Pain relievers

Abstract

To provide means for treating pain in the hands or feet, which can be performed in a safer manner and works by embolizing abnormal capillary vessels.SOLUTION: The present invention provides a treatment agent for pain in the hands or feet, wherein: the pain treatment agent contains a particulate embolizing substance having an average particle size of 10 to 200 μm; the pain treatment agent is injected and administered into an artery in a hand or a foot; and the administration of the pain treatment agent is completed on the basis of confirmation of at least one predetermined phenomenon.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a pain therapeutic agent.

Background Art

[0002] As pain occurring in the hands and feet, those caused by various diseases (Heberden's nodes and plantar fasciitis) are known.

[0003] Although the cause of such hand and foot pain has been unknown for many years, as a result of the study by the present inventor, it has been found that abnormal blood flow due to an increase in abnormal capillaries (known as "moyamoya vessels") is one of the causes (for example, Non-Patent Document 1). Such abnormal capillaries occur along with nerve growth and the like. Based on this, the present inventor has found a method for treating pain by occluding abnormal capillaries by delivering an embolizing substance (imipenem cilastatin particles) to the abnormal capillaries.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, in the method for treating hand or foot pain by occluding abnormal capillaries, there is a further need for a technique that enables safer treatment.

[0006] The present invention has been made in view of the above circumstances, and an object thereof is to provide a means for treating hand or foot pain by occluding abnormal capillaries, which can be more safely implemented.

Means for Solving the Problems

[0007] The inventors of the present invention have discovered that the above problem can be solved in the treatment of hand or foot pain by embolizing abnormal capillaries by setting the end of administration of the embolic substance to a specific timing, and have completed the present invention. More specifically, the present invention provides the following.

[0008] (1) A pain reliever for the hands or feet, The pain treatment agent contains particulate embolic material having an average particle size of 10 μm or more and 200 μm or less. The aforementioned pain-relieving agent is administered by injection into an artery in the hand or foot. The administration of the aforementioned pain medication shall be terminated upon confirmation of one or more of the following conditions (A) through (D): Pain reliever. (A) Heat sensation in the painful area (B) Pain in the site of pain that is different from the pain described above (C) Discoloration of the skin in the painful area (D) Detection of the embolic material in the painful area using X-ray images.

[0009] (2) The pain treatment agent according to (1), wherein the hand is the whole or a part of the hand from the wrist to the fingertips.

[0010] (3) The pain treatment agent according to (1), wherein the hand is the whole or a portion of the shoulder to the wrist.

[0011] (4) The pain treatment agent according to (1), wherein the foot is the whole or a portion of the foot from the ankle to the toes.

[0012] (5) The pain treatment agent according to (1), wherein the foot is the whole or a portion of the hip joint to the ankle.

[0013] (6) The pain is pain resulting from one or more conditions selected from the group consisting of Heberden's nodes, CMC joint osteoarthritis, Bouchard's nodes, trigger finger, plantar fasciitis, Morton's neuroma, and hallux valgus, as described in any of (1) to (5).

[0014] (7) The pain is pain resulting from one or more conditions selected from the group consisting of rheumatoid arthritis, lateral epicondylitis of the humerus (tennis elbow), medial epicondylitis of the humerus (golfer's elbow), medial collateral ligament injury, osteochondritis dissecans, synovial fold disorder of the elbow joint, insufficiency of the epiphyseal plate of the medial epicondyle of the humerus, insufficiency of the epiphyseal plate of the olecranon, stress fracture of the humerus, stress fracture of the radius, stress fracture of the ulna, osteoarthritis of the elbow, synovitis of the elbow joint, carpal tunnel syndrome, TFCC injury, tenosynovitis, gout, Achilles tendinitis, painful accessory navicular bone, synovitis of the ankle joint, osteoarthritis of the knee, patellar tendinitis (jumper's knee), iliotibial band syndrome (runner's knee), pes anserinus bursitis, patellofemoral band syndrome, infrapatellar fat pad inflammation, shin splints, pain after artificial joint replacement surgery, Osgood-Schlatter disease, and stress fracture, as described in any of (1) to (5).

[0015] (8) The pain treatment agent according to any one of (1) to (7), wherein the injection administration is performed in a state in which the blood flow toward the affected area is tilted toward the direction of gravity rather than the horizontal plane. [Effects of the Invention]

[0016] According to the present invention, a safer method for treating pain in the hand or foot is provided, which involves embolizing abnormal capillaries. [Modes for carrying out the invention]

[0017] The following describes embodiments of the present invention, but the present invention is not limited thereto.

[0018] <Pain relievers> The pain treatment agent according to the present invention (hereinafter also referred to as "the treatment agent of the present invention") is a pain treatment agent for the hand or foot, and contains particulate embolic material having an average particle size of 10 μm or more and 200 μm or less, and is used by injection into an artery of the hand or foot, and the administration of the treatment agent is terminated based on the confirmation of one or more of the following (A) to (D). (A) Heat sensation in the painful area (B) Pain in the site of pain that is different from the pain described above (C) Discoloration of the skin in the painful area (D) Detection of embolizing substances at the pain site in the X-ray image of the X-ray

[0019] As described above, the present inventors have developed a method for treating pain in the hands and feet, in which an embolizing substance is injected into abnormal capillaries to clog the abnormal capillaries and normalize blood flow. However, in the conventional method, for some reason, the phenomenon of clogging of abnormal capillaries may be incomplete, or swelling or the like of the affected part may occur, and there is room for improvement in achieving both treatment effect and safety.

[0020] Therefore, as a result of further examination by the present inventors, it has been found that by using the above (A) to (D) as a reference for the timing of completion of administration of the embolizing substance, an appropriate amount of the embolizing substance can be administered to abnormal capillaries, and as a result, the treatment effect of pain in the hand or foot can be safely achieved.

[0021] In the present invention, "treatment of pain" means alleviating or completely curing pain.

[0022] [[ID=..]] [[ID=1..]]

[0023] [[ID=1..]]<000,[[ID=1..]] In the present invention, "hand" includes the whole or part from the shoulder to the fingertips (for example, the whole or part from the shoulder to the wrist, the so-called whole or part of the arm, the whole or part from the wrist to the fingertips).

[0024] In the present invention, "foot" includes the whole or part from the hip joint to the toes (for example, the whole or part from the hip joint to the ankle, the whole or part from the ankle to the toes).

[0025] In the present invention, "pain in the hand or foot" means any pain occurring in the hand or foot, and the pain site and the causative disease of the pain are not particularly limited.

[0026] [[ID=3..]] From the viewpoint of making the therapeutic agent of the present invention more effective, the hand pain may be pain resulting from one or more conditions selected from the group consisting of Heberden's nodes, CMC joint osteoarthritis, Bouchard's nodes, trigger finger, rheumatoid arthritis, lateral epicondylitis of the humerus (tennis elbow), medial epicondylitis of the humerus (golfer's elbow), medial collateral ligament injury, osteochondritis dissecans, synovial fold disorder of the elbow joint, medial epicondyle epiphyseal plate insufficiency of the humerus, olecranon epiphyseal plate insufficiency, humeral stress fracture, radial stress fracture, ulnar stress fracture, osteoarthritis of the elbow joint, elbow synovitis, carpal tunnel syndrome, TFCC injury, and tenosynovitis. These types of pain can be identified through a doctor's diagnosis.

[0027] From the viewpoint of making the therapeutic agent of the present invention more effective, the foot pain may be pain resulting from one or more conditions selected from the group consisting of plantar fasciitis, Morton's neuroma, hallux valgus, rheumatoid arthritis, gout, Achilles tendinitis, painful accessory navicular bone, ankle synovitis, osteoarthritis of the knee, patellar tendinitis (jumper's knee), iliotibial band syndrome (runner's knee), pes anserinus bursitis, patellofemoral band syndrome, infrapatellar fat pad inflammation, shin splints, pain after artificial joint replacement surgery, Osgood-Schlatter disease, and stress fractures. These types of pain can be identified through a doctor's diagnosis.

[0028] The composition of the therapeutic agent of the present invention will be described in detail below.

[0029] (embolic material) The embolic material used is a particulate substance with an average particle size of 10 μm to 200 μm.

[0030] In this invention, "embolic substance" refers to a substance that can block blood flow in an artery.

[0031] The average particle size of the embolic material can be adjusted as appropriate depending on the diameter of the artery to be embolized.

[0032] From the viewpoint of ensuring that the embolic material has a favorable embolic effect on the target artery, the lower limit of the average particle size of the embolic material is preferably 2 μm or larger, and more preferably 5 μm or larger.

[0033] The upper limit of the average particle size of the embolic material is preferably 100 μm or less, more preferably 50 μm or less, from the viewpoint of avoiding the blockage of unintended arteries other than abnormal capillaries and facilitating delivery to the target artery for embolization.

[0034] In this invention, "average particle size" refers to the average value of the particle size distribution and is determined by a laser diffraction particle size distribution analyzer (for example, the "SALD" series, manufactured by Shimadzu Corporation).

[0035] The shape of the embolic material is not particularly limited, but it may be amorphous, spherical, angular, etc.

[0036] The embolic material is not particularly limited as long as it can block blood flow in the arteries and does not have harmful effects on the body.

[0037] Examples of materials used as embolic agents include those that are poorly soluble in blood at body temperature (e.g., 35-39°C), specifically imipenem and cilastatin. However, to prevent the possibility of the embolic material becoming lodged in a normal blood vessel and blocking it, the embolic material may be a material that is temporarily poorly soluble in blood at body temperature (e.g., 35-39°C) and eventually dissolves in blood at body temperature.

[0038] (Form of therapeutic agent) The therapeutic agent of the present invention is an agent used by injection into an artery in the hand or foot. Therefore, the therapeutic agent of the present invention may, as necessary, contain an embolic substance along with a medium that can be administered into a living artery (physiological buffer solution, sterile water, physiological saline solution, culture medium, contrast agent) or any other component that may be included in the injectable agent, to the extent that it does not impair the embolic effect of the embolic substance.

[0039] The therapeutic agent of the present invention may be in the form of an injectable preparation. The composition of the injectable drug is not particularly limited, but any composition that can be administered to the skin of the target hand or foot using an injection needle can be adopted. Typically, injectable drugs are supplied with an injection needle (such as a Surflo indwelling needle) and a syringe, with the syringe filled with embolic material.

[0040] When administering the therapeutic agent of the present invention, angiography may be performed to identify the administration site of the therapeutic agent. Furthermore, a contrast agent may be used in combination with the embolic substance of the present invention for such imaging. 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., administered simultaneously with the embolic substance), or 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 is not particularly limited, but administering the contrast agent first is preferable from the viewpoint of making it easier to identify the administration site.

[0041] When administering the therapeutic agent of the present invention, after inserting the Surflo indwelling needle into the artery under ultrasound guidance, the procedure may be to confirm the return of blood from the inner needle of the Surflo indwelling needle, then remove the inner needle and connect the outer cannula to a syringe filled with embolic material. Performing a puncture under ultrasound guidance is effective because it can prevent damage to nerves near the artery.

[0042] (Injection site) The therapeutic agent of the present invention is administered to an artery in any hand or foot that can be punctured with an injection needle.

[0043] Examples of arteries in the hand include the brachial artery, radial artery, and ulnar artery.

[0044] Examples of arteries in the leg include the femoral artery (superficial femoral artery, etc.), popliteal artery, posterior tibial artery, and dorsal pedis artery.

[0045] From the perspective of efficiently administering the embolic substance to abnormal capillaries (moyamoya cells), the preferred administration site is an artery that nourishes the painful area. Specifically, an "artery that nourishes the painful area" may be an artery distributed within 10 cm upstream from the painful area.

[0046] If the hand pain is caused by Heberden's nodes, CMC joint osteoarthritis, or trigger finger, it is preferable to administer the drug to an artery located two finger-widths (approximately 4 cm) away from the wrist crease (the thickest crease between the palm and wrist) towards the elbow. Furthermore, areas closer to the wrist crease than the above-mentioned injection site are hypersensitive to stimulation, and there is a higher possibility of developing complex regional pain syndrome (CRPS) due to the stimulation from the injection; therefore, it is preferable not to use these areas as injection sites.

[0047] If the hand pain is due to Heberden's nodes, CMC joint osteoarthritis, Bouchard's nodes, trigger finger, rheumatoid arthritis, lateral epicondylitis of the humerus (tennis elbow), medial epicondylitis of the humerus (golfer's elbow), medial collateral ligament injury, osteochondritis dissecans, synovial fold disorder of the elbow joint, medial epicondyle epiphyseal plate insufficiency of the humerus, olecranon epiphyseal plate insufficiency, humeral stress fracture, radial stress fracture, ulnar stress fracture, osteoarthritis of the elbow joint, elbow synovitis, carpal tunnel syndrome, TFCC injury, or tenosynovitis, the brachial artery that flows into the affected area may be designated as the administration site. When the brachial artery is chosen as the administration site, it is preferable to set the puncture site at the elbow joint level (elbow joint and surrounding area).

[0048] If the foot pain is caused by plantar fasciitis, it is preferable to administer the drug to the posterior tibial artery. In such cases, since blood vessels supply the affected area from very close to the puncture site, it is not necessary to compress the dorsalis pedis artery.

[0049] If the foot pain is caused by Morton's neuroma, it is preferable to administer the embolic agent to either the posterior tibial artery or the dorsalis pedis artery (preferably the larger of the two). In such cases, after puncture, injecting the embolic agent while applying pressure with your fingers to the other artery (i.e., the dorsalis pedis artery if the posterior tibial artery is punctured, or the posterior tibial artery if the dorsalis pedis artery is punctured) makes it easier for the embolic agent to reach the affected area due to the inflow pressure from the opposite side.

[0050] If the foot pain is caused by a bunion, it is preferable to administer the drug into the dorsal pedis artery. In such cases, administering the drug while compressing the posterior tibial artery after puncture makes it easier for the embolic material to reach the affected area.

[0051] If the foot pain is caused by plantar fasciitis, Morton's neuroma, bunions, rheumatoid arthritis, gout, Achilles tendinitis, painful accessory navicular bone, ankle synovitis, osteoarthritis of the knee, patellar tendinitis (jumper's knee), iliotibial band syndrome (runner's knee), pes anserinus bursitis, patellofemoral band syndrome, infrapatellar fat pad inflammation, shin splints, pain after artificial joint replacement surgery, Osgood-Schlatter disease, or a stress fracture, the administration site may be set to an artery that flows into the affected area (such as the superficial femoral artery or other femoral arteries).

[0052] If the foot pain is due to osteoarthritis of the knee, patellar tendinitis (jumper's knee), iliotibial band syndrome (runner's knee), pes anserinus bursitis, patellofemoral band syndrome, infrapatellar fat pad inflammation, shin splints, post-arthritis of the knee, Osgood-Schlatter disease, or stress fracture, it is preferable to set the injection site at the popliteal artery (e.g., the popliteal artery at the knee joint level).

[0053] If the foot pain is due to rheumatoid arthritis, gout, Achilles tendinitis, painful accessory navicular bone, or ankle synovitis, it is preferable to designate the dorsalis pedis artery and / or posterior tibial artery as the administration site.

[0054] When administering embolic substances to the hand or foot, regardless of the administration site or type of disease, it is preferable to administer the substance while the blood flow from the administration site towards the affected area is tilted from the horizontal plane towards the direction of gravity (preferably at an angle of 20° or more, more preferably 45° or more, relative to the horizontal plane). This is because administering in this manner allows the embolic substance, which has a higher specific gravity than blood, and (if used) the contrast agent, to be distributed more efficiently to the affected area by gravity. This effect is particularly preferable in the present invention, which involves injection administration, where the delivery rate to the affected area tends to be lower than that of catheter administration.

[0055] If the affected area is the hand, the following methods can be used to direct blood flow from the injection site towards the affected area in the direction of gravity. • Tilt your entire hand (for example, from wrist to fingertips) towards the direction of gravity rather than the horizontal plane. • Adjust the patient's limb position (joint angles) to tilt the blood vessels in the arms and fingers in the direction of gravity.

[0056] If the affected area is the foot, the following methods can be used to direct blood flow from the injection site towards the affected area in the direction of gravity. • Tilt your entire foot (for example, from ankle to toes) towards the direction of gravity, relative to the horizontal plane. Have the patient assume a prone position. Have the patient lie on their side with the painful area facing downwards. Flex the knee where the pain is occurring.

[0057] Regardless of the type of pain, it is preferable to perform puncture of the injection site (artery) under ultrasound guidance. For example, since the ulnar artery is adjacent to the ulnar nerve and the posterior tibial artery is adjacent to the posterior tibial nerve, performing the puncture under ultrasound guidance can more reliably prevent nerve damage.

[0058] (Dosage, etc.) The administration rate and frequency of the therapeutic agent of the present invention can be appropriately set according to the patient's condition (age, weight, severity of symptoms, etc.). The dosage of the therapeutic agent of the present invention varies depending on the timing of the end of administration as described above, and is not particularly limited.

[0059] (Timing of discontinuation of administration) The present invention is technically characterized by setting the termination point of embolic substance administration to a specific timing. Specifically, after the start of administration of the therapeutic agent of the present invention, administration is terminated based on the confirmation of one or more of the following (A) to (D). (A) Heat sensation in the painful area (B) Pain in the site of pain that is different from the pain described above (C) Discoloration of the skin in the painful area (D) Detection of embolic material in the painful area using radiographic X-ray images.

[0060] "Sensation of heat at the site of pain" means that, after administration of the therapeutic agent of the present invention, the site of pain feels warmer compared to before administration of the therapeutic agent of the present invention. Whether or not a feeling of heat occurred in the painful area can be determined based on the patient's report.

[0061] "Pain different from the aforementioned pain at the site of pain" means that after administration of the therapeutic agent of the present invention, a pain different from the pain that was previously present is felt compared to before administration of the therapeutic agent of the present invention. Examples of such pain include tingling, prickling, and heavy sensations. Whether a different type of pain occurred in the same area as the aforementioned pain can be determined based on the patient's report.

[0062] "Discoloration of the skin at the site of pain" means that, after administration of the therapeutic agent of the present invention, the color of the skin at the site of pain changes compared to before administration of the therapeutic agent of the present invention. Examples of discoloration include becoming pale immediately afterward, followed by a change to red. Whether or not discoloration of the skin in the painful area has occurred can be determined based on its appearance.

[0063] "Detection of embolic material in the painful area using X-ray images" refers to confirming the presence of embolic material in the painful area from X-ray images of the painful area. When performing such detection, it is preferable to use the therapeutic agent of the present invention in combination with a contrast agent.

[0064] The time interval from the point in time when one or more of (A) to (D) is observed to the end of administration of the embolic substance is not particularly limited as long as it is based on the point in time when one or more of (A) to (D) is observed, however, a shorter time interval is preferable from the viewpoint of suppressing side effects. Specifically, it is preferable to discontinue administration immediately after confirming one or more of the phenomena described in (A) through (D). "Immediately after the time when any one or more of (A) to (D) is observed" specifically means preferably within 50 seconds, more preferably within 30 seconds, and more specifically, within 15 seconds, within 10 seconds, or within 5 seconds.

[0065] Furthermore, the administration of the embolic substance may be terminated if any one of the phenomena described in (A) through (D) above is observed, or if two or more phenomena are observed. However, when discontinuing the administration of the embolic substance based on the confirmation of two or more phenomena, it is preferable that the time from the occurrence of the first phenomenon to the occurrence of the last phenomenon be as short as possible (preferably within 1 minute) to prevent excessive dosage.

[0066] The administration of the therapeutic agent of the present invention is terminated by any operation that stops the injection of the therapeutic agent into the administration site. Such operations include, for example, withdrawing the outer barrel of the injection agent from the administration site and applying pressure to stop bleeding.

[0067] <Therapeutic effects of the present invention's therapeutic agent> According to the therapeutic agent of the present invention, pain in the hand or foot can be treated more safely by embolizing abnormal capillaries. For example, with the therapeutic agent of the present invention, by ending the administration of the embolic substance at the timing described above, it is possible to appropriately prevent excessive administration of the embolic substance and the resulting persistent pain, necrotic discoloration, and swelling of the affected area, while still achieving a pain-relieving effect.

[0068] The therapeutic effect of the therapeutic agent of the present invention can be evaluated by any method for assessing pain. Examples of such methods include methods based on the "NRS (Numerical Rating Scale) score" and methods in which patients subjectively report the degree of pain improvement ("Patients Global Impression of Change"). [Examples]

[0069] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0070] <Preparation of embolic materials, etc.> In this example, imipenem cilastatin (trade name "Primaxine," manufactured by Merck & Co.) was used as the embolic material. The average particle size of this embolic material was 70 μm or less, as measured using a laser diffraction particle size distribution analyzer ("SALD" series, manufactured by Shimadzu Corporation). The embolic material was prepared as an aqueous solution at a concentration of 1 g / 10 ml.

[0071] In this example, Iopark (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 active ingredients) was set to 10 cc of contrast agent per 1 g of embolic material.

[0072] <Example 1-1: Treatment of hand pain> In patients with Heberden's nodes (corresponding to hand pain), the following method was used to administer embolic substances and confirm their effects.

[0073] (1) Setting the site of administration of the embolic substance The injection site was set to an artery located two finger-widths (approximately 4 cm) towards the elbow from the wrist crease (the thickest crease between the palm and wrist). This site corresponds to the artery that supplies the painful area. Furthermore, areas closer to the wrist crease than the above-mentioned injection site are hypersensitive to stimulation, and there is a higher possibility of developing complex regional pain syndrome (CRPS) due to the stimulation from the injection; therefore, these areas were not selected as injection sites.

[0074] (2) Puncture of the administration site (artery) The radial and ulnar arteries were observed using ultrasound, and the area around the injection site (artery) was anesthetized under ultrasound guidance. After the anesthetic had taken effect, a Surflo indwelling needle (24G x 19mm) was inserted into the artery under ultrasound guidance. Ultrasound guidance was used because performing the puncture without ultrasound guidance could damage nerves near the artery. In particular, since the ulnar artery is adjacent to the ulnar nerve, performing the puncture under ultrasound guidance was effective in preventing nerve damage. After puncturing the artery, backflow of blood from the inner needle of the Surflo indwelling needle was confirmed. Then, the inner needle was withdrawn and the outer cannula was placed in the artery and connected to a syringe filled with embolic material.

[0075] Furthermore, during the connection of the outer cannula to the syringe, the artery sometimes constricted, resulting in an extremely slow blood return rate. In this case, if the embolic material is administered while the artery is constricted, it can only be delivered to the central part of the artery, and cannot be delivered to the area to be treated (in this case, the finger). Therefore, in this case, the syringe was left attached and the outer barrel was not moved, and the patient waited until the syringe was naturally pushed back by the backflow of blood. This backflow is a sign that the spasm has been released.

[0076] (3) Initiation of administration of embolic substance After connecting the outer barrel to the syringe, the syringe was pushed to begin administration of the embolic material. The embolic material was administered at a rate of 0.2 g / min. During administration, the drug was administered slowly while frequently checking for blood return. This is because if blood return is not checked frequently, there is a risk of administering the drug outside the injection site without realizing that the outer sheath has come off.

[0077] (3) Completion of administration of embolic substance After initiating the administration of the embolic material, the outer sheath was promptly removed, pressure was applied to stop the bleeding, and the administration of the embolic material was terminated as soon as one or more of the following conditions (A) through (D) were observed. (A) Heat sensation at the site of pain (as reported by the patient) (B) Pain in the same area as the pain described above (as reported by the patient) (C) Discoloration of the skin at the site of pain (as observed visually by a doctor) (D) Detection of embolic material in the painful area using radiographic X-ray images.

[0078] In this case, some patients exhibited two or more of phenomena (A) through (D), but the time between the onset of the first phenomenon and the onset of the last phenomenon was short (less than 1 minute), and the administration of the embolic substance was terminated immediately after the onset of the last observed phenomenon.

[0079] (4) Confirmation of treatment effectiveness After administration, the symptoms of Heberden's nodes improved significantly. In this case, imipenem cilastatin was used as the embolic agent and in combination with a contrast agent. However, even when using embolic agents other than imipenem cilastatin, or when not using a contrast agent, good therapeutic effects were achieved by adopting the above administration method and criteria for discontinuing administration.

[0080] Furthermore, by ending the administration of the embolic substance at the timing described above, it was possible to appropriately prevent excessive administration of the embolic substance and the resulting persistent pain, necrotic discoloration, and swelling of the affected area.

[0081] Furthermore, the treatment method described above has shown good therapeutic effects not only for Heberden's nodes, but also for patients with other hand pains (CM joint osteoarthritis, Bouchard's nodes, trigger finger, rheumatoid arthritis, lateral epicondylitis of the humerus (tennis elbow), medial epicondylitis of the humerus (golfer's elbow), medial collateral ligament injury, osteochondritis dissecans, synovial fold disorder of the elbow joint, medial epicondyle epiphyseal plate insufficiency of the humerus, olecranon epiphyseal plate insufficiency, humeral stress fracture, radial stress fracture, ulnar stress fracture, osteoarthritis of the elbow joint, elbow synovitis, carpal tunnel syndrome, TFCC injury, and tenosynovitis, etc.).

[0082] Furthermore, the above effects tended to be enhanced when the blood flow from the administration site towards the affected area was directed in the direction of gravity (for example, by moving the patient's joints to direct the blood vessels in the arms and fingers in the direction of gravity).

[0083] As a comparative example, when the administration of the embolic substance was terminated 20 seconds or more after one or more of the phenomena described in (A) to (D) above had been observed, adverse events such as swelling of the affected area were observed.

[0084] <Example 1-2: Treatment of Hand Pain> Except for setting the administration site of the embolic substance in "(1) Setting the site of administration of the embolic substance," the embolic substance was administered to a patient with lateral epicondylitis of the humerus (tennis elbow) in the same manner as in "Example 1-1" above. The administration site was set at the level of the elbow joint in the brachial artery.

[0085] As a result, the symptoms of lateral epicondylitis of the humerus significantly improved. This effect was observed not only in patients with lateral epicondylitis of the humerus, but also in patients with other hand pains (rheumatoid arthritis, medial epicondylitis of the humerus (golfer's elbow), medial collateral ligament injury, osteochondritis dissecans, synovial fold disorder of the elbow joint, insufficiency of the epiphyseal plate of the medial epicondyle of the humerus, insufficiency of the epiphyseal plate of the olecranon, stress fracture of the humerus, stress fracture of the radius, stress fracture of the ulna, osteoarthritis of the elbow, synovitis of the elbow joint, carpal tunnel syndrome, TFCC injury, and tenosynovitis, etc.).

[0086] Furthermore, the above effects tended to be enhanced when the blood flow from the administration site towards the affected area was directed in the direction of gravity (for example, by moving the patient's joints to direct the blood vessels in the arms and fingers in the direction of gravity).

[0087] <Example 2-1: Treatment of foot pain> In patients with plantar fasciitis (corresponding to foot pain), the following method was used to administer an embolic substance and confirm its effect.

[0088] (1) Setting the site of administration of the embolic substance The posterior tibial artery was chosen as the injection site. This site corresponds to the artery that supplies the painful area.

[0089] (2) Puncture of the administration site (artery) The posterior tibial artery was observed using ultrasound, and the area near the injection site (artery) was anesthetized under ultrasound guidance. After the anesthetic took effect, a Surflo indwelling needle (24G x 19mm) was inserted into the artery under ultrasound guidance. Ultrasound guidance was used because performing the puncture without ultrasound guidance could damage nerves near the artery. In particular, since the posterior tibial artery is adjacent to the posterior tibial nerve, performing the puncture under ultrasound guidance was effective in preventing nerve damage. After puncturing the artery, backflow of blood from the inner needle of the Surflo indwelling needle was confirmed. Then, the inner needle was withdrawn and the outer cannula was placed in the artery and connected to a syringe filled with embolic material.

[0090] Furthermore, during the connection of the outer cannula to the syringe, artery constriction sometimes occurred, resulting in extremely slow blood return velocity. In this case, if the embolic material is administered while the artery is constricted, it can only be delivered to the central part of the artery, and cannot be delivered to the site to be treated (in this case, the peripheral affected area). Therefore, in this case, the syringe was left attached and the outer barrel was not moved, and the patient waited until the syringe was naturally pushed back by the backflow of blood. This backflow is a sign that the spasm has been released.

[0091] (3) Initiation of administration of embolic substance After connecting the outer barrel to the syringe, the syringe was pushed to begin administration of the embolic material. The embolic material was administered at a rate of 0.2 g / min. During administration, the drug was administered slowly while frequently checking for blood return. This is because if blood return is not checked frequently, there is a risk of administering the drug outside the injection site without realizing that the outer sheath has come off.

[0092] (3) Completion of administration of embolic substance After initiating the administration of the embolic material, the outer sheath was promptly removed, pressure was applied to stop the bleeding, and the administration of the embolic material was terminated as soon as one or more of the following conditions (A) through (D) were observed. (A) Heat sensation at the site of pain (as reported by the patient) (B) Pain in the same area as the pain described above (as reported by the patient) (C) Discoloration of the skin at the site of pain (as observed visually by a doctor) (D) Detection of embolic material in the painful area using radiographic X-ray images.

[0093] In this case, some patients exhibited two or more of phenomena (A) through (D), but the time between the onset of the first phenomenon and the onset of the last phenomenon was short (less than 1 minute), and the administration of the embolic substance was terminated immediately after the onset of the last observed phenomenon.

[0094] (4) Confirmation of treatment effectiveness After administration, the symptoms of plantar fasciitis significantly improved. In this case, imipenem cilastatin was used as the embolic agent and in combination with a contrast agent. However, even when using embolic agents other than imipenem cilastatin, or when not using a contrast agent, good therapeutic effects were achieved by adopting the above administration method and criteria for discontinuing administration.

[0095] Furthermore, by ending the administration of the embolic substance at the timing described above, it was possible to appropriately prevent excessive administration of the embolic substance and the resulting persistent pain, necrotic discoloration, and swelling of the affected area.

[0096] Furthermore, the treatment method described above has shown good therapeutic effects not only for plantar fasciitis but also for patients with other foot pains (Morton's neuroma, hallux valgus, rheumatoid arthritis, gout, Achilles tendinitis, painful accessory navicular bone, ankle synovitis, osteoarthritis of the knee, patellar tendinitis (jumper's knee), iliotibial band syndrome (runner's knee), pes anserinus bursitis, patellofemoral band syndrome, infrapatellar fat pad inflammation, shin splints, pain after artificial joint replacement surgery, Osgood-Schlatter disease, and stress fractures, etc.).

[0097] Furthermore, the above effects tended to be enhanced when the blood flow from the administration site towards the affected area was directed in the direction of gravity (for example, by having the patient lie face down, lie on their side with the painful area facing downwards, or flex the painful knee).

[0098] As a comparative example, when the administration of the embolic substance was terminated after one or more of the phenomena described in (A) to (D) above had been observed and more than one minute had elapsed, adverse events such as swelling of the affected area were observed.

[0099] <Example 2-2: Treatment of foot pain> Except for setting the administration site of the embolic substance in "(1) Setting the site of administration of the embolic substance," the embolic substance was administered to a patient with patellar tendinitis (jumper's knee) in the same manner as in "Example 2-1" above. The administration site was set to the popliteal artery at the knee joint level.

[0100] As a result, the symptoms of patellar tendinitis significantly improved. This effect was observed not only in patients with plantar fasciitis, but also in patients with other foot pains (rheumatoid arthritis, gout, Achilles tendinitis, painful accessory navicular bone, ankle synovitis, osteoarthritis of the knee, iliotibial band syndrome (runner's knee), pes anserinus bursitis, patellofemoral band syndrome, infrapatellar fat pad inflammation, shin splints, pain after artificial joint replacement surgery, Osgood-Schlatter disease, and stress fractures, etc.).

[0101] Furthermore, the above effects tended to be enhanced when the blood flow from the injection site towards the affected area was directed in the direction of gravity (for example, by having the patient lie face down).

Claims

1. A pain reliever for the hands or feet, The pain treatment agent contains particulate embolic material having an average particle size of 10 μm or more and 200 μm or less. The aforementioned pain-relieving agent is administered by injection into an artery in the hand or foot. The administration of the aforementioned pain medication shall be terminated upon confirmation of one or more of the following conditions (A) through (D): Pain reliever. (A) Heat sensation at the site of pain (B) Pain in the site of pain that is different from the pain described above (C) Discoloration of the skin in the painful area (D) Detection of the embolic material in the painful area using X-ray images from a radiograph.

2. The pain treatment agent according to claim 1, wherein the hand is the entire or partial hand from the wrist to the fingertips.

3. The pain treatment agent according to claim 1, wherein the hand is the entirety or a portion of the hand from the shoulder to the wrist.

4. The pain treatment agent according to claim 1, wherein the foot is the whole or a portion of the foot from the ankle to the toes.

5. The pain treatment agent according to claim 1, wherein the foot is the entire or partial portion of the hip joint to the ankle.

6. The pain treatment agent according to any one of claims 1 to 5, wherein the pain is pain resulting from one or more conditions selected from the group consisting of Heberden's nodes, CMC joint osteoarthritis, Bouchard's nodes, trigger finger, plantar fasciitis, Morton's neuroma, and hallux valgus.

7. The pain is pain resulting from one or more conditions selected from the group consisting of rheumatoid arthritis, lateral epicondylitis of the humerus (tennis elbow), medial epicondylitis of the humerus (golfer's elbow), medial collateral ligament injury, osteochondritis dissecans, synovial fold disorder of the elbow joint, insufficiency of the epiphyseal plate of the medial epicondyle of the humerus, insufficiency of the epiphyseal plate of the olecranon, stress fracture of the humerus, stress fracture of the radius, stress fracture of the ulna, osteoarthritis of the elbow joint, synovitis of the elbow joint, carpal tunnel syndrome, TFCC injury, tenosynovitis, gout, Achilles tendinitis, painful accessory navicular bone, synovitis of the ankle joint, osteoarthritis of the knee joint, patellar tendinitis (jumper's knee), iliotibial band syndrome (runner's knee), pes anserinus bursitis, patellofemoral band syndrome, infrapatellar fat pad inflammation, shin splints, pain after artificial joint replacement surgery, Osgood-Schlatter disease, and stress fractures, according to any one of claims 1 to 5.

8. The pain treatment agent according to any one of claims 1 to 7, wherein the injection administration is performed in a state in which the blood flow toward the affected area is tilted toward the direction of gravity rather than the horizontal plane.