JP5314835B2 - Preventive or therapeutic agent for endometriosis - Google Patents

Description

  The present invention relates to a preventive or therapeutic agent for endometriosis.

  Endometriosis is a disease in which endometrium or intima-like tissue expands ectopically at sites other than the inner surface of the uterine cavity. The cause of endometriosis is unknown, and treatments such as surgical removal of adhesions, administration of hormones, administration of analgesics, etc. are performed, but these are all symptomatic treatments and are fundamental treatments There is no way.

  An object of the present invention is to provide a drug effective for the prevention and treatment of endometriosis.

  As a result of intensive studies, the present inventors have found that macrolide antibiotics have preventive and therapeutic effects on endometriosis, and have completed the present invention.

That is, the present invention provides a preventive or therapeutic agent for endometriosis containing a macrolide antibiotic (excluding those having a 14-membered ring or a 15-membered lactone ring) as an active ingredient.

  The present invention provides for the first time an agent effective for the prevention and treatment of endometriosis that can treat endometriosis. Endometriosis is one of the main causes of menstrual pain and infertility due to the rapid increase in the number of patients. Therefore, the present invention greatly contributes to the fields of fertility treatment and menstrual pain treatment and prevention. it is conceivable that.

As described above, the preventive or therapeutic agent for endometriosis of the present invention is effective for both prevention and treatment of endometriosis and has a macrolide antibiotic (having a 14-membered ring or a 15-membered lactone ring. Are excluded as active ingredients. The macrolide antibiotic means a group of antibiotics having a 12 to 16 membered lactone ring (the number of atoms constituting the ring is 12 to 16) and a neutral or amino sugar. Examples of macrolide antibiotics that can be used in the present invention include: Josamycin, Leucomycin group, Spiramycin group, Carbomycin group, Silamycin group, Tylosin, Angoramycin, Kitasamycin, Acetyl Spiramycin, Midecamycin, Rokitamicin, Milosamycin and Maridomycin In addition, hydrated salts, non-toxic salts and derivatives thereof can be mentioned, but are not limited thereto. The term “derivative” as used herein means that the basic skeleton consisting of a lactone ring and a sugar is the same as the original compound, and the substituent bonded to the lactone ring and / or the sugar is changed, and acts as an antibiotic. These derivatives can also be used as long as they have them. Non-toxic salts include hydrochloride, sulfate, tartrate, citrate and the like, but are not limited thereto. As the macrolide antibiotic, one in which two sugars are bonded is preferable.

  The preventive or therapeutic agent for endometriosis of the present invention can be administered by any administration method including oral administration and parenteral administration such as intravenous administration, subcutaneous administration, intramuscular administration, and enteral administration. Oral administration is convenient and preferred. The dose is appropriately set according to the degree of symptoms of the patient and the type of macrolide antibiotic used, but is usually about 300 mg to 500 mg of macrolide antibiotic per day for adults. It is effective at a dose that can be used to treat the disease.

  For the formulation, any formulation method commonly used in the field of pharmaceuticals can be employed. For example, it can be granulated with additives such as polyoxyethylene sorbitan fatty acid ester, propylene glycol or sodium lauryl sulfate, and compressed into tablets, but is not limited thereto. Examples of preparations include, for example, mixing 50 mg of clarithromycin and 34 mg of polyoxyethylene sorbitan fatty acid ester, granulating and tableting into tablets, but of course limited to this is not.

  Since macrolide antibiotics have already been used as therapeutic agents for various infectious diseases, the safety required for pharmaceuticals has been confirmed.

Reference Example 1 Treatment effect of endometriosis with clarithromycin Endometriosis model rats were prepared by the method described in Michael W. Vernon et al., FERTILITY AND STERILITY, Vol. 44, No. 5, November 1985. did. That is, endometriosis model rats were prepared as follows. 8 weeks old Sprague-Dawley rats (female) were acclimated for 12 hours in a light and dark environment for 2 weeks, and then the right uterine horn was removed under general anesthesia with sevoflurane and ketamine hydrochloride, 5 x 5 mm uterine tissue A piece was made and autografted with the endometrial surface facing the peritoneum.

  24 hours after the preparation of endometriosis model rats, commercially available clarithromycin tablets (trade name “Claris Tablets 50 for children” manufactured by Taisho Pharmaceutical Co., Ltd.) are orally administered to endometriosis model rats over 3 days. did. The dose was 10 mg / kg per day in terms of clarithromycin. Controls did not receive clarithromycin. Seven days after the model creation, which is the peak of the model lesion, the peritoneal tissue including the graft was excised to the abdominal muscle, and the lesion material was collected. From these materials, optical microscope specimens (hematoxylin / eosin staining, toluidine blue staining) and electron microscope specimens (uranium / lead heavy staining) were prepared. The extent of the proliferative lesion was observed.

  As a result, mast cell infiltration and stromal proliferative lesions were observed in the control group, but mast cell infiltration was not observed in the clarithromycin administration group, and the degree of stromal proliferative lesions was also clearly suppressed. It was.

Reference Example 2 Therapeutic effect of endometriosis with roxithromycin The same operation as Reference Example 1 except that roxithromycin (trade name “Lurid Tablet 150”, manufactured by Eisai Co., Ltd.) was used instead of clarithromycin. Went. The dose was 6 mg / kg per day in terms of roxithromycin. As a result, mast cell infiltration and stromal proliferative lesions were observed in the control group, but mast cell infiltration was not observed in the roxithromycin administration group, and the degree of stromal proliferative lesions was also clearly suppressed. It was.

Reference Example 3 Treatment effect of endometriosis with azithromycin The same operation as Reference Example 1 was performed except that azithromycin (trade name “Zithromac Tablets 250 mg”, manufactured by Pfizer Pharmaceutical Co., Ltd.) was used instead of clarithromycin. It was. The dose was 10 mg / kg per day in terms of azithromycin. As a result, mast cell infiltration and stromal proliferative lesions were observed in the control group, but mast cell infiltration was not observed in the azithromycin-administered group, and the degree of stromal proliferative lesions was clearly suppressed. .

Claims (1)

A prophylactic or therapeutic agent for endometriosis containing a macrolide antibiotic (excluding those having a 14-membered or 15-membered lactone ring) as an active ingredient.