JP7702835B2 - Puncture positioning band - Google Patents

Description

The present invention relates to a puncture positioning band that makes it possible to easily position the tip of a puncture needle, which can be used to puncture the surface of the body to administer medicines or collect samples, to the desired position.

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

As part of such efforts, cell structures formed using scaffolds and sheet-like cell cultures in which cells are formed into a sheet have been developed (Non-Patent Document 2).
Regarding the applications of sheet-type cell cultures in treatment, research is underway on the use of cultured epidermal sheets to treat skin injuries caused by burns etc., the use of corneal epithelial sheet-type cell cultures to treat corneal injuries, and the use of oral mucosa sheet-type cell cultures for endoscopic resection of esophageal cancer, and some of these have already reached the stage of clinical application.

Another example of repairing damaged tissues by transplanting cells is CD34-positive cell therapy for severe lower limb disease. In this treatment, CD34-positive cells are dissolved in saline and injected intramuscularly into several dozen sites on both legs that are in a severely ischemic state (Non-Patent Document 3).

Haraguchi et al., Stem Cells Transl Med. 2012 Feb;1(2):136-41 Sawa et al., Surg Today. 2012 Jan;42(2):181-4 Fujita et al., Circulation Journal Vol.78, February 2014: 490-501

The present inventors have found that although cells have been administered into tissues by intramuscular injection as described above, it has not been possible to accurately administer cells to a specific location near the outside of an artery in the lower limb (e.g., tissues surrounding blood vessels, vascular sheaths, etc.) in cases where blood circulation in the arteries of the lower limbs has deteriorated (such as peripheral arterial disease (PAD) caused by arteriosclerosis or foot lesions caused by diabetes).
The present invention aims to solve these problems and provide a medical device that uses a simple mechanism and simple operations to accurately administer cells to a desired location, for example, a desired location near the outside of a lower limb artery.

In the course of intensive research to solve the above problems, the inventors discovered for the first time that if a ready-made needle of standard length is used as the puncture needle for administration and the administration location is determined using a band to guide the puncture needle, it is possible to administer the drug to the desired location with a simple procedure. Based on this discovery, the inventors continued their research and eventually completed the present invention.

That is, the present invention relates to the following.
[1]
A device to be positioned on a body surface, the device including a fixing band for fixing the device to the body surface and a main body having multiple needle insertion portions for guiding a puncture needle, the needle insertion portions being provided on the main body 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 is at a preset position.

[2]
The device described in [1], wherein the main body has multiple needle insertion portions at multiple angles so that the tip of the needle at the fully inserted position where the puncture needle stops is at multiple predetermined depths from the body surface.

[3]
The device according to claim 1, wherein the predetermined position is a position a predetermined minute distance away from an outer surface of a blood vessel whose position is previously determined by a blood vessel position detection means.

[4]
The device according to any one of [1] to [3], wherein the main body portion is made up of multiple parts supported by the same fixing band.

[5]
A device as described in [3] or [4], wherein the needle insertion portion is a plurality of needle guide holes corresponding to a plurality of different pre-determined positions along a single blood vessel, or a plurality of different pre-determined positions along a plurality of blood vessels.

[6]
The device according to any one of [1] to [5], wherein the needle insertion portion has a structure in which a tubular body extends on the side of the main body opposite the body surface.

[7]
The device according to any one of claims 1 to 6, wherein the fixing band has a sock-like structure.

[8]
A device described in any one of [1] to [7], in which the main body itself serves the function of fixing to the body surface instead of a fixing band.

[9]
The device according to any one of claims 1 to 8, wherein the object to be injected with the puncture needle is a cell.

The puncture band of the present invention has a needle insertion portion that guides the puncture needle so that the puncture needle is inserted obliquely into the skin at a specific angle. By inserting a puncture needle of a standard length into this needle insertion portion and injecting at the position where it stops in contact with the needle insertion portion, it is possible to administer accurately to a predetermined administration point.

According to the present invention, a simple mechanism and simple operations allow for accurate administration of cells or other agents to a desired location, improving workability and the effectiveness of treatment for a disease or disorder.

FIG. 1 is a diagram showing the basic structure of the present invention. FIG. 2 is a diagram illustrating the basic principle of the present invention. FIG. 3 is a diagram showing an example of the configuration of the puncture band of the present invention. FIG. 4 is a diagram showing still another example of the puncture band of the present invention. FIG. 5 is a schematic diagram for explaining the needle insertion part arrangement and angle determination method of the present invention. FIG. 6 is a diagram showing an example in which the needle insertion part of the present invention has a tubular body.

In the present invention, the term "cell suspension" refers to cells suspended in any medium. The cells may be in the form of single cells, or may be connected to each other via an intervening substance. The cells may contain any gene or a viral vector containing any gene. The cells may also be a cell culture. In the present invention, the cell culture refers to a product obtained through a cell culture step, and includes, but is not limited to, spheroids, sheet-shaped cell cultures, and fragments of sheet-shaped cell cultures.
In the present invention, the medium for suspending cells includes, but is not limited to, water, physiological saline, culture medium, buffer solution, diluent, cell preservation solution, and swelling bodies such as gels.

In the present invention, the term "sheet-shaped cell culture" refers to a sheet-shaped product in which cells are connected to each other. The cells may be connected to each other directly (including through cellular elements such as adhesion molecules) and/or through an intervening substance. The intervening substance is not particularly limited as long as it is a substance that can at least physically (mechanically) connect the cells to each other, and examples thereof include extracellular matrix. The intervening substance is preferably derived from cells, particularly from cells that constitute the cell culture. The cells are at least physically (mechanically) connected, but may also be functionally connected, for example, chemically or electrically. The sheet-shaped cell culture may be composed of one cell layer (single layer) or two or more cell layers (laminated (multilayered) body, for example, two layers, three layers, four layers, five layers, six layers, etc.). The sheet-shaped cell culture may also have a three-dimensional structure with a thickness exceeding that of a single cell, without the cells showing a clear layer structure. For example, in the vertical cross section of a sheet-shaped cell culture, the cells may not be uniformly aligned in the horizontal direction, but may be arranged unevenly (e.g., in a mosaic pattern).

The sheet-shaped cell culture preferably does not include a scaffold (support). Scaffolds are sometimes used in the art to attach cells to their surface and/or inside and maintain the physical integrity of the sheet-shaped cell culture; for example, membranes made of polyvinylidene difluoride (PVDF) are known, but the sheet-shaped cell culture of the present invention can maintain its physical integrity even without such a scaffold. In addition, the sheet-shaped cell culture of the present invention preferably consists only of substances derived from the cells that constitute the sheet-shaped cell culture, and does not include any other substances.

In the present invention, "crushed pieces of a sheet-shaped cell culture" refers to a sheet-shaped cell culture that has been crushed and divided into multiple crushed pieces. The size of the crushed pieces is not limited to the above, but it is preferable that the majority of the crushed pieces are large enough not to enter the microvessels and to pass through the inside of an injection needle. For example, the average length of the diagonal of the flat surface of the sheet shape is 30 μm to 1000 μm, preferably 100 μm to 500 μm. In the present invention, crushing can be performed by any known method that can obtain crushed pieces of the sheet-shaped cell culture, for example, by suspending a medium containing the sheet-shaped cell culture using a syringe and needle or a pipette.

The cells contained in the cell suspension of the present invention are not particularly limited as long as they can be administered into tissues, and include, for example, adhesive cells (adherent cells). Adherent cells include, for example, adhesive cells (adherent cells). Adherent cells include, for example, adhesive somatic cells (e.g., cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatic cells, pancreatic cells, kidney cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, synovial cells, chondrocytes, etc.) and stem cells (e.g., myoblasts, tissue stem cells such as cardiac stem cells, embryonic stem cells, pluripotent stem cells such as iPS (induced pluripotent stem) cells, mesenchymal stem cells, etc.). Somatic cells may be differentiated from stem cells, particularly iPS cells (iPS cell-derived adhesive cells). Non-limiting examples of cells contained in the cell suspension include myoblasts (e.g., skeletal myoblasts, etc.), mesenchymal stem cells (e.g., derived from bone marrow, adipose tissue, peripheral blood, skin, hair roots, 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.), hepatic cells (e.g., hepatic parenchymal cells, etc.), pancreatic cells (e.g., pancreatic islet cells, etc.), kidney cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, etc. Non-limiting examples of iPS cell-derived adhesive cells include iPS cell-derived cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatic cells, pancreatic cells, kidney cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells, synovial cells, chondrocytes, etc.
In one embodiment, the cells contained in the cell suspension of the present invention are particularly preferably cells capable of promoting angiogenesis, for example cells capable of secreting factors that promote angiogenesis, for example cytokines such as VEGF.

In the present invention, the term "target site in tissue" refers to the site in the target tissue where the cell suspension is administered. Examples of the target site in tissue include a site where damage (wound) exists in a living body, or the vicinity thereof. Damage (wound) includes, but is not limited to, damage and stenosis of blood vessels, and in such cases, the target site in tissue is in tissue near the blood vessel, preferably between the blood vessel wall and the surrounding tissue. In one embodiment, the target site in tissue is the vascular sheath around the vascular tissue. The target site in tissue may be determined in advance by ultrasound examination or CT examination before administration. In the present invention, "administering the cell suspension to the target site in tissue" includes forming a space for administering the cell suspension to the target site in tissue and administering the cell suspension to the space.

In the present invention, the cell suspension is administered into the tissue of a subject, preferably into the tissue surrounding the blood vessels of the subject, more preferably into the tissue surrounding the blood vessels near the lesion site of a subject with a disease of the lower limb. In one embodiment, the cell suspension is administered into the tissue surrounding the blood vessels of a patient with peripheral arterial disease at a lesion site where blood flow is deteriorated, for example, in the femoral adductor group of the lower limb, in the tissue surrounding the blood vessels. In one embodiment, by administering the cell suspension into the tissue surrounding the blood vessels near the lesion site, the blood flow can be improved, for example, by 35%, 40%, or 45% compared to a healthy state, for example, 7 days after administration. In one embodiment, by administering the cell suspension into the tissue surrounding the blood vessels near the lesion site, the blood flow can be improved, for example, by about 1.5 times, about 2 times, or about 2.5 times compared to the control saline solution.

In one embodiment, the subject to whom the cell suspension is administered by the medical device of the present invention has a disease of the lower limbs. Diseases of the lower limbs include any disease that impairs the lower limbs. Examples of such diseases include, but are not limited to, peripheral arterial disease, varicose veins, deep vein thrombosis, and diabetic foot disease. Preferably, the disease of the lower limbs in the present invention is a disease in which blood vessels in the lower limbs are narrowed or blocked, causing a deterioration in blood flow in the lower limbs, such as peripheral arterial disease. In the present invention, peripheral arterial disease includes, but is not limited to, arteriosclerosis obliterans, Buerger's disease, collagen disease, and the like, and particularly severe arteriosclerosis obliterans is referred to as severe lower limb ischemia.

In the present invention, "treating" includes all types of medically acceptable prophylactic and/or therapeutic interventions aimed at curing, temporarily relieving, or preventing a disease, etc. For example, "treating" includes medically acceptable interventions for various purposes, including delaying or stopping the progression of a disease associated with tissue abnormality, regressing or eliminating a lesion, preventing the onset of the disease, or preventing recurrence of the disease, etc.
Without being bound by any particular theory, it is believed that the effect of the cell suspension administered by the medical device of the present invention on diseases of the lower limbs is due to cytokines such as VEGF that are continuously secreted from cells contained in the administered cell suspension of the present invention acting directly and/or indirectly on cells in the ischemic area to promote angiogenesis.

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 portion 8 that guides a puncture needle 6 opened in the main body 1, and the needle insertion portion 8 opens in a direction tilted from a direction perpendicular to the main body contact surface 9 that contacts the body surface 2, and guides the puncture needle 6 in the tilted direction.
The inclination 10 of the needle insertion portion 8, i.e., the angle 10 from the normal to the contact surface of the main body, is set at an angle such that when the puncture needle 6 having a specified length 11 is guided by the needle insertion portion 8 to puncture the body surface 2, the tip of the puncture needle 6 is exactly at the position of the administration point 4 when the puncture needle 6 hits the needle insertion portion 8 and stops.

FIG. 2 illustrates the basic principle of the present invention.
Needle insertion part 8 opening in main body 1 opens at a specific angle 10 from the surface normal direction of main body contact surface 9 that contacts the body surface. This angle 10 is set so that when a puncture needle 6 having a specified length is loaded into syringe 5 and guided by needle insertion part 8 to perform puncture by an operator, the tip of puncture needle 6 is positioned exactly at administration point 4 at the position where the needle hits needle insertion part 8 and stops entering.

As shown in FIG. 2, since the puncture needles 6 are of the same length, the administration point 4 moves closer to the body surface as the angle 10 increases.
The prescribed length of the puncture needle 6 is strictly controlled if a standard product of the same specification is used, so if the angle 10 is the same, the depth of the administration point 4 from the body surface will be exactly the same.
Therefore, as long as the same standard puncture needle 6 is used, the technician only needs to insert the puncture needle until the syringe 5 is stopped by the needle insertion portion 8, and there is no need for the technician to go to the trouble of adjusting at what position the needle should be stopped in order to adjust the administration position.
As long as the positioning of the main body 1 relative to the body surface is accurate, the tip of the puncture needle 6 can be brought to the three-dimensionally accurate administration point 4 within the body by using the two-dimensional position and inclination angle 10 of the needle insertion portion 8 opening into the main body 1, provided that the puncture needle 6 is of the correct specification.

FIG. 3 shows an example of the configuration of the puncture band of the present invention.
In order to position the main body part 1 relative to the body surface 2, a fixing band 7 that is wrapped around the body surface 2 is wrapped around the body surface 2 of, for example, the lower limb, and the main body part 1 is connected and fixed by the fixing band 7 and a support 12. Since the position of the main body part 1 relative to the lower limb is determined in this manner, the accuracy of the installation position of the fixing band 7 ultimately determines the three-dimensional position accuracy of the administration point 4.

Since the main body 1 and the fixing band 7 are separate, the fixing band 7 does not require thickness, unlike the main body 1. Also, since they are separate, the fixing band 7 can be left as it is, accurately fixed to the body, and only the main body 1 can be detached and attached using the support 12, making it possible to replace it with a main body 1 having a different needle puncture portion 8 arrangement and administer to a different group of administration points.

FIG. 4 shows another example of the device of the present invention.
The fixing band 7 has multiple support body 12 grounding points, and after wrapping one fixing band 7 around the body surface, multiple main body parts 1 can be attached, making it possible to puncture and inject into different areas.
4, the main body 1 shown at the top is a cross-sectional view showing the inclination of the needle stick portion 8, and the main body 1 in the middle shows the two-dimensional position of the needle stick portion 8 as seen on the surface. The main body 1 shown at the bottom is a side view, so the needle stick portion is not visible.

As described above, the main body 1 has a three-dimensional position relative to the body determined by the fixing band 7 and the support 12, so that the three-dimensional position of the administration point 4 within the body is determined by determining the two-dimensional arrangement and inclination 10 of the needle insertion portion 8.
Therefore, by determining in advance an administration point 4 near the outside of a blood vessel 3 inside the body, the two-dimensional position and the inclination direction and angle of the needle insertion part on the main body 1 are determined.

To determine the placement and angle of needle puncture 8 of the present invention, the desired administration point 4 is first determined.
For this purpose, the desired administration point 4 is determined, for example, in three-dimensional coordinate positions by acquiring a CT image for a specific patient.
Then, based on the spatial arrangement of the fixing band 7, the support 12, and the main body 1, the arrangement, angle 10, and tilt direction of the needle insertion part 8 required for the tip of the puncture needle to be positioned exactly at the administration point 4 are determined.

The positioning of the needlestick part 8 to reach the same administration point 4 is determined by the depth from the body surface 2, which is determined by the angle 10 as shown in Figure 2, but there is a degree of freedom as to the direction from which the tilted needlestick part 8 reaches the administration point 4, as shown in the plan view of the main body part 1 in Figure 5. Therefore, the orientation of the tilted needlestick part to reach the administration point 4 can be appropriately determined according to the needs of the positioning of the needlestick part 8 on the main body part 1.
Since the location of the administration point 4 differs from patient to patient, the main body 1 is usually also a custom-made product for each patient.

For example, when injecting a cell suspension near the outer side of a lower limb artery, administration points 4 are set close to multiple arteries along the artery.

To prevent interference with the syringe 5, the needle prick portions 8 may be arranged at alternating inclinations so as to sandwich the blood vessel, and multiple sets of needle prick portions 8 may be provided on one main body portion 1.
The multiple needle puncture portions 8 are arranged along the blood vessels of the lower limbs, and may be arranged alternately to sandwich the blood vessels, or multiple sets of needle puncture portions 8 may be provided on the main body portion 1.

The needle insertion portion 8 may simply open into the thicker main body portion 1, or, as shown in FIG. 6, a tubular body 13 may extend from the main body portion 1 to the outside (the side opposite the main body portion contact surface 9 that contacts the body surface 2).

The above description has been given of the main body 1 being supported by the support 12 on the fixing band 7, but the main body 1 itself may be wrapped around the surface of the body and fixed, i.e., it may also serve as the fixing band. Also, the support 12 may simply be a connecting mechanism such as a snap mechanism, screw fastening, or engagement hook for connecting the fixing band 7 and the main body 1.

In the example shown in the figure, the fixing band 7 is a simple band, but it may be shaped like a sock, for example, to more accurately position the main body 1 relative to the lower leg. Instead of a sock-like shape, the fixing band 7 may be shaped to match the outer shape of the knee joint, for example.

In the explanation so far, the main body 1 has been configured so that the administration point 4 specific to a particular patient is determined by prior measurement of the patient using a CT scan or the like, and one or more needle insertion parts 8 are installed to match the administration point 4. However, the main body 1 may be configured so that multiple needle insertion parts 8 are opened at multiple angles within a predetermined range, and a needle insertion part 8 that matches the measured three-dimensional position of the patient's administration point 4 is selected from the multiple pre-opened needle insertion parts 8, and the cell suspension or the like is administered using the matching needle insertion part 8.

By using the puncture band of the present invention, the technician administering a cell suspension or the like does not need to observe, select or adjust the puncture depth or puncture position; he or she can simply insert a specified puncture needle 6 into a randomly determined needle insertion site 8, let the needle penetrate until it stops, and then perform the injection operation with a syringe 5, thereby having the excellent effect of accurately injecting into a plurality of administration points 4.

1: Main body 2: Body surface 3: Blood vessel 4: Administration point 5: Syringe 6: Puncture needle 7: Fixing band 8: Needle insertion part 9: Main body contact surface 10: Needle insertion part inclination 11: Puncture needle specified length 12: Support 13: Tubular body

Claims (7)

A device to be positioned on a body surface, the device comprising a fixing band for fixing the device to the body surface, and a main body having multiple needle insertion portions for guiding a puncture needle, the needle insertion portions being provided on the main body 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 will be at a predetermined position, the predetermined position being a position a predetermined minute distance away from the outer surface of a blood vessel whose position is known in advance by a blood vessel position detection means, and the needle insertion portions being a plurality of needle guide holes corresponding to a plurality of different predetermined positions along a single blood vessel, or a plurality of different predetermined positions along a plurality of blood vessels . The device according to claim 1, in which the main body has multiple needle insertion parts at multiple angles so that the tip of the needle at the fully inserted position where the puncture needle stops is at multiple predetermined depths from the body surface. 3. The device of claim 1 or 2 , wherein the body portion is made up of multiple sections supported by the same fixing band. The device according to any one of claims 1 to 3 , wherein the needle insertion portion has a structure in which a tubular body extends on the side of the main body opposite the body surface. The device of any one of claims 1 to 4 , wherein the fixation band has a sock-like construction. The device according to any one of claims 1 to 5 , wherein the main body itself serves the function of fixing the device to the body surface instead of a fixing band. The device according to any one of claims 1 to 6 , wherein the object to be injected with the puncture needle is a cell.