Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (Ⅱ): classification of tablets disintegration behavior / 中国中药杂志

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅰ): classification of processing routes / 中国中药杂志

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Downregulation of Rho associated coiled-coil forming protein kinase 1 in the process of delayed myocardialization of cardiac proximal outflow tract septum in connexin 43 knockout mice embryo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The connexin43 knockout (Cx43 KO) mouse dies at birth with an enlarged conotruncal region, which leads to the obstruction of the right outflow tract (OFT). Since myocardialization of the proximal OFT septum is one of the key events during heart development, we investigated the process in the Cx43 KO embryo hearts. Rho associated coiled-coil forming protein kinase 1 (ROCK1), is a recently found key molecule to regulate the myocardialization of OFT, but its spatiotemporal expression pattern during myocardialization remains unknown. The objective of this study was to investigate the differentially expressed pattern of ROCK1 between Cx43 KO and wild type embryo hearts, and its relationship with the delayed myocardialization in Cx43 KO embryo hearts.</p><p><b>METHODS</b>Using immunohistochemistry, the processes of myocardiolization were investigated both in Cx43 KO and wild type embryo hearts. The differentially expressed pattern of ROCK1 between Cx43 KO and wildtype embryo hearts was evaluated both at the mRNA and protein level by real-time RT-PCR and immunohistochemistry.</p><p><b>RESULTS</b>The expression of α-sarcomeric actin (α-SCA) in the proximal OFT septum of Cx43 KO embryos was delayed. Meanwhile, it was shown that the downregulation of ROCK1 coincided with delayed myocardialization. The expression of ROCK1 protein was mainly limited to the proximal outflow tract septum from embryo day (E) E11.5 to E15.5. Its expression pattern was similar with that of α-SCA. Real-time RT-PCR found that the expression level of Rock-1 mRNA began at a low level on E11.5 and reached peak at E13.5 and E14.5.</p><p><b>CONCLUSIONS</b>ROCK1 may have an important role in the process of myocardialization of the proximal OFT septum. Downregulation of ROCK1 is likely to contribute to the aberrant myocardialization in Cx43 KO embryo hearts.</p>

Relationship between Apoptosis of Bone Marrow Cells and Tumor Necrosis Factor-?,Fas/FasL Expression in Children with Aplastic Anemia / 实用儿科临床杂志

Objective To investigate the relationship between apoptosis of bone marrow cells and tumor necrosis factor-?(TNF-?),Fas/FasL expression in children with aplastic anemia.Methods The concentration of TNF-? in supernatant of cultured bone marrow mononuclear cell(BMMC) was measured by enzyme linked immunosorbent assay.The expression of Fas/FasL,apoptosis ratio of bone marrow CD34+ cell were evaluated by flow cytometry.Results The concentration of TNF-? in supernatant of cultured BMMC in AA group[SAA (27.9?8.20) ng/L;CAA (23.6?6.78) ng/L] increased significantly compared with control group(t=3.432 P0.05).Apoptosis ratio of CD34+ cell in SAA group[(24.6?9.56)%] and CAA group[(20.9?7.32)%] significantly increased compared with control group(t=3.492,3.458 Pa0.05).The concentration of TNF-? was positively correlated with the expression of CD34+ Fas+ in all types AA children(r=0.542 P0.05).Conclusions TNF-? and Fas/FasL system can be involved in inducing CD34+ cell apoptosis.This may contribute to understanding the decreased number of stem cells and bone marrow failure.

Expression of Fas/FasL in Children with Aplastic Anemia and Its Clinical Significance / 实用儿科临床杂志

Objective To investigate the expression of Fas/FasL in children with aplastic anemia(AA) and its clinical significance.To explore the pathogenesis of AA.Methods CD34+ cell counts and the expression of Fas/FasL in 12 children with severe AA(SAA),18 with chronic AA(CAA)and 10 normal children were detected by flow cytometry combining monocolon antibody.Results The expression of Fas in children with AA were significantly higher than that in control group(P0.05).Conclusions Fas/FasL systeam take part in inducing CD34+ cell apoptosis.This may contribute to understanding the decrease number of stem cells and bone marrow failure.

Expression and Clinical Implications of Preferentially Expressed Antigen of Melanoma Gene in Children with Acute Leukemia / 实用儿科临床杂志

0.05),but the expression in controls were negative.The expression levels of PRAME gene at remission was decreased obviously,but increased again when the patients relapsed.Conclusions Expression of PRAME gene has a high level in childhood acute leukemia.The dynamic changes are closely related with the prognosis.It can be regarded as a candidate for detecting minimal residual disease in acute leukemia,and may have important implications for estimating the prognosis and guiding the chemical therapy.

Mutations of connexin43 in fetuses with congenital heart malformations / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gap junction channels formed by connexin43 (Cx43) protein are important in cardiac morphogenesis, and Cx43 gene is thought to be associated with congenital heart malformation (CHM). This study was undertaken to detect the mutations of Cx43 in fetuses with CHM.</p><p><b>METHODS</b>Cx43 extron DNA was amplified by PCR from 16 fetuses with a variety of CHM. The PCR products were analyzed by SSCP and DNA sequencing. Thirty children who had no CHM were selected as controls.</p><p><b>RESULTS</b>Eight homozygous mutations of Cx43 were observed in a fetus with double outlet right ventricule (DORV), five of the 8 mutations were missense mutations including Arg239Trp, Ser251Thr, Ala253Pro, Pro283Leu and Thr290Asn, and the remaining 3 were silent polymorphisms including Gly252Gly, Pro256Pro and Thr275Thr. No mutations were found in other fetuses and the control group.</p><p><b>CONCLUSIONS</b>Mutations of Cx43 may be associated with congenital conotruncal anomalies. PCR-SSCP is an effective method for screening the mutations of Cx43.</p>

The effect of single chain variable fragment antibody to EC3-4 fragment of desmoglein 3 in a mouse model of pemphigus vulgaris / 中华皮肤科杂志

Objective To study the effect of single chain variable fragment (ScFv) antibody to EC3-4 fragment of desmoglein (Dsg) 3 in a mouse model of pemphigus vulgaris.Methods The ScFv an- tibody to EC3-4 fragment of Dsg-3 was injected subcutaneously into neonatal BALB/c mice at different time points;the mice were then evaluated clinically,histopathologically and by direct immunoflorescence exami- nation for the development of lesions.Results When injected alone,the ScFv antibody did not induce the appearance of key clinical features of pemphigus vulgaris.The antibody also did not prevent the develop- ment of pemphigus vulgaris features induced by sera of patients with pemphigus vulgaris,regardless of the time point of injection of ScFv antibody.Conclusion The ScFv antibody to EC3-4 fragment of Dsg-3 lacks pathogenicity in neonatal BALB/c mice,and also could not inhibit the development of lesions induced by sera from patients with pemphigus vulgaris.