Facile Preparation of Danazol Nanoparticles by High-Gravity Anti-solvent Precipitation （HGAP） Method

The nanoparticles of the hydrophobic drug of danazol with narrow size distribution are facilely prepared by controlled high-gravity anti-solvent precipitation （HGAP） process. Intensified micromixing and uniform nucleation environment are created by the high-gravity equipment （rotating packed bed） in carrying out the anti-solvent precipitation process to produce nanoparticles. The average particle size decreases from 55 μm of the raw danazol to 190 nm of the nanoparticles. The Brunauer-Emmett-Teller （BET） surface area sharply increases from 0.66 m^2·g^-1 to 15.08 m^2·g^-l. Accordingly, the dissolution rate is greatly improved. The molecular state, chemical composition, and crystal form of the danazol nanoparticles remains unchanged after processing according to Fourier transform infrared （FTIR） and X-ray diffraction （XRD）, The high recovery ratio and continuous production capacity are highly appreciated in industry. Therefore, the HGAP method might offer a general and facile platform for mass production of hydrophobic pharmaceutical danazol particles in nanometer range.

In vitro effect of danazol on the cytokine production ofperitoneal macrophages in patients with endometriosis

Objective: To study the effect of danazol in vitro on the cytokine production of peritoneal macrophages in patients with endometriosis. Methods: Peritoneal macrophages were obtained from 14 cases of patients with endometriosis. Danazol at concentration of 10 ng/ml and 100 ng/ml were added to the peritoneal macrophages cultures. The tumor necrosis factor a (TNFα)and interleukin 6 (IL-6) levels of peritoneal macrophage supernatant were detected by enzyme linked immunoassay. Results: Danazol at concentration of 100 ng/ml significantly inhibited TNFα and IL-6 production of peritoneal macrophages in patients with endometriosis. Conclusion: It is suggested that the immunomodulatory effect of danazol may contributed to the efficacy in the treatment of endometriosis.

丹那唑(Danazol)结合睾酮庚酸酯对家兔精子形成的可逆抑制作用

乙炔睾酮的甾体类似物丹那唑作为避孕药已在小鼠、沙土鼠、大鼠、家兔以及男人身上作过试验,也研究了其作用机理,发现丹那唑可抑制精子发生,但也使性欲减退。作者发现,丹那唑与睾酮庚酸酯(TE)合并使用,可使100%的动物发生无精子或严重的精子缺乏,而性欲并不减退。在家兔中此作用完全可逆。15个近亲繁殖的同一年龄组(8～9个月)的新西兰雄性白兔(1.4～1.6kg),每笼一个养在通风良好的房间内,每天口服剂量为15mg/kg

Evaluation of Positive Inotropic Activity Induced bya Danazol Derivative in Isolated Rat Heart Model

There is scarce information about the effects of danazol and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of danazol at the cardiovascular level is very confusing. In order to clarify those phenomena in this study, a danazol derivative was synthesized with the objective of evaluating its activity on perfusion pressure and coronary resistance and comparing this phenomenon with the effect exerted by danazol. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in the absence or presence of danazol and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by danazol derivative was evaluated by measuring left ventricular pressure in the absence or presence of following compounds;flutamide, prazosin, metoprolol, indomethacin and nifedipine. The results showed that danazol derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and danazol. Additionally, other data indicate that the danazol derivative increases left ventricular pressure in a dose-dependent manner;nevertheless, this phenomenon was significantly inhibited by flutamide. These data suggest that danazol derivative induces positive inotropic activity through of the activation androgen receptor.

Effects of Nourishing “Yin”-Removing “Fire” Chinese Herb Mixture on the Expression of GABAB Receptors in Hypothalamus of Precocious Puberty Female Rats

Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P < 0.01). On the day of onset-puberty, LH levels were higher in M than those in N (P < 0.01), while the serum E2 and LH levels of TCM decreased when compared with those of M (P B1 receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P < 0.05) and increased in TCM compared with that of M (P < 0.05);simultaneously, the expression of GABABR1 mRNA in hypothalamus was significantly decreased in M when compared with that of N (P < 0.01) and increased in TCM compared with that of M (P < 0.01). On the day of onset-puberty, the number of GABABR1 immunoreactive cells in medial septum (MS) was decreased in M compared with that in N (P < 0.05) and increased in TCM comparing with that of M (P < 0.05);meanwhile, the mRNA expression of GABABR1 in hypothalamus was decreased in M compared with that in N (P B2 receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.

Clinical Observation on Patients with Endometriosis Treated by Tonifying Kidney and Removing Blood Stasis

Objective: To explore the mechanism of treating endometriosis by tonifying Kidney and removing blood stasis with Neiyixiao recipe, ( , NYXR).Methods: One hundred and three patients of endometriosis were divided randomly into the NYXR group (58 cases, treated with NYXR) and the control group (45 cases, treaed with danazol) and were reviewed for the improvement of clinical symptoms, serum level of FSH, LH, PRL, E2, P and T, humoral and cellular immunity (C3, C4, CD3, CD4, CD8), and plasma prostaglandin after treatment.Results: There was no significant difference in effect between the NYXR group and the control group in relief of dysmenorrhea and degradation of elevated plasma prostaglandin (x2 = 0.71,P >0.05). But there was significant difference between the two groups in curing infertility (x2 = 14.77, P<0. 01), and the effect of NYXR in regulating endocrine and immunity was significantly better than that of danazol.Conclusion: By tonifying Kidney and removing blood stasis, NYXR is multi-effective and being one of effective methods in clinical practice for treatment of endometriosis.