Pain treatment agent and agent for determining the administration site of particulate embolic material

Abstract

The present invention addresses the problem of providing a technique for treating a sports injury or a pain associated with a sports injury.　Provided is a therapeutic agent for a sports injury or a pain associated with a sports injury, the therapeutic agent containing a particulate embolic material having an average diameter of 10-500 μm inclusive, and the therapeutic agent being administered into an artery that nourishes the affected area of the sports injury and / or into an artery that nourishes the painful area associated with the sports injury.

Description

[Technical Field]

[0001] The present invention relates to a therapeutic agent for pain and an agent for determining the administration site of a particulate embolic material. [Background technology]

[0002] There are many causes of pain, but the present inventor has discovered that one of the causes is abnormal blood flow due to an increase in abnormal capillaries (known as "moyamoya vessels") (see, for example, Non-Patent Document 1). Such abnormal capillaries are generated in association with nerve proliferation, etc.

[0003] Based on the above findings, the present inventors have established a method for treating pain by delivering an embolic substance (such as imipenem / cilastatin particles) to abnormal capillaries, thereby clogging the abnormal capillaries. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Yuji Okuno, "The pain of Heberden's nodes is caused by hazy blood vessels," 2020, Wani Books Summary of the Invention [Problem to be solved by the invention]

[0005] Incidentally, the present inventors have discovered that abnormal capillaries are also formed in patients with so-called "sports injuries" caused by excessive exercise.

[0006] However, in sports injuries, it is difficult to accurately identify the abnormal capillaries that need to be blocked, and it has been found that there is a concern that administering an excessive amount of embolic material to an inappropriate area could actually worsen the symptoms.

[0007] The present invention has been made in view of the above circumstances, and aims to provide a technique for treating sports injuries or pain associated with sports injuries. [Means for solving the problem]

[0008] The present inventors have developed a therapeutic agent suitable for treating sports injuries and further discovered a method for determining an appropriate administration site for the therapeutic agent, thereby completing the present invention. More specifically, the present invention provides the following.

[0009] <1> A therapeutic agent for sports injuries or pain associated with sports injuries, The therapeutic agent contains a particulate embolic material having an average particle size of 10 μm or more and 500 μm or less, The therapeutic agent is administered into an artery supplying the affected area of ​​the sports injury and / or into an artery supplying the painful area associated with the sports injury. Therapeutic agent.

[0010] <2> A therapeutic agent for sports injuries or pain associated with sports injuries, The therapeutic agent contains a particulate embolic material having an average particle size of 10 μm or more and 500 μm or less, The therapeutic agent is administered to one or more of the following sites: (1) Sites where abnormal findings were found based on imaging of blood vessels at the candidate administration site located within the artery supplying the affected area of ​​the sports injury and / or the artery supplying the painful area associated with the sports injury. (2) administering a contrast agent having an osmotic pressure higher than that of blood to the candidate administration site; liquid or embolic material with a higher osmotic pressure than blood liquid After administration, discomfort occurred in the affected area

[0011] <3> 1. An agent for determining an administration site of a particulate embolic material for treating a sports injury or pain associated with a sports injury, comprising: The agent is a contrast agent having a higher osmolality than blood. liquid or embolic material with a higher osmotic pressure than blood liquid Including, the agent is administered to a candidate administration site and is used to determine the candidate administration site as an administration site for a particulate embolic material based on whether or not the agent causes discomfort in the affected area; The candidate administration site is located in an artery supplying the affected area of ​​a sports injury and / or in an artery supplying the painful area associated with a sports injury, The particulate embolic material has an average particle size of 10 μm or more and 500 μm or less. A particulate embolic substance administration site determination agent. [Effects of the Invention]

[0012] According to the present invention, a technique for treating sports injuries or pain associated with sports injuries is provided. DETAILED DESCRIPTION OF THE INVENTION

[0013] Hereinafter, an embodiment of the present invention will be described, but the present invention is not limited to this.

[0014] <Therapeutic agent> The therapeutic agent of the present invention is a therapeutic agent for sports injuries or pain associated with sports injuries. The therapeutic agent contains particulate embolic material with an average particle size of 10 μm or more and 500 μm or less, and is administered into the artery supplying the affected area of ​​the sports injury and / or the artery supplying the painful area associated with the sports injury.

[0015] As described above, the present inventor has developed a method for treating pain by injecting an embolic substance into abnormal capillaries to clog the abnormal capillaries and normalize blood flow. The present inventors then discovered that the cause of sports injuries is abnormal capillary proliferation, and made the novel discovery that the above-mentioned treatment method can treat sports injuries or pain associated with sports injuries.

[0016] (1) Sports injuries In the present invention, the term "sports injuries" includes injuries caused by various types of exercise (ball games, gymnastics, etc.) that place a heavy burden on the body. The presence and type of sports injury can be determined by a doctor's diagnosis.

[0017] In the present invention, the term "sports injury" includes both those accompanied by pain and those not accompanied by pain. When a sports injury is accompanied by pain, the pain is also a target for treatment according to the present invention.

[0018] The affected area of ​​a sports injury may include any part of the body. For example, sports injuries can affect the shoulder, elbow, lower back, back, hip, knee, ankle, foot, or wrist.

[0019] When the sports injury involves the shoulder, the sports injury includes throwing shoulder injuries, shoulder impingement syndrome, painful rotator cuff tears, SLAP injuries, rotator cuff spasm, long head biceps tendonitis, calcific tendonitis, and tendonitis.

[0020] When the sports injury involves the elbow, examples of the injury include medial collateral ligament injury, stress fracture of the olecranon, lateral epicondylitis of the humerus, medial epicondylitis of the humerus, synovial fold injury, elbow synovitis, osteochondritis dissecans, and other pain in the elbow joint caused by sports.

[0021] When the sports injury affects the lower back and / or back, the sports injury includes lumbar spondylolysis, facet joint lower back pain, lumbar facet arthritis, thoracic facet arthritis, myofascial lower back pain, interspinous ligament inflammation, lumbar disc herniation, intervertebral disc endplate inflammation, sacroiliac joint inflammation, and other sports-related lower back pain.

[0022] When the sports injury involves the hip joint, it can include hamstring enthesitis, hip synovitis, hip labral tears, hip impingement syndrome, groin pain syndrome, greater trochanter bursitis, and other sports-related hip pain.

[0023] When the sports injury involves the knee joint, it includes patellar tendonitis, patellofemoral tendonitis, iliotibial band syndrome, anserine bursitis, infrapatellar fat pad inflammation, medial collateral ligament injury, meniscus injury, Osgood-Schlatter disease, synovial fold disorder, separated patella, and other sports-related knee joint pain.

[0024] When the sports injury affects the ankle and / or foot, it includes Achilles tendonitis, plantar fasciitis, painful peroneal tendonitis, ankle impingement syndrome, hallux valgus, Morton's neuroma, posterior tibial tendonitis, ankle synovitis, MP arthritis, and other sports-related pain in the ankle and foot.

[0025] When the sports injury involves the wrist, it can include TFCC tears, tendonitis, scaphoid fractures, wrist synovitis, and other sports-related wrist pain.

[0026] Other sports injuries include recurrent muscle strain, stress fracture, delayed healing of fractures, and false joints.

[0027] (2) Embolic material The embolic substance used is a particulate substance with an average particle size of 10 μm or more and 500 μm or less.

[0028] In the present invention, the term "embolic substance" refers to a substance that can block blood flow in an artery.

[0029] The average particle size of the embolic substance can be adjusted appropriately depending on the diameter of the artery to be embolized, etc.

[0030] The lower limit of the average particle size of the embolic substance is preferably 30 μm or more, more preferably 50 μm or more, from the viewpoint of facilitating the embolization effect on the artery to be embolized.

[0031] The upper limit of the average particle size of the embolic material is preferably 350 μm or less, more preferably 250 μm or less, from the viewpoint of easily avoiding clogging of unintended arteries other than abnormal capillaries and facilitating delivery to the artery to be embolized.

[0032] In the present invention, the "average particle size" refers to the average value of particle size distribution, and is determined using a laser diffraction particle size distribution analyzer (for example, the "SALD" series, manufactured by Shimadzu Corporation).

[0033] The shape of the embolic material is not particularly limited, but may be irregular, spherical, angular, or the like.

[0034] The embolic substance is not particularly limited as long as it can block the blood flow in the artery and does not have any harmful effect on the living body.

[0035] Examples of materials for the embolic substance include materials that are poorly soluble in blood at body temperature (for example, 35 to 39°C), and specific examples include imipenem and cilastatin. However, in order to prevent the possibility of clogging a normal blood vessel if the embolic substance strays into the blood vessel, the embolic substance may be a material that is temporarily poorly soluble in blood at body temperature (e.g., 35 to 39°C) but eventually dissolves in blood at body temperature.

[0036] A preferred embodiment of the present invention includes an embodiment in which the embolic substance is a particulate embolic substance that contains a water-soluble polymer and satisfies both of the following (A) and (B): (A) 0.2 g of the substance is mixed with 30 cc of physiological saline at 37°C, and the "diffraction intensity / scattered light intensity" 10 minutes later is 10% or more of the "diffraction intensity / scattered light intensity" immediately after mixing. (B) 0.2 g of the substance is mixed with 30 cc of physiological saline at 37°C, and the "diffraction intensity / scattered light intensity" one hour later is 90% or less of the "diffraction intensity / scattered light intensity" immediately after mixing. (The "diffraction intensity / scattered light intensity" is measured for the mixed liquid using a laser diffraction particle size distribution analyzer "SALD-2300" (manufactured by Shimadzu Corporation) and a palindrome cell "BC23" (manufactured by the same company) at a refractive index of 1.65-0.20i.)

[0037] "Diffraction intensity / scattered light intensity" is the value obtained by dividing the diffraction intensity of particulate embolic material by the scattered light intensity of particulate embolic material. For particulate embolic materials that satisfy both (A) and (B), the "diffraction intensity / scattered light intensity" at three time points during the preparation of the saline solution (i.e., immediately after preparation, 10 minutes after preparation, and 1 hour after preparation) was used as an index of the appropriate size of the embolic material according to the course of administration.

[0038] When comparing the "diffraction intensity / scattered light intensity" at each time point, first identify the sensor from the "SALD-2300" (which has 65 sensors) that showed the highest "diffraction intensity / scattered light intensity" measured immediately after mixing. Next, the "diffraction intensity / scattered light intensity" of the sensor immediately after mixing is compared with the "diffraction intensity / scattered light intensity" at a later time point (10 minutes or 1 hour later).

[0039] If (A) is less than 10%, the particulate embolic material dissolves too quickly in the body, making it difficult to embolize abnormal blood vessels and resulting in a poor pain treatment effect. Therefore, (A) is preferably 30% or more, more preferably 50%. The upper limit of (A) is not particularly limited, but from the viewpoint of easily achieving an appropriate embolic material size, it is preferably 100% or less, more preferably 98% or less, and even more preferably 95% or less. However, (A) has a higher value than (B) described below.

[0040] If (B) exceeds 90%, the particulate embolic material will not dissolve quickly in the body and will be more likely to clog normal blood vessels that nourish joints, resulting in severe side effects such as pain after administration. Therefore, (B) is preferably 70% or less, more preferably 30% or less. The lower limit of (B) is not particularly limited, but from the viewpoint of easily achieving an appropriate embolic material size, it is preferably 1% or more, more preferably 3% or more, and even more preferably 5% or more.

[0041] The ratio of (A) to (B) is not particularly limited as long as it satisfies (A)>(B). The lower limit of "(A) / (B)" (the value obtained by dividing (A) by (B)) can be, for example, 1.01 or more, 1.50 or more, 2.00 or more, or 3.00 or more. The upper limit of "(A) / (B)" can be, for example, 10.00 or less, 9.00 or less, 8.00 or less, 7.00 or less, 6.00 or less, or 5.00 or less.

[0042] The water-soluble polymer is not particularly limited as long as it has gelling ability, and examples thereof include non-crosslinked polymers such as agar, gelatin, collagen, and curdlan, and crosslinked polymers such as sodium alginate, sodium polyacrylate, pectin, and carrageenan. The embolic substance may or may not contain a polymer other than the water-soluble polymer. A short-dissolving hydrogel, which is formed by dispersing such a water-soluble polymer in water to form a three-dimensional structure, can be used as the embolic substance in one embodiment. By appropriately adjusting the hydrophilicity, molecular weight, and crosslinking density of the water-soluble polymer, an embolic substance satisfying conditions (A) and (B) can be produced, although this is not particularly limited. Commercially available embolic substances include "IPZA100-300" and "IPZA300-500" manufactured by Engain, Inc., and "Nexsphere" manufactured by Nextbiomedical, Inc.

[0043] The therapeutic agent of the present invention is an agent administered by injection into an artery. Therefore, the therapeutic agent of the present invention may contain, as needed, a vehicle that can be administered into a living artery (such as a physiological buffer solution, sterile water, physiological saline, a culture medium, or a contrast agent) or any component that can be contained in an injection, together with the embolic substance, within a range that does not impair the embolization effect of the embolic substance.

[0044] The therapeutic agent of the present invention may be in the form of an injection. The configuration of the injection is not particularly limited, and any configuration that allows administration to a recipient using an injection needle can be adopted. Typically, an injection preparation is provided with an injection needle (such as a Surflo indwelling needle) and a syringe, and the syringe is filled with an embolic substance or the like.

[0045] When administering the therapeutic agent of the present invention, angiography may be performed to identify the administration site of the therapeutic agent. For such imaging, a contrast agent may be used in combination with the embolic substance of the present invention. The type of contrast agent is not particularly limited, but examples include iohexol. The contrast agent may be incorporated into the therapeutic agent of the present invention (i.e., may be administered simultaneously with the embolic substance), or may be administered separately from the therapeutic agent of the present invention. When the contrast agent and the therapeutic agent of the present invention are administered separately, the order of administration is not particularly limited, but administering the contrast agent first is preferred from the viewpoint of making it easier to identify the administration site.

[0046] (3) Administration site The therapeutic agent of the present invention is administered into an artery supplying nutrients to the affected area of ​​a sports injury and / or into an artery supplying nutrients to the painful area associated with a sports injury.

[0047] The individual arteries listed below include not only the artery itself but also the branches that branch off from that artery.

[0048] From the viewpoint of facilitating efficient administration of the embolic substance to abnormal capillaries (moyamoya blood vessels), the administration site may be an artery that nourishes the painful area. Specifically, the "artery that nourishes the painful area" may be an artery located within 10 cm upstream of the painful area.

[0049] For intra-arterial administration, the therapeutic agents of the present invention may be administered using a catheter.

[0050] The diameter, shape, etc. of the catheter are not particularly limited as long as it is a tube with a luminal structure that can be inserted into an artery and into which an embolic substance can be injected. Usually, a catheter with an outer diameter of 0.6 to 1 mm (so-called microcatheter) can be suitably used.

[0051] When operating the catheter, devices and techniques commonly used in transcatheter administration, such as guide wires and pumps, can be used.

[0052] When administering via a catheter, either pressure injection or free flow can be selected as appropriate depending on the administration site, etc. For example, in areas where arteries communicate with each other, administration by pressure injection is preferred. In this case, it is desirable to ensure that a distance (e.g., 2 cm or more) is maintained from the spinal artery. For example, free flow is preferred from the viewpoint of reducing the risk of embolic material flowing into the spinal artery due to backflow caused by pressure injection.

[0053] In the present invention, a method for avoiding backflow during administration from a catheter includes administering an embolic substance at a location where it has been confirmed that the test-injected contrast agent naturally flows into the peripheral blood vessels (also known as washout).

[0054] In the injection administration, the configuration of the injection is not particularly limited, but any configuration that can be administered to a recipient using an injection needle suitable for intra-arterial injection therapy (direct puncture of an artery with a needle without using a catheter, etc.) can be adopted. Typically, an injection comprises an injection needle (such as a Surflow indwelling needle) and a syringe, and the syringe is filled with an embolic substance, etc.

[0055] When the sports injury involves the shoulder, the arteries that nourish the area affected by the sports injury and / or the area of ​​pain associated with the sports injury include the subscapular artery, thoracoacromial artery, coracoid branch, circumflex scapular artery, anterior circumflex humeral artery, and posterior circumflex humeral artery.

[0056] When the sports injury is in the elbow, the arteries that supply the area affected by the sports injury and / or the painful area associated with the sports injury include the deep brachial artery, radial collateral artery, ulnar collateral artery, radial recurrent artery, recurrent interosseous artery, and ulnar recurrent artery.

[0057] When the sports injury affects the lower back and / or back, the arteries that nourish the affected area and / or the painful area associated with the sports injury include the left and right first to fourth lumbar arteries, the iliolumbar arteries, the median sacral artery, the lateral sacral artery, the superior gluteal artery, the inferior gluteal artery, and the intercostal arteries.

[0058] When the affected area of ​​a sports injury is the hip joint, the arteries that supply the affected area and / or the painful area associated with the sports injury include the superior gluteal artery, inferior gluteal artery, obturator artery, deep iliac circumflex artery, inferior epigastric artery, medial femoral circumflex artery, and lateral femoral circumflex artery.

[0059] When the affected area of ​​a sports injury is the knee joint, the arteries that supply the affected area and / or the painful area associated with the sports injury include the descending genicular artery, superior medial genicular artery, superior lateral genicular artery, median genicular artery, inferior lateral genicular artery, inferior medial genicular artery, anterior tibial recurrent artery, and suprapatellar artery.

[0060] When the sports injury involves the ankle and / or foot, the arteries supplying the affected area and / or the painful area associated with the sports injury include the anterior tibial artery, posterior tibial artery, and peroneal artery.

[0061] When the affected area of ​​a sports injury is the wrist, the arteries supplying the affected area and / or the painful area associated with the sports injury include the radial artery, ulnar artery, and interosseous artery.

[0062] If the sports injury is a recurrent muscle strain, stress fracture, delayed healing of a fracture, or false joint, the artery that nourishes the affected area of ​​the sports injury and / or the artery that nourishes the painful area associated with the sports injury will differ depending on the location, so an artery that is thought to nourish the affected area (candidate administration site) will be selected, a catheter will be delivered, and selective angiography will be performed to identify the administration site.

[0063] (4) Identifying the administration site In sports injuries or pain associated with sports injuries, it can be difficult to identify the blood vessels responsible. If the therapeutic agent of the present invention is administered to a site other than the responsible blood vessel, it may clog blood vessels that are not appropriate for treatment or an excessive amount of the therapeutic agent may be administered, which may worsen the disorder or pain.

[0064] As a result of investigations conducted by the present inventors, it was found that the above-mentioned possibility can be avoided by administering the therapeutic agent to one or more of the following sites: (Site 1) Sites where abnormal findings were found based on imaging of blood vessels at candidate administration sites located within the arteries supplying nutrients to the affected area of ​​a sports injury and / or the painful area associated with a sports injury. (Site 2) A contrast agent having an osmotic pressure higher than that of blood is administered to the candidate administration site in (Site 1) above. liquid or embolic material with a higher osmotic pressure than blood liquid After administration, discomfort occurred in the affected area

[0065] In identifying any of the above sites, first, a "candidate administration site" is selected that is located within the artery that nourishes the affected area of ​​the sports injury and / or the painful area associated with the sports injury. Whether or not this candidate administration site is actually the blood vessel responsible for the sports injury or pain associated with the sports injury is determined by the following method. If the result of the determination is that the site does not fall under either (site 1) or (site 2), the therapeutic agent is not administered, and another candidate administration site is selected, and the responsible blood vessel is searched for based on whether it falls under (site 1) or (site 2).

[0066] (4-1) About part 1 The candidate administration site is imaged for blood vessels by any means. For example, the following steps can be used for imaging. First, a catheter is delivered to a candidate administration site, and an optional contrast agent is released into the candidate administration site. The candidate administration site is then radiographed and an x-ray image is obtained. Based on the obtained images, the presence or absence of abnormal findings at the candidate administration site is confirmed. Abnormal findings include, for example, the following: Deep staining: As a result of an increase in abnormal blood vessels, the contrast agent is distributed more in the affected area than in normal areas, making it appear as if only that area is stained. Early venous filling: A phenomenon in which veins become visible earlier (for example, while the artery is being visualized) than the usual timing when veins become visible after slowly passing through the artery and capillaries due to an abnormal connection between the artery and vein. If abnormal findings are observed based on the image, the candidate administration site can be determined to be the responsible blood vessel. Therefore, this site is identified as the administration site (the above (site 1)), and while the catheter is still positioned at the candidate administration site, the therapeutic agent of the present invention or the agent for determining the administration site of a particulate embolic material, described below, is administered. If it is clear from the images that there are no abnormal findings, the catheter is removed from the candidate administration site and delivered to another candidate administration site, and the above procedure is repeated.

[0067] (4-2) About part 2 Even if the presence or absence of abnormal findings at a candidate administration site is unclear based on imaging, the candidate administration site may still be a valid administration site. In such cases, a contrast agent having a higher osmolality than blood is administered to the candidate administration site. liquid or embolic material with a higher osmotic pressure than blood liquid Administer the drug and check whether it causes any discomfort in the affected area.

[0068] Contrast agents with higher osmolality than blood liquid or embolic material with a higher osmotic pressure than blood liquid The discomfort caused by administration of this drug includes pain (reproduced pain) that coincides with the location of pain associated with sports injuries, a feeling of heat that coincides with the location of pain associated with sports injuries, and itching that coincides with the location of pain associated with sports injuries. Furthermore, the timing at which the discomfort occurs may be, for example, any time from immediately after administration to within 10 minutes after administration at the candidate administration site, preferably any time from immediately after administration to 10 to 120 seconds after administration at the candidate administration site. If there is any discomfort, the candidate administration site can be determined to be the responsible blood vessel, and the therapeutic agent of the present invention is administered at this site (site 2 above).

[0069] The present inventors have developed a contrast agent with a higher osmotic pressure than blood. liquid and embolic substances with a higher osmotic pressure than blood liquid It has been found that this drug acts on the blood vessels responsible for sports injuries or pain associated with sports injuries, causing discomfort in the affected area, particularly pain similar to that associated with sports injuries (repeated pain).The presence or absence of such repetitive pain can be used as an indicator to identify the blood vessels responsible for sports injuries or pain associated with sports injuries.

[0070] In the present invention, a contrast agent having an osmotic pressure higher than that of blood is used to identify (site 2). liquid and embolic substances with a higher osmotic pressure than blood liquid corresponds to "an agent for determining the administration site of a particulate embolic material for the treatment of sports injuries or pain associated with sports injuries."

[0071] In addition, in the present invention, when it is unclear whether or not there are any abnormal findings at a candidate administration site, it is preferable to select whether or not to administer a particulate embolic substance administration site determination agent based on whether the candidate administration site is a blood vessel that normally nourishes the area of ​​pain. If the candidate administration site does not coincide with the usual site of pain, there is a possibility of excessive embolization of the normal site, resulting in pain and nerve damage, so it is preferable not to use the agent for determining the administration site of the particulate embolic agent. In this case, the catheter is removed from the candidate administration site and delivered to another candidate administration site, and abnormal findings are confirmed again.

[0072] (Contrast agents with higher osmolality than blood liquid ) In the present invention, a "contrast agent having an osmotic pressure higher than that of blood" liquid " is a contrast agent with an osmotic pressure higher than that of blood in the body (approximately 280 mOsm / kg). liquid means. For example, contrast agents with higher osmolality than blood liquid can be 1.2 times or more and 3.0 times or less the osmotic pressure of blood in a living body.

[0073] Contrast agents with higher osmolality than blood liquid Examples include Omnipark and Hexabrix. A liquid containing Examples include:

[0074] Contrast agents with higher osmolality than blood liquid teeth, Contrast agent It can be used in combination with a liquid (physiological saline) that can be administered to the living body. Contrast agents with higher osmolality than blood liquid The amount used is not particularly limited as long as it is an amount that can temporarily embolize the candidate administration site or cause recurrent pain, and can be set depending on the diameter of the blood vessel at the candidate administration site, etc.

[0075] For example, contrast agents with higher osmolality than blood liquid The amount used (amount administered to the proposed administration site) may be 0.2 to 3 ml (volume). liquid It may be administered at once or in several divided doses.

[0076] (An embolic substance with a higher osmotic pressure than blood) liquid ) In the present invention, "an embolic substance having an osmotic pressure higher than that of blood" liquid " refers to an embolic substance with an osmotic pressure higher than that of blood in the body (approximately 280 mOsm / kg). liquid means. Such embolic material liquid includes substances that, when administered into the artery of a healthy person (i.e., a person without sports injuries or pain associated with sports injuries), cause discomfort (pain, heat, itching, pressure, etc.) at the injection site within 10 minutes of administration.

[0077] Embolic material with a higher osmotic pressure than blood liquid Examples include Tienam (cilastatin sodium) A liquid containing Examples include:

[0078] Embolic material with a higher osmotic pressure than blood Embolic material contained in the fluid The average particle size and shape of the embolic substance are not particularly limited, and may be the same as those of the embolic substance contained in the therapeutic agent of the present invention described above. Embolic material with a higher osmotic pressure than blood Embolic material contained in the fluid The lower limit of the average particle size may be, for example, 10 μm or more, 20 μm or more, or 30 μm or more. Embolic material with a higher osmotic pressure than blood Embolic material contained in the fluid The upper limit of the average particle size may be, for example, 500 μm or less, 200 μm or less, or 100 μm or less.

[0079] Embolic material with a higher osmotic pressure than blood liquid teeth, Embolic material It can be used in combination with a liquid (physiological saline) that can be administered to the living body. Embolic material with a higher osmotic pressure than blood liquid The amount of the embolic substance used is not particularly limited as long as it is an amount that can temporarily embolize the candidate administration site. Embolic material contained in the fluid This can be set depending on the particle size of the drug, the diameter of the blood vessel at the proposed administration site, etc.

[0080] For example, embolic materials with a higher osmotic pressure than blood Embolic material contained in the fluid The amount used (amount administered to the proposed administration site) may be 10 to 500 mg (dry weight). The substance may be administered all at once or in several divided doses.

[0081] (5) Dosage of therapeutic agents, etc. The administration rate and frequency of the therapeutic agent of the present invention can be determined depending on the condition of the patient (age, body weight, severity of symptoms, etc.).

[0082] The administration of the therapeutic agent of the present invention can be terminated by any operation that can stop the injection of the therapeutic agent into the administration site, such as removing the syringe barrel from the administration site and applying pressure to stop bleeding.

[0083] <Therapeutic Effects of the Therapeutic Agent of the Present Invention> The therapeutic effect of the therapeutic agent of the present invention can be evaluated by any method for evaluating pain, such as a method based on the "Numerical Rating Scale (NRS) score" or a method in which patients subjectively answer the degree of improvement in pain ("Patients Global Impression of Change"). [Example]

[0084] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples.

[0085] In all of the following tests, in most patients in "(2-2) Cases where the presence or absence of abnormal findings was unknown," discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 to 120 seconds after administration (at the latest, within 10 minutes after administration).

[0086] <Preparing the treatment> In this example, one of the following embolic substances was used: Each embolic substance was prepared as an aqueous solution of 1 g / 10 ml.

[0087] (1) Imipenem-cilastatin The imipenem-cilastatin used was Primaxin (Merck & Co.). The average particle size of this embolic material was measured using a laser diffraction particle size distribution analyzer (SALD series, Shimadzu Corporation) and was found to be less than 70 μm.

[0088] (2) Gelatin preparations Commercially available gelatin preparations, "IPZA100-300" and "IPZA300-500" manufactured by Engain, and "Nexsphere" manufactured by Nextbiomedical, were used. All of these satisfy both (A) and (B) below. (A) 0.2 g of a substance is mixed with 30 cc of 37°C saline, and the "diffraction intensity / scattered light intensity" 10 minutes later is 10% or more of the "diffraction intensity / scattered light intensity" immediately after mixing. (B) 0.2 g of a substance is mixed with 30 cc of 37°C saline, and the "diffraction intensity / scattered light intensity" one hour later is 90% or less of the "diffraction intensity / scattered light intensity" immediately after mixing. (The "diffraction intensity / scattered light intensity" is measured for the mixed liquid using a laser diffraction particle size distribution analyzer "SALD-2300" (manufactured by Shimadzu Corporation) and a palindrome cell "BC23" (manufactured by the same company) at a refractive index of 1.65-0.20i.)

[0089] In this example, Iopaque (manufactured by Fuji Pharmaceutical Co., Ltd.) was used as the contrast agent. The contrast agent was mixed with the embolic material. The mixing ratio (mass ratio of the active ingredients) was set at 20 ml of contrast agent per 1 g of embolic material. The resulting solution was used in the following tests as a therapeutic agent.

[0090] <Preparation of the agent for determining the administration site of particulate embolic material> In this example, the following components were prepared as an agent for determining the administration site of a particulate embolic material.

[0091] (1) Contrast agents with higher osmotic pressure than blood liquid "Iopaque" was used as the contrast agent. A liquid containing has an osmotic pressure about twice as high as that of blood.

[0092] (2) Embolic material with a higher osmotic pressure than blood liquid Embolic material with a higher osmotic pressure than blood liquid "Tienam" (average particle size: 40 μm) A liquid containing was used. This embolic material has a higher osmotic pressure than blood liquid was prepared as a 1 g / 10 ml aqueous solution.

[0093] <Test 1: Treatment of sports shoulder injuries> In patients suffering from sports injuries of the shoulder or pain associated with such sports injuries, the administration site of the therapeutic agent was identified by the following method, and treatment with the therapeutic agent of the present invention was carried out.

[0094] (1)Patient The subjects were 10 people who regularly participated in sports and had abnormal findings in the shoulder. These patients had one of the following conditions: throwing shoulder injury, shoulder impingement syndrome, painful rotator cuff tear, SLAP injury, rotator cuff spasm, long head biceps tendonitis, calcific tendonitis, or tendonitis.

[0095] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (radial artery, inguinal artery, etc.), advanced to the axillary artery and subclavian artery, and angiography was performed. The target arteries (candidate administration sites) for shoulder sports injuries are usually the subscapular artery, thoracoacromial artery, coracoid branch, circumflex scapular artery, anterior circumflex humerus artery, or posterior circumflex humerus artery. All of these correspond to "arteries supplying the affected area of ​​shoulder sports injuries and / or arteries supplying the painful area associated with shoulder sports injuries." Therefore, catheters were delivered to these arteries and selective angiography was performed.

[0096] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 ml) was administered to the administration site.

[0097] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 ml) was administered.

[0098] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0099] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and the administration site was identified, and the therapeutic agent (approximately 0.2 ml) was administered.

[0100] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 ml) was administered.

[0101] (3) Results Two months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0102] <Study 2: Treatment of Elbow Sports Injuries> In the following manner, the administration site of the therapeutic agent was identified in patients suffering from sports injuries of the elbow or pain associated with the sports injuries, and treatment with the therapeutic agent of the present invention was carried out.

[0103] (1)Patient The subjects were 45 people who regularly participated in sports and had abnormal findings in the elbow. These patients had one of the following conditions: medial collateral ligament injury, olecranon stress fracture, lateral epicondylitis of the humerus, medial epicondylitis of the humerus, synovial fold disorder, elbow synovitis, osteochondritis dissecans, or other sports-related elbow pain.

[0104] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (radial artery, inguinal artery, etc.), advanced to the brachial artery, and angiography was performed. The target arteries (candidate administration sites) for elbow sports injuries are usually the deep brachial artery, radial collateral artery, ulnar collateral artery, radial recurrent artery, recurrent interosseous artery, or ulnar recurrent artery, all of which correspond to "arteries supplying the affected area of ​​elbow sports injuries and / or arteries supplying the painful area associated with elbow sports injuries." Therefore, catheters were delivered to these arteries and selective angiography was performed.

[0105] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 ml) was administered to the administration site.

[0106] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 ml) was administered.

[0107] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0108] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and the administration site was identified, and the therapeutic agent (approximately 0.2 ml) was administered.

[0109] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 ml) was administered.

[0110] (3) Results Three months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0111] <Study 3: Treatment of lower back and / or back sports injuries> In patients suffering from sports injuries of the lower back and / or back, or pain associated with such sports injuries, the administration site of the therapeutic agent was identified by the following method, and treatment with the therapeutic agent of the present invention was carried out.

[0112] (1)Patient The subjects were 15 people who regularly participated in sports and had abnormal findings in the lower back and / or back. These patients had one of the following diseases: lumbar spondylolysis, facet joint low back pain, lumbar facet arthritis, thoracic facet arthritis, myofascial low back pain, interspinous ligamentitis, lumbar disc herniation, disc endplate inflammation, sacroiliac joint inflammation, and other sports-related low back pain.

[0113] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (such as the inguinal artery), advanced to the abdominal aorta, and angiography was performed. The target arteries (candidate administration sites) for sports injuries of the lower back and / or back are usually the left and right first to fourth lumbar arteries, the iliolumbar arteries, the median sacral artery, the lateral sacral artery, the superior gluteal artery, the inferior gluteal artery, or the intercostal arteries. All of these correspond to "arteries supplying nutrients to the affected area of ​​a sports injury of the lower back and / or back, and / or arteries supplying nutrients to the painful area associated with a sports injury of the lower back and / or back." Therefore, catheters were delivered to these arteries and selective angiography was performed.

[0114] In the following, when administering a particulate embolic substance administration site determination agent or a therapeutic agent to the lumbar artery or intercostal artery, administration was performed after confirming that the artery to the spinal cord (Adamkiewicz artery) was not visualized. If an artery to the spinal cord was identified, administration was not performed, or the microcatheter was advanced sufficiently to avoid the artery and then advanced to a position where administration was possible before administration was performed.

[0115] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 to 0.5 ml) was administered to the administration site.

[0116] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 to 0.5 ml) was administered.

[0117] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 to 0.5 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0118] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and after identifying the administration site, the therapeutic agent (approximately 0.2 to 0.5 ml) was administered.

[0119] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 to 0.5 ml) was administered.

[0120] (3) Results Three months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0121] <Test 4: Treatment of hip sports injuries> In patients suffering from sports injuries of the hip joint or pain associated with such sports injuries, the administration site of the therapeutic agent was identified by the following method, and treatment with the therapeutic agent of the present invention was carried out.

[0122] (1)Patient The subjects were 17 people who regularly participated in sports and had abnormal findings in the hip joint. These patients had one of the following conditions: hamstring enthesitis, hip synovitis, hip labral tear, hip impingement syndrome, groin pain syndrome, greater trochanteric bursitis, or other sports-related hip pain.

[0123] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (such as the inguinal artery), advanced to the internal iliac artery, and angiography was performed. The target arteries (candidate administration sites) for hip sports injuries are usually the superior gluteal artery, inferior gluteal artery, obturator artery, deep iliac circumflex artery, inferior epigastric artery, medial femoral circumflex artery, or lateral femoral circumflex artery. All of these correspond to "arteries supplying the affected area of ​​a hip sports injury and / or arteries supplying the painful area associated with a hip sports injury." Therefore, catheters were delivered to these arteries and selective angiography was performed.

[0124] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 ml) was administered to the administration site.

[0125] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 ml) was administered.

[0126] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0127] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and the administration site was identified, and the therapeutic agent (approximately 0.2 ml) was administered.

[0128] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 ml) was administered.

[0129] (3) Results Three months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0130] <Test 5: Treatment of sports injuries of the knee joint> In patients suffering from sports injuries of the knee joint or pain associated with such sports injuries, the administration site of the therapeutic agent was identified by the following method, and treatment with the therapeutic agent of the present invention was carried out.

[0131] (1)Patient The subjects were 49 people who regularly participated in sports and had abnormal findings in their knee joints. These patients had one of the following conditions: patellar tendonitis, patellofemoral tendonitis, iliotibial band syndrome, anserine bursitis, infrapatellar fat pad inflammation, medial collateral ligament injury, meniscus injury, Osgood-Schlatter disease, synovial fold disorder, separated patella, or other sports-related knee pain.

[0132] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (such as the inguinal artery), advanced to the popliteal artery, and angiography was performed. The target arteries (candidate administration sites) for sports injuries of the knee joint are usually the descending genicular artery, superior medial genicular artery, superior lateral genicular artery, median genicular artery, inferior lateral genicular artery, inferior medial genicular artery, anterior tibial recurrent artery, or suprapatellar artery, all of which correspond to "arteries supplying nutrients to the affected area of ​​a sports injury of the knee joint and / or arteries supplying nutrients to the painful area associated with a sports injury of the knee joint." Therefore, catheters were delivered to these arteries and selective angiography was performed.

[0133] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 ml) was administered to the administration site.

[0134] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 ml) was administered.

[0135] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0136] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and the administration site was identified, and the therapeutic agent (approximately 0.2 ml) was administered.

[0137] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 ml) was administered.

[0138] (3) Results Three months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0139] <Study 6: Treatment of sports injuries of the ankle and / or foot> In patients with sports injuries of the ankle and / or foot, or pain associated with such sports injuries, the administration site of the therapeutic agent was identified by the following method, and treatment with the therapeutic agent of the present invention was carried out.

[0140] (1)Patient The subjects were 56 people who regularly participated in sports and had abnormal findings in the ankle and / or foot. These patients had one of the following conditions: Achilles tendonitis, plantar fasciitis, painful peroneal tendonitis, ankle impingement syndrome, hallux valgus, Morton's neuroma, posterior tibial tendonitis, ankle synovitis, MP arthritis, or other sports-related ankle or foot pain.

[0141] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (such as the inguinal artery), advanced to the popliteal artery, and angiography was performed. The target artery (candidate administration site) for sports injuries of the ankle and / or foot is usually the anterior tibial artery, posterior tibial artery, or peroneal artery, all of which correspond to "arteries supplying the affected area of ​​sports injuries of the ankle and / or foot and / or arteries supplying the painful area associated with sports injuries of the ankle and / or foot." Therefore, catheters were delivered to these arteries and selective angiography was performed.

[0142] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 ml) was administered to the administration site.

[0143] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 ml) was administered.

[0144] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0145] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and the administration site was identified, and the therapeutic agent (approximately 0.2 ml) was administered.

[0146] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 ml) was administered.

[0147] (3) Results Three months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0148] <Test 7: Treatment of sports injuries of the wrist> In the following manner, the administration site of the therapeutic agent was identified in patients suffering from a sports injury of the wrist or pain associated with the sports injury, and treatment with the therapeutic agent of the present invention was carried out.

[0149] (1)Patient The subjects were 20 people who regularly participated in sports and had abnormal findings in the wrist. These patients had one of the following conditions: TFCC injury, tendonitis, scaphoid fracture, wrist synovitis, or other sports-related wrist pain.

[0150] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (inguinal artery, radial artery, etc.), advanced to the popliteal artery, and angiography was performed. The target arteries (candidate administration sites) for sports injuries of the wrist are usually the radial artery, ulnar artery, or interosseous artery, all of which correspond to "arteries supplying the affected area of ​​a sports injury of the wrist and / or arteries supplying the painful area associated with a sports injury of the wrist." Therefore, catheters were delivered to these arteries and selective angiography was performed.

[0151] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 ml) was administered to the administration site.

[0152] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 ml) was administered.

[0153] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0154] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and the administration site was identified, and the therapeutic agent (approximately 0.2 ml) was administered.

[0155] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 ml) was administered.

[0156] (3) Results Three months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0157] <Study 8: Treatment of recurrent muscle strains, stress fractures, delayed fracture healing, and nonunion> Using the following method, the administration site of the therapeutic agent was identified in patients with recurrent muscle strain, stress fracture, delayed healing of fracture, and nonunion, and treatment with the therapeutic agent of the present invention was carried out. Although these symptoms are included in sports injuries, they are not necessarily accompanied by pain.

[0158] (1)Patient The subjects were 12 people with recurrent muscle strain, stress fracture, delayed fracture healing, or nonunion at any site.

[0159] (2) Identifying the administration site of the therapeutic agent and treatment A catheter was inserted from a location where arteries could be accessed (inguinal artery, radial artery, etc.), advanced to the popliteal artery, and angiography was performed. Since the target arteries in recurrent muscle strains, stress fractures, delayed fracture healing, or nonunion differ depending on the location, the arteries thought to supply the affected area (candidate administration sites) were selected, the catheter was delivered, and selective angiography was performed.

[0160] (2-1) If abnormal findings are found When an obvious abnormality was observed as a result of angiography, the site was determined to be the site where the therapeutic agent was administered. Then, the therapeutic agent (approximately 0.2 ml) was administered to the administration site.

[0161] (2-2) If it is unclear whether there are any abnormal findings Even if the angiography results showed no abnormal findings, if the candidate administration site was thought to have the potential to nourish the painful area, one of the particulate embolic substance administration site determination agents (approximately 0.2 ml) was administered.

[0162] If discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be the blood vessel (responsible blood vessel) responsible for the injury or pain, i.e., the administration site. Then, a short time (at least 5 minutes or more after administration) after administration of the particulate embolic substance administration site determination agent, the therapeutic agent (approximately 0.2 ml) was administered to the administration site. Depending on the degree of damage and pain and / or the degree of reduction in abnormalities observed on angiography, the therapeutic agent was administered once or multiple times. When multiple administrations were performed, the administration interval was set to 5 minutes.

[0163] On the other hand, if no discomfort (pain, heat, etc.) occurred in the affected or painful area immediately after administration of the particulate embolic substance administration site determination agent or within 10 minutes after administration, the candidate administration site was determined to be a site not involved in the injury or pain, and no further administration was carried out. In this case, the above step (2) was repeated at another candidate administration site, and the administration site was identified, and the therapeutic agent (approximately 0.2 ml) was administered.

[0164] (2-3) If no abnormal findings are found If no abnormal findings were observed, neither the particulate embolic substance administration site determination agent nor the therapeutic agent was administered, the angiography site was changed, and step (2) above was repeated to identify the administration site, after which the therapeutic agent (approximately 0.2 ml) was administered.

[0165] (3) Results Three months after the completion of treatment, the subjects were asked to rate their pain after treatment using a known pain assessment method (NRS score), with the pain before treatment being considered as "10" and then answer as an integer (0 to 10). As a result, over 80% of patients reported that their symptoms and pain had been reduced by half or more. Furthermore, no serious complications occurred in any of the patients. Regardless of the type of particulate embolic material administration site determining agent, the therapeutic agent was effective at the administration site identified by the determining agent.

[0166] <Reference test: Confirmation of the effectiveness of using a particulate embolic material administration site determination agent> In the same test as above, when it was unclear whether or not there were any abnormal findings based on angiography (corresponding to "(2-2) When it was unclear whether or not there were any abnormal findings"), the therapeutic agent was administered directly to the candidate administration site without administering the particulate embolic substance administration site determination agent. As a result, the evaluation results based on the NRS scores were low, with only about 50% of patients responding that their symptoms and pain had improved by half or less.

Claims

1. A therapeutic agent for sports injuries or pain associated with sports injuries, The therapeutic agent contains a particulate embolic material having an average particle size of 10 μm or more and 500 μm or less, The therapeutic agent is administered to at least the following (site A): (Site A) A site where discomfort occurs in the affected area after administration of a contrast agent liquid having a higher osmotic pressure than blood or an embolic material liquid having a higher osmotic pressure than blood to a candidate administration site located in an artery that nourishes the affected area of ​​a sports injury and / or an artery that nourishes the painful area associated with a sports injury.

2. A therapeutic agent as described in claim 1, wherein the presence or absence of abnormal findings based on imaging of blood vessels at the candidate administration site (site A) is unclear.

3. 1. An agent for determining an administration site of a particulate embolic material for treating a sports injury or pain associated with a sports injury, comprising: the agent comprises a contrast medium liquid having a higher osmolality than blood or an embolic material liquid having a higher osmolality than blood; the agent is administered to a candidate administration site, and when the agent causes discomfort in the affected area, the candidate administration site is determined to be an administration site for a particulate embolic material; the candidate administration site is located in an artery supplying nutrients to the affected area of ​​the sports injury and / or in an artery supplying nutrients to the painful area associated with the sports injury; The particulate embolic material has an average particle size of 10 μm or more and 500 μm or less. An agent for determining the administration site of particulate embolic material.