Preparation of Tolterodine Metabolite Loaded Biodegradable PLGA Microspheres

Biodegradable polymer poly（lactic-co-glycolic acid）（PLGA） was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in the emulsification process. The influences of preparation parameters were investigated. The results indicate that increa- sing PLGA concentration from 15% to 40% made the encapsulation efficiency of 5-hydroxymethyl derivative of tol- terodine（5-HMT） increased from 55.39% to 76.32%, and the particle size increased from 34.33 μm to 70,78 lain. In addition, when homogenization speed increased from 850 r/min to 2300 r/min, both particle size and encapsulation efficiency of microspheres decreased. An increase in the volume of aqueous phase led to higher encapsulation efficiency and bigger particle size. Increasing temperature made encapsulation efficiency and particle size change significantly. While reaction temperature increased from 20 ℃ to 50 ℃, the encapsulation efficiency decreased from 70.44% to 24.07%, and particle size increased from 38.66 μm to 69.38 μm. High reaction temperature（over 40 ℃） may lead to porous surface of microspheres. Porous surface, encapsulation efficiency and particle size influenced on the in vitro release of 5-HMT together.

Efficacy and Safety of Medium-to-long-term Use of Tolterodine Extended Release with or without Tamsulosin in Patients with Benign Prostate Hyperplasia and Larger Prostate Size： A Double-blind, Placebo-controlled, Randomized Clinical Trial

Background： The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release （ER） with or without tamsulosin in patients with benign prostate hyperplasia （BPH） and larger prostate size. Methods： Totally, 152 patients （age ≥50 years） with BPH, International Prostate Symptom Score （IPSS） ≥12, quality-of-life （QoL） score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups （n = 38 in each） to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS （total, storage, and voiding subscales）, QoL, maximum urinary flow rate （Qmax）, and postvoid residual volume （PVR） were collected at baseline, and at weeks 4, 12, and 24. Results： Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS （？7.15, ？12.20, and ？14.66 vs. ？3.51, ？5.78, and ？7.23）, storage IPSS （？3.56, ？5.63, and ？6.66 vs. ？1.52, ？1.21, and ？2.43）, voiding IPSS （？2.88, ？5.10, and ？6.48 vs. ？1.52, ？3.03, and ？2.97）, QoL （？1.21, ？2.40, and ？3.21 vs. ？0.39, ？1.41, and ？1.60）, Qmax （2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s）, and PVR （？17.88, ？26.97, and ？27.89 ml vs. ？12.03, ？11.16, and ？16.73 ml） at weeks 4, 12, and 24, respectively; the differences were all statistically significant （P 〈 0.05）. Adverse events （AEs） were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS （？4.61, ？6.79, and ？5.70）, voiding IPSS （？0.64, ？1.83, and ？1.45）, QoL （？0.69, ？1.21, and ？1.41）, or Qmax（？0.79, 2.83, and 1.11 ml/s）, compared with placebo （all P 〉 0.05）. However, a gradual increase in PVR （10.03, 10.41, and 12.89 ml） and more urinary AEs suggestive of urinary retention （11/38 vs. 4/38） were observed. Conclusion： Medium-to-long-term use of tolterodine ER plus tamsulosin should be recommended in patients with BPH and an enlarged prostate volume.

治疗尿失禁的新药——tolterodine

估计发展中国家有３０多万人患尿失禁症，然而该紊乱症是可以治疗的，且多数可以治愈，但当前可用的治疗剂的有效性和耐受性远远不能令人满意。ｔｏｏｌｔｅｒｏｄｉｎｅ（Ｐｈａｍａｃｉａ＆Ｕｐｊｏｈｎ；Ⅲ期临床）是开发的用于治疗尿激励失禁（ＵＵＩ）和逼尿肌活性过强的一个新的毒蕈碱拮抗剂。