturing parts 8 may be provided on the main body 1.

[0033] The puncturing part 8 may simply be an opening in the main body 1 with a large thickness, or as shown in FIG. 6, a tubular body 13 may extend from the main body 1 to the outside (the opposite side of the main body contact surface 9 where the body surface 2 contacts).

[0034] Although the main body 1 has been described as being supported by the fixing band 7 by the support 12, the main body 1 itself may be configured to be wound around and fixed to the body surface, that is, to also serve as the fixing band. Further, the support 12 may simply be a coupling mechanism such as a snap mechanism, a screw fastening, or an engaging hook for coupling the fixing band 7 and the main body 1.

[0035] In the example of the figure, the fixing band 7 was a simple band, but it may be, for example, in the shape of a sock so that the positioning of the main body 1 with respect to the lower limb becomes more accurate. Instead of the sock-like one, for example, the fixing band 7 formed to conform to the outer shape of the knee joint may be used.

[0036] In the description so far, the main body 1 has been one in which the administration point 4 specific to a particular patient is determined by pre-measurement using the patient's CT or the like, and one or more puncture portions 8 are provided to conform to the administration point 4. However, using a main body 1 in which a large number of puncture portions 8 having a plurality of angles within a predetermined range are provided and opened, a puncture portion 8 that conforms to the three-dimensional position of the actually measured administration point 4 of the patient may be selected from the large number of pre-opened puncture portions 8, and administration of a cell suspension or the like may be performed using the conforming puncture portion 8.

[0037] By using the puncture band of the present invention, a technician who performs administration of a cell suspension or the like can insert the specified puncture needle 6 into the arbitrarily determined puncture portion 8 without observing, selecting, or adjusting the puncture depth or the puncture position, and when the needle has penetrated until it stops, simply perform an injection operation with the syringe 5, and there is an excellent effect that injection can be accurately performed at a plurality of administration points 4.

Explanation of Signs

[0038] 1: Main body 2: Body surface 3: Blood vessel 4: Administration point 5: Syringe 6: Puncture needle 7: Fixing band 8: Acupuncture part 9: Body part contact surface 10: Inclination of acupuncture part 11: Specified length of puncture needle 12: Support 13: Tubular body

Claims

Claim 1 A device positioned on the body surface, the device including a fixing band for fixing to the body surface and a main body portion having a plurality of needle puncture portions for guiding a puncture needle, the needle puncture portions being provided on the main body portion at an angle such that when a puncture needle of a specified length is fully inserted until the needle stops, the tip of the needle reaches a preset position, the preset position being a position separated by a preset minute distance from the outer surface of a blood vessel whose position has been previously determined by a blood vessel position detecting means, and the needle puncture portions being a plurality of needle guide holes corresponding to a plurality of different preset positions along one blood vessel or a plurality of different preset positions along a plurality of blood vessels, said device. Claim 2 The device according to claim 1, wherein the main body portion has a plurality of needle puncture portions at a plurality of angles such that the tip of the needle at the fully inserted position where the puncture needle stops has a plurality of depths preset from the body surface. Claim 3 The device according to claim 1 or 2, wherein the main body portion consists of a plurality of parts supported by the same fixing band. Claim 4 The device according to any one of claims 1 to 3, wherein the needle puncture portions include those having a structure in which a tubular body extends on the side opposite to the body surface of the main body portion. Claim 5 The device according to any one of claims 1 to 4, wherein the fixing band has a sock-like structure. Claim 6 The device according to any one of claims 1 to 5, wherein instead of the fixing band, the main body portion itself functions to fix to the body surface. Claim 7 The device according to any one of claims 1 to 6, wherein what is injected with the puncture needle is cells.

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