著者

小川泰亮

雑誌

クリニカルファーマシー

巻号頁・発行日

vol.4, pp.40-43, 1988

被引用文献数

1

著者

戸口 始 小川 泰亮 岡田 弘晃 山本 眞樹

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.111, no.8, pp.397-409, 1991-08-25 (Released:2008-05-30)

参考文献数

61

被引用文献数

10 14

---

Leuprorelin (leuprolide, D-Leu6-(des-Gly10-NH2)-LH-RH ethylamide) acetate is a superactive agonist of luteinizing hormone-releasing hormone (LH-RH). We developed once-a-month injectable microcapsules of this agonist by our novel in-water drying method. This depot formulation can release the drug at an apparent zero-order rate over one month with bioerosion of copoly (lactic/glycolic acid) utilized as a wall material of the polycore microcapsules. A dramatic prolonged depression of pituitary-gonadal axis, chemical castration, was achieved by the once-a-month injection in experimental animals ; it expects a reliable effcacy for treating hormone-dependent prostatic, breast cancers and endometriosis. Studies on the dosage design of this new delivery system of leuprorelin are summarized.

著者

小川 泰亮

出版者

日本膜学会

雑誌

膜 (ISSN:03851036)

巻号頁・発行日

vol.20, no.2, pp.149-153, 1995-03-01 (Released:2011-03-04)

参考文献数

10

被引用文献数

1

---

A monolithic microcapsule-depot form using a biodegradable polymer was designed and developed, which constantly releases a super-active agonist of LH-RH, leuprorelin, at a constant rate for about one month following a single injection. Microcapsules containing the drug were prepared by a new preparation technique, modifying the solvent evaporation method. When copoly (lactic/glycolic) acid of copolymer ratio of 75/25 and average molecular weight of 10, 000 was adopted a biodegradable polymer, leuprorelin was eliminated from the injection site in rats at a pseudo-zero order rate for one month after a single subcutaneous or intramuscular injection of the microcapsules. Serum leuprorelin levels were maintained at a steady level in rats and dogs for 4 weeks after an injection, and serum testosterone levels decreased to below the normal level and were maintained at the suppressed level for more than 6 weeks. The results indicate that the microcapsule dosage form is useful for LH-RH therapy of sex hormone dependent diseases.After extended clinical evaluation, the monthly microcapsule-depot form of leuprorelin for treating prostate cancer, endometriosis, precocious puberty, and other sex hormone dependent diseases was approved by health authorities in U.S.A., Europe, and Japan as Lupron®; Depot, Enantone®; Depot, and Leuprin®;, respectively.

著者

小川 泰亮

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.6, no.3, pp.165-170, 1991-05-10 (Released:2009-02-23)

参考文献数

20

被引用文献数

2 2

---

Therapeutic applications of prolonged controlled release parenteral microcapsule systems using biodegradable polymer were discussed. The microcapsule system has advantages as follows : the system can be easily injected with a suspending vehicle and a conventional syringe ; it is not necessary to take the system out of the injection site after the release of all the drug, permitting this system to be injected into the same site chronically ; in many cases, smaller doses than those required in the cases of injecting aqueous solutions are expected to be sufficient with increased pharmacological effects when its system is used. Recently, applications for a highly potent LHRH agonist were reported. The system consisted of a biodegradable polymer, copoly (lactic/glycolic) acid (PLGA), containing a highly potent LHRH agonist termed leuprolide acetate released the drug for one month at a pseudo zero order kinetics. The microcapsules were applied clinically for treatment of prostate cancer, resulting remarkably that the microcapsules effectively reduced the dose of the drug required to up to one-fourth of that needed when an aqueous solution is injected daily. This system provides an ideal delivery of water soluble peptide hormone. Further, limits of this system to apply a drug are discussed.

著者

小川 泰亮

出版者

日本DDS学会

雑誌

Drug delivery system (ISSN:09135006)

巻号頁・発行日

vol.15, no.5, pp.429-436, 2000-09-10

被引用文献数

1 4

---

Microencapsulation techniques, phase separation and solvent evaporation, have been developed for preparation of drug-containing monolithic microcapsules for prolonged release using poly(lactide-co-gtycolide) and copoly(lactic/glycolic) acid. A new technique encapsulating highly water-soluble drugs has been established by modifying the solvent evaporation method using a w/o/w emulsion. The method can completely entrap the highly water-soluble drugs into the microcapsules and can easily prepare the microcapsules in a large scale. The drug releases in a pseudozero order kinetics for several weeks with degradation of the polymers after an initial burst release. Many prolonged release-microcapsules containing water-soluble peptides and proteins were prepared by this method. It is difficult to avoid the initial burst release from the microcapsules containing a water-soluble drug, and a technique to avoid the burst has not been found yet. But an insulin-microcapsule system without the initial burst release has just been presented in the DDS meeting in Japan in this summer. The initial burst problem will be solved in near future.