KR20090103656A - Therapeutic agent for fibromyalgia - Google Patents

Abstract

The present invention provides a therapeutic agent for fibromyalgia syndrome (FMS), and further, a symptom associated with fibromyalgia syndrome, in particular a pain associated with fibromyalgia syndrome.

To this end, the present invention provides a therapeutic agent for fibromyalgia syndrome, and a therapeutic agent for pain associated with fibromyalgia syndrome, and in particular, for treating pain associated with fibromyalgia syndrome, characterized in that it contains elkatonin as an active ingredient.

Description

Fibromyalgia Therapeutic Agents {THERAPEUTIC AGENT FOR FIBROMYALGIA}

The present invention relates to a novel medicament for the treatment of fibromyalgia.

Fibromyalgia, also called fibromyalgia syndrome (FMS for short), is characterized by a systemic strengthening of the perception of stimuli by causing long-lasting pain throughout the body. It is done. The reason for this is that virus infection, cytokine imbalance, chemical poisoning, and endocrine dysfunction are not available at this time. According to the American Rheumatology Society's diagnostic criteria (1990), fibromyalgia can be diagnosed if the tenderness is seen in more than 11 places due to the pain of the whole body lasting more than 3 months and the finger palpation of 18 tenderness points. The symptoms range from complaining of mild pain to harming daily life due to prolonged severe pain, and are often difficult to treat.

In general, FMS patients primarily complain of pain and have been treated with drug therapy. Some standard drug therapies used in the treatment of FMS include prescription drugs such as analgesic drugs, hypnotic sedatives, immunosuppressants, and psychotherapy, but any treatment can be used alone or in combination with the drug. It is difficult to say that it is effective for treatment, and thus no drug therapy for FMS has been established at the present time.

Elcatonin, on the other hand, is a compound that chemically modifies the disulfide bonds at the 1,7 position of natural eel calcitonin, and is 1-butyl acid-7- (L-2-aminobutyl acid) -26-L. Aspartic acid-27-L-valine-29-L-alanine calcitonin. Here, elkatonin is known to have an adaptation to the pain of osteoporosis, but since salmon calcitonin, one of the calcitonins, has no effect on the treatment of FMS (Non-Patent Document 1), the elcatonin is also associated with salmon calcitonin Likewise, the therapeutic effect on FMS was not expected.

[Non-Patent Document 1] Bessette L. et. al. Scand J Rheumatol. 1998; 27 (2): 112-6

An object of the present invention is to provide a therapeutic agent that is superior to the known therapeutic agents of FMS. It is also an object of the present invention to provide a therapeutic agent for diseases associated with symptoms according to FMS, in particular pain associated with FMS.

Examples of natural calcitonin include chicken calcitonin, eel calcitonin, human calcitonin, salmon calcitonin, or pig calcitonin. As described above, salmon calcitonin is known to have no effect on the treatment of FMS (Bessette L. et. Al. Scand J Rheumatol. 1998; 27 (2): 112-6). Therefore, it is believed that other natural calcitonin was not expected to have a therapeutic effect on FMS. However, as a result of earnestly examining the effect of elkatonin on FMS against the above prediction, the present inventors have surprisingly found that the effect of FMS on elkatonin is effective on the treatment effect of FMS, in particular, pain relief. It came to the following. That is, the following are mentioned in this invention.

[1] A therapeutic agent for fibromyalgia containing elcatonin.

[1-2] The fibromyalgia therapeutic agent according to the above [1], which is a therapeutic agent for pain associated with fibromyalgia.

[2] The fibromyalgia therapeutic agent according to the above [1] or [1-2], for use in a patient with osteoporosis.

[3] The fibromyalgia therapeutic agent according to the above [1] to [2], for a patient for which the effect is not obtained by administration of an analgesic adjuvant.

On the other hand, when the term number cited as [1] to [2] appears as a range, and a term having a branch number such as [1-2] is arranged within the range, the branch number such as [1-2] It is also meant that the terms having are also cited. The same applies to the following.

[3-2] The fibromyalgia therapeutic agent according to any one of the above [1] to [3], for a patient whose effect is not obtained with milnacipran or a salt thereof.

[4] The agent for treating fibromyalgia according to any one of [1] to [3-2], for improving urinary back pain.

[4-2] The agent for treating fibromyalgia according to any one of [1] to [3-2], for improving lumbar pain.

[5] The therapeutic agent for fibromyalgia according to any one of [1] to [4-2], for administering three or more times of elkatonin 1 to 7 times a week and 5 to 80 units per week.

[5-2] Among the above-mentioned [1] to [4-2] for lowering the VAS to 50 mm or less by administering three or more times of elkatonin 1 to 7 times a week and 5 to 80 units per week The fibromyalgia therapeutic agent of any one of Claims.

[5-3] The fibromyalgia therapeutic agent according to any one of the above [1] to [4-2], for administering three or more times of elkatonin at least once a week for 5 to 80 units.

[5-4] Any one of the above [1] to [4-2] for reducing VAS to 50 mm or less by administering three or more times of elkatonin at a time of 5 to 80 units once a week The fibromyalgia therapeutic agent of Claim.

[6] The fibromyalgia therapeutics according to any one of [1] to [5-2], which is administered in combination with an selective serotonin noradrenaline reuptake inhibitor.

[7] The method according to any one of [1] to [5-2], which is administered alone or in combination with an optional serotonin noradrenaline reuptake inhibitor after administration of the selective serotonin noradrenaline reuptake inhibitor. Fibromyalgia Treatment.

[8] The fibromyalgia therapeutic agent according to any one of the above [1] to [5-2], wherein a selective serotonin noradrenaline reuptake inhibitor is blended.

[9] The fibromyalgia therapeutic agent according to any one of the above [6] to [8], wherein the selective serotonin noradrenaline reuptake inhibitor is milnacipran or a salt thereof.

[10] The agent for treating fibromyalgia according to the above [9], for administering at least 30 mg of milnacipran or a salt thereof per day.

[11] Use of elcatonin in the manufacture of an agent for treating fibromyalgia according to any one of [1] to [10].

The therapeutic agent of the present invention has the effect of enabling the provision of a therapeutic agent for FMS that is substantially free of side effects, that is, with extremely low or no side effects, furthermore, a therapeutic agent for the symptoms accompanying FMS, in particular a therapeutic agent for pain accompanying FMS. Have

1 is a diagram showing a recording sheet of the VAS measuring method.

FIG. 2 is a view showing Roentgen photographs of the patients shown in the Examples.

3 is a view showing the clinical course of the patient shown in the Examples.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated concretely.

FMS is called fibromyalgia syndrome or fibromyalgia and is the most troublesome cause of extensive and long-lasting pain. FMS is characterized by systemic strengthening of the perception of stimuli. FMS patients exhibit analgesia by mechanisms of both allodynia (pain due to harmless stimulation) and hyperalgesia (increased sensitivity to pain stimulation). Syndromes classified by the American Rheumatology Society criteria include all four quadrant parts of the body, and more than three months of pain along the spinal cord. Pain also occurs at 11 or more of the 18 "tender spots" when pressed with a force of 4 kg or less during palpation (Frederick Wolfe et. Al., Arthritis and Reumatism, vol. 33, No. 2, p160-, 1990). Other symptoms associated with FMS include fatigue, sleep, or memory problems. That is, as a symptom accompanying FMS, pain, fatigue, sleep disorder, or memory disorder are specifically mentioned.

Pain accompanying FMS is associated with various underlying diseases or disorders and can be either acute or chronic. Chronic or stubborn pain often lasts for years or decades. The FMS therapeutic agent of the present invention is exemplified as a medicament aimed at alleviating the symptoms of the FMS, in particular, reducing or alleviating pain of pain, and reducing the number of tenderness points. More preferably, the FMS therapeutic agent of the present invention is exemplified as a medicament for treating the symptoms of FMS. As an aspect which treats the symptoms of FMS, the aspect which makes the number of tenderness points 10 or less is illustrated, 9 or less are preferable, 8 or less are more preferable, and 7 or less are more preferable.

The body part which the FMS therapeutic agent of this invention relieves pain is especially a backache or a back part. That is, the FMS therapeutic agent of the present invention aims to improve back pain and also to improve back pain.

The degree of pain accompanying FMS can be measured and expressed, for example, by a measurement method using a score called a VAS (visual analog scale). The VAS is a 10 cm long horizontal or vertical line, as shown in FIG. 1, which writes "no pain" at the left end (or bottom) and "unbearable pain" at the right end (or head). The patient marks the intensity of pain, if necessary, on the line corresponding to his pain x. This distance is measured from the left end (or bottom) in millimeters, and this is a pain score.

The FMS therapeutic agent of the present invention is not limited to the extent as long as it can reduce pain. However, when the VAS is used as an index, for example, the FMS therapeutic agent can be aimed at lowering to 50 mm or less.

Elkatonin in the FMS therapeutic agent of the present invention is a compound chemically modified to disulfide bonds at the 1,7 position of natural eel calcitonin and is 1-butyl acid-7- (L-2-aminobutyl acid). -26-L-aspartic acid-27-L-valine-29-L-alanine calcitonin is known. Elkatonin can be acquired by a well-known method.

The dose of elcatonin may be appropriately determined in consideration of the subject to be treated, the severity of pain, the method of administration, and the prescription. For example, 1 to 7 times a week and 5 to 80 times a week. The case of administering three or more units of elkatonin is mentioned, The case of administering three or more times of elkatonin of 5 to 80 units per once once a week is mentioned. The upper limit of the dose of elkatonin is exemplified by 80 units or less, preferably 70 units or less, more preferably 60 units or less, still more preferably 50 units or less, and particularly preferably 40 units or less. In addition, 30 units or less are the most preferable, As a minimum, 1 unit or more is illustrated, 3 units or more are preferable, 5 units or more are more preferable, 10 units or more are more preferable, 15 units or more are especially preferable. . And such dose and administration frequency can reduce VAS which is an index of pain mentioned above. As a result of lowering the VAS, the value of the VAS is preferably 90 mm or less, more preferably 80 mm or less, still more preferably 70 mm or less, particularly preferably 60 mm or less, 50 Most preferably, it is mm or less. For example, the FMS therapeutic agent of the present invention is an FMS therapeutic agent for lowering VAS to 50 mm or less by administering three or more times of elkatonin 1 to 7 times a week and 5 to 80 units per week, or The FMS therapeutic agent for reducing VAS to 50 mm or less can be mentioned by administering 3 times or more of elkatonin once a week and 5 to 80 units of elkatonin once. In addition, the administration period of the elkatonin is one day or more is illustrated as a lower limit from the start of administration of elkatonin, 1 week or more is preferable, 2 weeks or more is more preferable, 3 weeks or more is more preferable, Although it is especially preferable that it is 4 weeks or more, 6 weeks or more are the most preferable, and as an upper limit, it will not specifically limit, if it is the administration period in which VAS is 50 mm or less, or the administration period in which the number of tenderness points is 10 or less, For example, 6 months The following are illustrated, 5 months or less are preferable, 4 months or less are more preferable, 3 months or less are more preferable, and 2 months or less are especially preferable.

The FMS therapeutic agent of the present invention can be used in combination with other drugs as long as it does not inhibit the therapeutic effect, and can be administered, for example, in combination with a selective serotonin noradrenaline reuptake inhibitor. Selective serotonin noradrenaline reuptake inhibitors can be called SNRI, and typical SNRI compounds include venlafaxine, duloxetine and milnacipran. Milnacipran is already commercially available antidepressant and is known as F2207, TN-912, dalsifran, midacipran, midalifran, and its chemical name is cis- (±) -2- (aminomethyl) -N, N -Diethyl-1-phenyl-cyclopropanecarboxamide.

The FMS therapeutic agent of the present invention may be administered in combination with a selective serotonin noradrenaline reuptake inhibitor or after administration of a selective serotonin noradrenaline reuptake inhibitor.

As such, the FMS therapeutic agent of the present invention is a composition containing elkatonin, and may be combined with a selective serotonin noradrenaline reuptake inhibitor.

Milnacifran, which is used as a selective serotonin noradrenaline reuptake inhibitor, may also be used in the same manner, and the pharmaceutically acceptable salt is not limited as long as it is a salt formed with a pharmaceutically acceptable acid. Hydrochloride, hydrobromide, nitrate, sulfate, hydrogen sulfate, phosphate, acetate, lactate, succinate, citrate, maleate, tartarate, fumarate, methanesulfonate, p-toluenesulfonate or camphorsulfonate And mandelate salts.

The daily dose of milnacipran when used in combination with the therapeutic agent of the present invention is equal to or higher than the dose at which a therapeutic effect is expressed for FMS and / or symptoms accompanying FMS, and converted into the amount of milnacipran as an active ingredient. Thus, the amount of milnacipran administered to carry out the present invention may be appropriately determined within the above ranges in consideration of the judgment of the subject to be treated, the severity of pain, the administration method, and the prescription. The daily dosage of milnacipran or its salt is illustrated by at least 15 mg, preferably at least 25 mg, more preferably at least 30 mg, still more preferably at least 35 mg, particularly preferably at least 40 mg, 50 more than mg is most preferred. The number of doses may be administered once or in divided doses per day.

The subject of the FMS therapeutic agent containing the elkatonin of the present invention as an active ingredient is not particularly limited as long as it is an FMS patient. Among them, it is particularly effective for FMS patients with osteoporosis, and the effect is obtained by administration of an analgesic adjuvant. It is effectively used in patients who have not been administered, and especially in FMS patients whose effect is not obtained even by administration of milnacipran or its salt.

Examples of ineffective FMS patients include patients who could not lower the VAS even if the drug was administered, or patients who could not treat the symptoms of the FMS even when the drug was administered. desirable. In addition, there are other aspects in which patients who have not been able to treat the symptoms of FMS even with administration of a medicament are preferred. As a patient who could not lower the VAS even if the drug was administered, a patient who could not lower the VAS to 90 mm or less even if the drug was administered is exemplified, and a patient who could not lower the 80 mm or less, preferably lowered to 70 mm or less Patients who were absent are more preferred, patients who could not descend below 60 mm are more preferred, patients who could not descend below 60 mm are particularly preferred, patients who could not descend below 50 mm are most preferred.

The analgesic supplements include oriental medicines such as Danggui Paksan, Danggui Sagagao Water Ginseng Tangtang, or Yumimihwan, Meloxycam, Neurotropin, Mecobalamin, Milnacifran, or salts thereof. Can be.

In addition, FMS patients whose effect is not obtained even by administering Milnaciran or its salts include FMS patients who received 30 mg or less of Milnacifran or its salts per day, and 25 mg or less of Wheat per day. Preferred are patients with FMS who have received nasifran or a salt thereof.

The present invention also provides a method for treating pain associated with FMS in a target animal, including a human, and specifically, by administering an effective amount of elkatonin to a subject patient suffering from pain associated with FMS, It is a way to treat the accompanying pain.

The aqueous solution containing elkatonin as an active ingredient is not particularly limited as long as it contains an effective amount of elkatonin, but is preferably an aqueous solution having a suitable pH. As the solvent, known buffers such as citric acid buffer and acetic acid buffer can be used, and pH is preferably 5 to 7, more preferably pH 5 to 6. These concentrations are preferably 0.05 mmol or more, for example, more preferably 0.1 mmol or more. Although an upper limit is not specifically limited, Usually 20 millimolar concentration or less, Preferably 1 millimolar concentration or less is mentioned.

Specifically, it contains one or two or more compounds selected from the group consisting of monocarboxylic acids such as acetic acid, lactic acid, L-histidine and / or water-soluble salts thereof, and the concentration thereof is 0.05-20 mmol, pH Polyhydric carboxyl such as solvent (Japanese Patent Laid-Open No. Hei 2-174726), succinic acid, tartaric acid, or citric acid and / or water solubility thereof, adjusted to 5.0 to 6.5 and ionic strength to mu = 0.01 to 0.5. And a solvent containing one or two or more compounds selected from the group consisting of salts and adjusting their concentrations to 0.05 to 20 mmol, pH to 5.0 to 6.5 and ionic strength to mu = 0.01 to 0.5. In addition, sodium hydroxide, hydrochloric acid, etc. can be used for adjustment of pH as needed. In addition, gelatin may be contained in an amount of 0.01 to 20 w / v% as needed, or an isotonicity agent, procaine hydrochloride, xylocaine hydrochloride, benzyl alcohol, phenol, or the like, a stabilizer, absorption accelerator, preservative, polysorb Surfactants, such as bait, polyoxyethylene, glycerin, and macrogol, can be added.

In addition, as a density | concentration of elcatonin, the thing of 10 unit-80 unit / mL can be used, for example.

Examples of the FMS therapeutic agent of the present invention include FMS therapeutic agents that can be administered by combining elkatonin and selective serotonin noradrenaline reuptake inhibitors. After administration of the selective serotonin noradrenaline reuptake inhibitor, the combination of elkatonin and the selective serotonin noradrenaline reuptake inhibitor or the administration of elkatonin alone is exemplified, and the selective serotonin noradrenaline reuptake inhibitor After administration, it is preferable to administer in combination elkatonin and a selective serotonin noradrenaline reuptake inhibitor. In addition, there is another embodiment in which it is preferable to administer elkatonin alone after the selective serotonin noradrenaline reuptake inhibitor is administered.

Examples of preferred pharmaceutical formulations for the present invention are sustained release preparations, for example sustained release preparations by subcutaneous injection, intramuscular injection, intravenous injection or intraperitoneal injection, preferably sustained release preparations by subcutaneous injection or intramuscular injection, drip A formulation, a patch, etc. are mentioned. As a sustained release preparation by subcutaneous injection, intramuscular injection, intravenous injection or intraperitoneal injection, for example, poly (D, L-lactide-nose as disclosed in Japanese Patent Publication No. Hei 11-501027 Illustrated is the use of microspheres with biodegradable excipients, such as glycolide) polymers, and the formulation of elcatonin to such dosages. As the drop preparation, the drug in the formulation disclosed in "Japanese Clinical, Vol. 59, No. 9, p. 1789-1793, 2001" was replaced with elkatonin, and elkatonin was prescribed so that the above dose. Is illustrated. As a patch preparation, a fine needle is provided in the adhesive surface to skin, and the patch formulation of the type which a chemical penetrates here is contained, for example, about the patch formulation disclosed in Japanese Patent Publication No. 2004-528900. It is exemplified that the prescription of elkatonin is such a dosage. However, of course, it is not limited to these.

<Example>

The present invention will be described based on examples. The present invention is not limited to the following examples by any means, but the effects of the present invention are explained fully by the following examples.

Formulation Example 1 Formulation Example of FMS Therapeutic Agent Containing Elkatonin

0.544 g of sodium acetate (trihydrate) and 1.8 g of sodium chloride were dissolved in water to obtain a 200 milliliter solution, which was taken up to 1 milliliter and diluted to 200 milliliters with 0.9% (w / v) sodium chloride solution. 0.7 milliliter of 0.002N hydrochloric acid was added and mixed here, and it adjusted to pH 5.5 and ionic strength 0.15. Thus, the elkatonin aqueous solution composition was obtained by melt | dissolving 1.4 mg of elkatonin in 200 milliliters of the obtained solution.

[Example 2]

As the elkatonin, Elcitonin strain 20S dispo (manufactured by Asahi Kasei Pharma Co., Ltd.) could be used.

Example 1

1) Subject: age 73 years, gender female, height 148.5 cm, weight 48.8 kg

History: Visiting medical department due to hypertension, insomnia, and Orthopedic surgeon from April 21, 2006 due to deformed lumbar spine

Current history: During the long-term soil disinfection in a plastic house near home on the same day, there was an appeal that "back pain increased and worsened by exposure to pesticides (chloropicrine)." After that, pain gradually increased, and pain was expressed in the neck, trunk, limbs and body on June 30 of the same year.

Science Findings: The tenderness point by facilitation as FMS was positive in all 18 places.

Oriental Medicine: Relieves cold, cold feet in summer.

Mac: Acupuncture (the first mac that is deeply pressed)

Tongue: Pink dental dents (press marks by teeth at the edge of the tongue)

Abdominal pain: chest pain only (dull pain and pressure in the palate)-subarachnoid (responsiveness and resistance or tenderness of the tooth)-gastric constant (water stagnation in the stomach) +, hypothalamus (upper, lower abdominal aorta pulsation) Palpation)-, abdominal first aid (abdominal rectum muscle strain)-, small abdominal inability (abdominal wall easily collapses when the lower abdomen is pressed by force) ±, small abdominal diameter (hard resistance in the lower abdomen, bloating) +, Small abdomen quickness (tenderness to the left long bone ratio) +

Skin is wet and dizziness due to cold feeling + (lower upper limit)

The blood test did not show any abnormalities.

2) The course of treatment: In addition to Western medical treatment, herbal medicines are widely used together, and for cold and pain in the lower extremities of the present case, from May 19, the same year, 5 g min 2 + Dangwi saenggao lactation The formulation was started from 5 g min 2 / day of gingertang.

Cold feeling in the lower limbs improved, but the hot flashes of the face were strong, and the nighttime tendency of insomnia increased and worsened. Since July 14, Meloxycham 10 mg 1T + Dongguk Paksan 5 g min 2 + Yumihwan 5 g min It was changed to 2 / day, and reproduction 100 mL + neurotropin 2A + mecobalamin 500 micrograms 2A / day was combined and administered by drip intravenous injection.

The mild fever continued until mid-June, and tears often appeared until July. On August 11, Yukmihwan improved the burning of the face and coldness of the limbs, but minor improvement of the pain area.

Facial burning was completely lost on August 18th, but over the next half year the symptoms continued to repeat.

Since March 23, 2007, 15 mg 2T / day of milnacipran was administered as it was prone to long-term pain. After that, the symptoms of insomnia and depression were improved, but pain in the trunk and limbs persisted.

On May 11, BMD was 76% (YAM), but mild deformation and atrophy of the spine was observed from X-P (Rentgen photo) findings (FIG. 2). Intramuscular injection of 20 units / week of elkatonin was initiated in the diagnosis of osteoporosis. At this point, 100 mm of VAS was 91 mm.

On May 16, one week after the elkatonin administration, the VAS improved to 85 mm.

On May 18, the patient himself said, "I have improved pain. I can sleep well at night."

On June 2, the improvement was 50 mm in VAS.

On June 8, the patient himself said, "Pain has improved by about half of the time, and current pain is only the back." Even after that, pain was not reached until complete remission, but it was still being administered because elktonin intramuscular injection improved subjective symptoms and improved ADL (Activity of Daily Living) (FIG. 3).

Capture: In the above prescription, each notation represents the following.

"A": represents an ampoule.

"T": Represents a tablet.

"5 g min 2": means that 5 g was prescribed twice.

3) Consideration

From FIG. 3, VAS could be reduced to 50 mm or less in about three weeks after elkatonin administration. Subjects were exposed to pesticides due to prolonged soil disinfection, which resulted in increased back pain.However, when the onset of osteoporosis was started, elkatonin was administered. The pain was improved not only in the back pain but also in the upper limbs and trunk.

In addition, the increase in skin temperature began to be attenuated by the fifth day of intramuscular injection, and the change in skin temperature was consistent with the duration of pain relief.

Thus, by administering elkatonin to the pain of refractory FMS that had no effect with analgesic supplements such as neurotropin, pain other than lumbar pain was alleviated and a significant improvement on VAS was seen. Although FMS has not been found to be a valid treatment until now, it is accompanied by long-lasting pain, and further, lowers ADL. However, it has been found that FMS can be sufficiently effective by the therapeutic agent containing elkatonin of the present invention. Could.

According to the therapeutic agent containing the elkatonin of the present invention, it is possible to treat refractory FMS, and in particular, an effect of improving pain can be expected.

Claims (11)

A therapeutic agent for fibromyalgia containing elcatonin. The agent for treating fibromyalgia according to claim 1, for patients with osteoporosis. The agent for treating fibromyalgia according to claim 1 or 2, wherein the effect is not obtained by administration of an analgesic adjuvant. The agent for treating fibromyalgia according to any one of claims 1 to 3, for improving urinary back pain. The therapeutic agent for fibromyalgia according to any one of claims 1 to 4, for administering three or more times of elkatonin 1 to 7 times a week, 5 to 80 units per week. The therapeutic agent for fibromyalgia according to any one of claims 1 to 5, for administration in combination with a selective serotonin noradrenaline reuptake inhibitor. The therapeutic agent for fibromyalgia according to any one of claims 1 to 5, which is administered in combination with a selective serotonin noradrenaline reuptake inhibitor or after administration alone, after administration of the selective serotonin noradrenaline reuptake inhibitor. The therapeutic agent for fibromyalgia according to any one of claims 1 to 5, wherein a selective serotonin noradrenaline reuptake inhibitor is blended. The therapeutic agent for fibromyalgia according to any one of claims 6 to 8, wherein the selective serotonin noradrenaline reuptake inhibitor is milnacipran or a salt thereof. The fibromyalgia therapeutic according to claim 9, for administering at least 30 mg of milnacipran or a salt thereof per day. Use of elcatonin in manufacture of the fibromyalgia therapeutic agent in any one of Claims 1-10.