C. Xiaowei, W. Wei, G. Hong, C. Hui, Z. Xiaofei, W. Haonan, W. Yumeng, Z. Xuelan, H. Chunchao
With the developments of science and technology, social development and people's pursuit of quality life, natural and safe skin care products occupied half of the cosmetics industry. In recent years, as synthetic drugs were found that which had toxic and some side effects, people have a tendency to return to nature. Thus, traditional Chinese medicinal plants were applied to natural cosmetics with good efficacy, little side effects and no allergy which had more advantages than synthetic products. The cosmetic products with pure natural ingredients were more and more favored by consumers. Therefore, the article mainly pays attention to the relationship between the active ingredients of Polygonatum sibiricum (PS) and their cosmetic effects, mainly included anti-aging activity, anti-bacteria effect, skin whitening and moisturizing effects. The article will provide more possibilities for research of natural ingredients cosmetics.
{"title":"Review of Polygonatum sibiricum: A new natural cosmetic ingredient.","authors":"C. Xiaowei, W. Wei, G. Hong, C. Hui, Z. Xiaofei, W. Haonan, W. Yumeng, Z. Xuelan, H. Chunchao","doi":"10.1691/ph.2019.9438","DOIUrl":"https://doi.org/10.1691/ph.2019.9438","url":null,"abstract":"With the developments of science and technology, social development and people's pursuit of quality life, natural and safe skin care products occupied half of the cosmetics industry. In recent years, as synthetic drugs were found that which had toxic and some side effects, people have a tendency to return to nature. Thus, traditional Chinese medicinal plants were applied to natural cosmetics with good efficacy, little side effects and no allergy which had more advantages than synthetic products. The cosmetic products with pure natural ingredients were more and more favored by consumers. Therefore, the article mainly pays attention to the relationship between the active ingredients of Polygonatum sibiricum (PS) and their cosmetic effects, mainly included anti-aging activity, anti-bacteria effect, skin whitening and moisturizing effects. The article will provide more possibilities for research of natural ingredients cosmetics.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"69 1","pages":"513-519"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74069932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The current study aimed to investigate the inhibitory effect and mechanism of ensartinib on adhesion, invasion and migration of non-small cell lung cancer (NSCLC) cells, including H460 and A549. Cell adhesion test, scratch test and Transwell cell invasion test were used to detect cell adhesion, migration and invasion. RT-PCR was used to detect the expression of MMP-2 and MMP-9 in H460 and A549 cells. Western blot was used to detect the expression of MMP-2 and MMP-9 proteins, ERK signaling pathway related proteins and p-Akt. Our data showed that ensartinib inhibited adhesion, invasion and migration of H460 and A549 cells in a concentration-dependent manner (P < 0.05). Ensartinib decreased the expression of MMP-2 and MMP-9 in H460 and A549 cells (P < 0.01). It also downregulated the expression of MMP-2 and MMP-9 in H460 and A549 cells, and inhibited the expression of Ras, p-c-Raf, p-ERK 1/2 and p-Akt upstream in a concentration- and time-dependent manner. Ensartinib inhibits the adhesion, invasion and migration of NSCLC cells, and such effect is related to downregulation of MMP-2 and MMP-9 expression, inhibition of ERK signaling pathway and p-Akt expression.
{"title":"Effects and mechanism of ensartinib (X-396) on the adhesion and metastasis of non-small cell lung cancer cells.","authors":"Bin Zhang, T. Qiao, Caixia Gao","doi":"10.1691/ph.2019.9461","DOIUrl":"https://doi.org/10.1691/ph.2019.9461","url":null,"abstract":"The current study aimed to investigate the inhibitory effect and mechanism of ensartinib on adhesion, invasion and migration of non-small cell lung cancer (NSCLC) cells, including H460 and A549. Cell adhesion test, scratch test and Transwell cell invasion test were used to detect cell adhesion, migration and invasion. RT-PCR was used to detect the expression of MMP-2 and MMP-9 in H460 and A549 cells. Western blot was used to detect the expression of MMP-2 and MMP-9 proteins, ERK signaling pathway related proteins and p-Akt. Our data showed that ensartinib inhibited adhesion, invasion and migration of H460 and A549 cells in a concentration-dependent manner (P < 0.05). Ensartinib decreased the expression of MMP-2 and MMP-9 in H460 and A549 cells (P < 0.01). It also downregulated the expression of MMP-2 and MMP-9 in H460 and A549 cells, and inhibited the expression of Ras, p-c-Raf, p-ERK 1/2 and p-Akt upstream in a concentration- and time-dependent manner. Ensartinib inhibits the adhesion, invasion and migration of NSCLC cells, and such effect is related to downregulation of MMP-2 and MMP-9 expression, inhibition of ERK signaling pathway and p-Akt expression.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"76 1","pages":"543-546"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80548442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Behnisch‐Cornwell, G. Laubenstein, P. Bednarski
Glutathione peroxidase (GPx), an important antioxidative enzmye, can be inhibited by various thiols, including of tiopronin and mercaptosuccinic acid (MSA). Recently, there has been discussion regarding the combination of tiopronin in anticancer therapy to overcome acquired resistance to anticancer drugs. However, thiols are also known to act as antioxidants, which can be contraindicated in cancer chemotherapy. This article focuses on the inhibitory effects of tiopronin and MSA on bovine and human glutathione peroxidase activities, and their effects on the redox status of cancer cells. IC50 values for the inhibition for the bovine erythrocyte enzyme were 356 and 24.7 μM for tiopronin and MSA, respectively, with the corresponding Ki values of 343 μM and 14.6 μM, respectively at pH 7.4 and 25 °C. MSA inhibited human GPx activity in human cancer cell lysates at its IC50 while tiopronin did not. Both compounds were cytotoxic to human cancer cell lines GUMBUS and HL-60, with IC50 values between 42.7 and 149.4 μM. Neither had an effect on cell cycle. Only MSA induced apoptosis in HL-60 cells but not in GUMBUS cells, while tiopronin resulted in no apoptosis in either cell line. Combination studies of the MSA with hydrogen peroxide in living cells enhanced the production of reactive oxygen species in GUMBUS cells while tiopronin acted as antioxidant in HL-60 cells. MSA and tiopronin antagonized the cytotoxic effect of cisplatin, doxorubicin and methotrexate in combination studies. Our findings indicate that the antioxidant properties of both thiols prevail over their GPx inhibitory activity in human cancer cell lines.
{"title":"Studies of the inhibitory activities of tiopronin and mercaptosuccinic acid on glutathione peroxidase and their cytotoxic and antioxidant properties.","authors":"S. Behnisch‐Cornwell, G. Laubenstein, P. Bednarski","doi":"10.1691/ph.2019.9472","DOIUrl":"https://doi.org/10.1691/ph.2019.9472","url":null,"abstract":"Glutathione peroxidase (GPx), an important antioxidative enzmye, can be inhibited by various thiols, including of tiopronin and mercaptosuccinic acid (MSA). Recently, there has been discussion regarding the combination of tiopronin in anticancer therapy to overcome acquired resistance to anticancer drugs. However, thiols are also known to act as antioxidants, which can be contraindicated in cancer chemotherapy. This article focuses on the inhibitory effects of tiopronin and MSA on bovine and human glutathione peroxidase activities, and their effects on the redox status of cancer cells. IC50 values for the inhibition for the bovine erythrocyte enzyme were 356 and 24.7 μM for tiopronin and MSA, respectively, with the corresponding Ki values of 343 μM and 14.6 μM, respectively at pH 7.4 and 25 °C. MSA inhibited human GPx activity in human cancer cell lysates at its IC50 while tiopronin did not. Both compounds were cytotoxic to human cancer cell lines GUMBUS and HL-60, with IC50 values between 42.7 and 149.4 μM. Neither had an effect on cell cycle. Only MSA induced apoptosis in HL-60 cells but not in GUMBUS cells, while tiopronin resulted in no apoptosis in either cell line. Combination studies of the MSA with hydrogen peroxide in living cells enhanced the production of reactive oxygen species in GUMBUS cells while tiopronin acted as antioxidant in HL-60 cells. MSA and tiopronin antagonized the cytotoxic effect of cisplatin, doxorubicin and methotrexate in combination studies. Our findings indicate that the antioxidant properties of both thiols prevail over their GPx inhibitory activity in human cancer cell lines.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"47 1","pages":"536-542"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81043556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebuilding, stabilizing and maintaining the dermal lipid barrier is an encouraging disease management concept (relief and care) in the treatment and prevention of atopic dermatitis. Prevention and topical treatment, however, lack a simple, safe, effective and modular approach. For decades, the mainstay of topical therapy of atopic dermatitis has been corticosteroids, with innovations being rare. Our case report demonstrates the struggle of a patient with little relief of itchy dermal lesions and the recurrence of skin lesions following current therapeutic guidelines which proved to be ineffective. Therefore we decided to try an advanced C16-ceramide pathomechanism derived topical therapeutic measure since it offers hope of re-establishing skin and alleviating suffering. Amitriptyline in combination with linoleic acid offers a chance to release from dry and itchy skin, mild to moderate atopic dermatitis lesions without known serious adverse effects of topical corticosteroids, while preventing recurrence.
{"title":"Topical use of amitriptyline and linoleic acid to restore ceramide rheostat in atopic dermatitis lesions - a case report.","authors":"M. Blaess, F. Wenzel, R. Csuk, H. Deigner","doi":"10.1691/ph.2019.9484","DOIUrl":"https://doi.org/10.1691/ph.2019.9484","url":null,"abstract":"Rebuilding, stabilizing and maintaining the dermal lipid barrier is an encouraging disease management concept (relief and care) in the treatment and prevention of atopic dermatitis. Prevention and topical treatment, however, lack a simple, safe, effective and modular approach. For decades, the mainstay of topical therapy of atopic dermatitis has been corticosteroids, with innovations being rare. Our case report demonstrates the struggle of a patient with little relief of itchy dermal lesions and the recurrence of skin lesions following current therapeutic guidelines which proved to be ineffective. Therefore we decided to try an advanced C16-ceramide pathomechanism derived topical therapeutic measure since it offers hope of re-establishing skin and alleviating suffering. Amitriptyline in combination with linoleic acid offers a chance to release from dry and itchy skin, mild to moderate atopic dermatitis lesions without known serious adverse effects of topical corticosteroids, while preventing recurrence.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"38 1","pages":"563-565"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78517650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The potential uses of lyophilized cell free supernatant (CFS) of human oral derived Lactobacillus paracasei SD1 and Lactobacillus rhamnosus SD11 as cosmeceutical ingredients were investigated in the present study. Lyophilized CFS of both strains showed the antioxidant activity in concentration dependent manner. They also exhibited antimicrobial activity against P. acne, S. aureus and S. epidermidis. In combination, these two strains produced synergistic responses, not only on antioxidant activity but also on antimicrobial activity. A liposomal delivery system was employed to mask the unpleasant colour and odour of CFS. The optimal liposome formulation was characterized by a particle size of 344 nm, PDI of 0.19, zeta value of -48.05 mV and %EE of 69.45. The cytotoxicity results showed that the lyophilized CFS, which was toxic, became non-toxic after encapsulating into liposomes. Altogether, current findings demonstrate the worthiness of development of liposomes of probiotic's lyophilized CFS for cosmeceutical applications.
研究了人口服源性副干酪乳杆菌SD1和鼠李糖乳杆菌SD11冻干无细胞上清液作为药妆原料的潜在用途。冻干后两菌株的抗氧化活性均呈浓度依赖性。对痤疮假单胞菌、金黄色葡萄球菌和表皮假单胞菌均有抑菌活性。这两种菌株在抗氧化活性和抗菌活性上均产生协同效应。采用脂质体递送系统来掩盖CFS令人不快的颜色和气味。最佳脂质体的粒径为344 nm, PDI为0.19,zeta值为-48.05 mV, EE %为69.45。细胞毒性实验结果显示，冻干后的CFS，原本是有毒性的，包封在脂质体中后变为无毒性。总之，目前的研究结果证明了益生菌冻干CFS脂质体用于药妆应用的价值。
{"title":"Liposomes of probiotic's lyophilized cell free supernatant; a potential cosmeceutical product.","authors":"M. Htwe, R. Teanpaisan, P. Khongkow, T. Amnuaikit","doi":"10.1691/ph.2019.9030","DOIUrl":"https://doi.org/10.1691/ph.2019.9030","url":null,"abstract":"The potential uses of lyophilized cell free supernatant (CFS) of human oral derived Lactobacillus paracasei SD1 and Lactobacillus rhamnosus SD11 as cosmeceutical ingredients were investigated in the present study. Lyophilized CFS of both strains showed the antioxidant activity in concentration dependent manner. They also exhibited antimicrobial activity against P. acne, S. aureus and S. epidermidis. In combination, these two strains produced synergistic responses, not only on antioxidant activity but also on antimicrobial activity. A liposomal delivery system was employed to mask the unpleasant colour and odour of CFS. The optimal liposome formulation was characterized by a particle size of 344 nm, PDI of 0.19, zeta value of -48.05 mV and %EE of 69.45. The cytotoxicity results showed that the lyophilized CFS, which was toxic, became non-toxic after encapsulating into liposomes. Altogether, current findings demonstrate the worthiness of development of liposomes of probiotic's lyophilized CFS for cosmeceutical applications.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"45 1","pages":"462-466"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75050533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaona Shao, Chen Chen, Chun-sheng Miao, Xiaoyan Yu, Xiangjun Li, Jianan Geng, Dongyan Fan, Xu Lin, Zhen Chen, Yan Shi
Purpose: To appraise the curative effect of ginsenoside Rb1 and trigonelline in diabetic nephropathy and to analyze the expression analysis of microRNAs and their target genes during experimental diabetic renal lesions in rats. Methods: Wistar rats were made diabetic by intraperitoneal injection of 55 mg/kg streptozotocin. According to their fasting blood glucose values and initial body weight, diabetic rats were assigned to specific groups and treated as follows: DN group (tap water, n = 10), A group (ginsenoside Rb1, 40 mg/kg, n = 10), B group (trigonelline, 20 mg/kg, n = 10) and the C group (ginsenoside Rb1 and trigonelline, 60 mg/kg, m(ginsenoside Rb1) : m (trigonelline) = 2:1, n = 10). The control group was treated with tap water (n = 10). All rats were gavaged with drugs or tap water once daily for 12 weeks. Results: Renal dysfunction, oxidative stress, and pathological alteration were significantly alleviated by a combination of ginsenoside Rb1 and trigonellin (C group). Some miRNAs were expressed differentially in Con, DN, A and C groups. Results of immunohistochemistry and western blotting showed that Wnt and β-catenin were expressed differentially in Con, DN, and C groups. Conclusion: Ginsenoside Rb1 and trigonelline could prevent the development of diabetic renal lesions by regulating the expression of miR-3550 and further associating with the Wnt/β-catenin signaling.
{"title":"Expression analysis of microRNAs and their target genes during experimental diabetic renal lesions in rats administered with ginsenoside Rb1 and trigonelline.","authors":"Xiaona Shao, Chen Chen, Chun-sheng Miao, Xiaoyan Yu, Xiangjun Li, Jianan Geng, Dongyan Fan, Xu Lin, Zhen Chen, Yan Shi","doi":"10.1691/ph.2019.8903","DOIUrl":"https://doi.org/10.1691/ph.2019.8903","url":null,"abstract":"Purpose: To appraise the curative effect of ginsenoside Rb1 and trigonelline in diabetic nephropathy and to analyze the expression analysis of microRNAs and their target genes during experimental diabetic renal lesions in rats. Methods: Wistar rats were made diabetic by intraperitoneal injection of 55 mg/kg streptozotocin. According to their fasting blood glucose values and initial body weight, diabetic rats were assigned to specific groups and treated as follows: DN group (tap water, n = 10), A group (ginsenoside Rb1, 40 mg/kg, n = 10), B group (trigonelline, 20 mg/kg, n = 10) and the C group (ginsenoside Rb1 and trigonelline, 60 mg/kg, m(ginsenoside Rb1) : m (trigonelline) = 2:1, n = 10). The control group was treated with tap water (n = 10). All rats were gavaged with drugs or tap water once daily for 12 weeks. Results: Renal dysfunction, oxidative stress, and pathological alteration were significantly alleviated by a combination of ginsenoside Rb1 and trigonellin (C group). Some miRNAs were expressed differentially in Con, DN, A and C groups. Results of immunohistochemistry and western blotting showed that Wnt and β-catenin were expressed differentially in Con, DN, and C groups. Conclusion: Ginsenoside Rb1 and trigonelline could prevent the development of diabetic renal lesions by regulating the expression of miR-3550 and further associating with the Wnt/β-catenin signaling.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"14 1","pages":"492-498"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73756163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The first period of the independent state of Latvia lasted from 1918 to 1940. During this period, pharmacy in Latvia had reached a high level of development. The study covers the period after the loss of independence, when the beginning of World War II marked a major crisis in the development of pharmacy in Latvia. The aim of the study was to compile and systematize information available in published and unpublished sources on the impact of the Soviet occupation (1940-1941) on pharmacy in Latvia, which has not been studied before. The main idea of the study was to find evidence that the Soviet occupation decreased the development capacity of Latvian pharmaceutical industry and narrowed its development opportunities. At the same time, the study reflects part of the general political, ideological and economic environment in Latvia over that period. The study is retrospective and descriptive. Materials from Latvian State Historical Archives and the National Archives of Latvia, and publications from the 20th century press of Latvia were used in the study. In one year, the Soviet system attempted to aggressively transform Latvian pharmaceutical industry to match the USSR standards. This meant the destruction of the capitalist system and the free market, as well as the introduction of centralised management. The radical changes were poorly organised and unsuitable candidates were appointed to positions of responsibility. There is evidence that pharmacy in Latvia experienced complete chaos during that period: private enterprises were nationalised, the number of pharmacy professionals decreased, and medical products from abroad were not supplied to the Latvian market. The Latvian population was rescued from total lack of medications by the last major medication purchase from Germany and the Netherlands shortly before the occupation. All the USSR actions in the pharmaceutical industry were coercive. With the occupation of Nazi Germany in the summer of 1941, the Soviet functionaries left the industry. However, in 1945, during the second occupation, the previous procedures were renewed and their results strengthened. It leads to the conclusion that the Soviet political system had an adverse effect on the development of pharmacy in Latvia.
{"title":"Pharmacy in Latvia during the first Soviet occupation (1940-1941).","authors":"S. Lauze, B. Mauriņa, V. Šidlovska","doi":"10.1691/ph.2019.8232","DOIUrl":"https://doi.org/10.1691/ph.2019.8232","url":null,"abstract":"The first period of the independent state of Latvia lasted from 1918 to 1940. During this period, pharmacy in Latvia had reached a high level of development. The study covers the period after the loss of independence, when the beginning of World War II marked a major crisis in the development of pharmacy in Latvia. The aim of the study was to compile and systematize information available in published and unpublished sources on the impact of the Soviet occupation (1940-1941) on pharmacy in Latvia, which has not been studied before. The main idea of the study was to find evidence that the Soviet occupation decreased the development capacity of Latvian pharmaceutical industry and narrowed its development opportunities. At the same time, the study reflects part of the general political, ideological and economic environment in Latvia over that period. The study is retrospective and descriptive. Materials from Latvian State Historical Archives and the National Archives of Latvia, and publications from the 20th century press of Latvia were used in the study. In one year, the Soviet system attempted to aggressively transform Latvian pharmaceutical industry to match the USSR standards. This meant the destruction of the capitalist system and the free market, as well as the introduction of centralised management. The radical changes were poorly organised and unsuitable candidates were appointed to positions of responsibility. There is evidence that pharmacy in Latvia experienced complete chaos during that period: private enterprises were nationalised, the number of pharmacy professionals decreased, and medical products from abroad were not supplied to the Latvian market. The Latvian population was rescued from total lack of medications by the last major medication purchase from Germany and the Netherlands shortly before the occupation. All the USSR actions in the pharmaceutical industry were coercive. With the occupation of Nazi Germany in the summer of 1941, the Soviet functionaries left the industry. However, in 1945, during the second occupation, the previous procedures were renewed and their results strengthened. It leads to the conclusion that the Soviet political system had an adverse effect on the development of pharmacy in Latvia.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"2 1","pages":"505-510"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78986210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. J. Arends, D. Wang, M. Buurman, J. Luten, N. Koper, C. Wolf, M. Scheren
Glatiramer acetate is indicated for the treatment of patients with relapsing forms of multiple sclerosis (RMS). In 2016, an alternative to the originator product was approved in the EU through the hybrid procedure regulatory pathway. This paper reviews the scientifically rigorous and multifaceted program undertaken to demonstrate the equivalence of this glatiramer acetate follow-on product (GTR) and the reference product Copaxone®, which resulted in the EU approval of GTR 20 mg/mL and 40 mg/mL. Establishing therapeutic equivalence for non-biological complex drugs is not trivial and requires a complex and multidisciplinary effort. Ultimately, there is not a single test or study that establishes therapeutic equivalence of two heterogeneous products. Instead, it requires a good understanding of the synthesis process together with a full set of data that includes comparative physicochemical testing, nonclinical in vitro and in vivo studies, and a comparative clinical study to allow for a valid conclusion that two products are therapeutically equivalent. The detailed understanding of glatiramer's synthesis process and its impact on the characteristics of glatiramer, combined with the results of a scientifically rigorous and multifaceted physicochemical and biological characterization program, and the clinical data from the 794-patient Phase III GATE study, demonstrate that GTR and Copaxone are therapeutically equivalent. The data further demonstrate that Synthon's manufacturing process consistently yields drug substance of the same quality as Copaxone and that switching from Copaxone to GTR is safe and well-tolerated.
{"title":"Comparison of Copaxone® and Synthon's therapeutically equivalent glatiramer acetate.","authors":"R. J. Arends, D. Wang, M. Buurman, J. Luten, N. Koper, C. Wolf, M. Scheren","doi":"10.1691/ph.2019.9515","DOIUrl":"https://doi.org/10.1691/ph.2019.9515","url":null,"abstract":"Glatiramer acetate is indicated for the treatment of patients with relapsing forms of multiple sclerosis (RMS). In 2016, an alternative to the originator product was approved in the EU through the hybrid procedure regulatory pathway. This paper reviews the scientifically rigorous and multifaceted program undertaken to demonstrate the equivalence of this glatiramer acetate follow-on product (GTR) and the reference product Copaxone®, which resulted in the EU approval of GTR 20 mg/mL and 40 mg/mL. Establishing therapeutic equivalence for non-biological complex drugs is not trivial and requires a complex and multidisciplinary effort. Ultimately, there is not a single test or study that establishes therapeutic equivalence of two heterogeneous products. Instead, it requires a good understanding of the synthesis process together with a full set of data that includes comparative physicochemical testing, nonclinical in vitro and in vivo studies, and a comparative clinical study to allow for a valid conclusion that two products are therapeutically equivalent. The detailed understanding of glatiramer's synthesis process and its impact on the characteristics of glatiramer, combined with the results of a scientifically rigorous and multifaceted physicochemical and biological characterization program, and the clinical data from the 794-patient Phase III GATE study, demonstrate that GTR and Copaxone are therapeutically equivalent. The data further demonstrate that Synthon's manufacturing process consistently yields drug substance of the same quality as Copaxone and that switching from Copaxone to GTR is safe and well-tolerated.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"74 1","pages":"449-461"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74677380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Agbo, M. Li, Y.-Q. Wang, R. Saahene, J. Massaro, G. Tian
Hexarelin is a synthetic growth hormone-releasing peptide that exerts cardioprotective effects. Regulation of autophagy is known to be cardioprotective so this study examined the role of autophagy and potential regulatory mechanisms in hexarelin-elicited anti-cardiac hypertrophic action in cardiomyocytes subjected to hypertrophy. H9C2 cardiomyocytes were subjected to hypertrophy by angiotensin-II (Ang-II). Autophagic light chain-3 (LC3) and cytoskeletal proteins were determined by immunofluorescence assay. Autophagy was also detected using monodansylcadaverine (MDC) for autophagic vacuole visualization and Cyto-ID staining for autophagic flux measurement. Molecular changes were analysed by Western blotting and qRT-PCR. Apoptosis was evaluated using flow cytometry and TUNEL assay. ATP content and CCK-8 assay were used in assessing enhanced cell survival whilst oxidative stress was analysed by measuring malondialdehyde(MDA) and superoxide dismutase(SOD) levels. Ang-II induced cardiomyocyte hypertrophy, oxidative stress, apoptosis and decreased cell survival, all of which were significantly suppressed by hexarelin treatment which also enhanced autophagy in hypertrophic H9C2 cells. Furthermore, inhibition of hexarelin induced autophagy by 3-methyladenine (3MA) abolished the anti-hypertrophic function of hexarelin and also abrogated the protection of hexarelin against cell survival inhibition and apoptosis. Conversely, the application of autophagy stimulator rapamycin in H9C2 hypertrophic cells inhibited apoptosis, cell survival and reduced cell size as well. Additionally, hexarelin regulated the upstream signalling of autophagy by inhibiting the phosphorylation of mammalian target of rapamycin(mTOR). We propose that hexarelin plays a novel role of attenuating cardiomyocyte hypertrophy and apoptosis via an autophagy-dependent mechanism associated with the suppression of the mTOR signalling pathway.
Hexarelin是一种合成的生长激素释放肽，具有保护心脏的作用。众所周知，自噬的调节具有心脏保护作用，因此本研究探讨了自噬在hexarelin诱导的心肌细胞肥厚抗心肌作用中的作用和潜在的调节机制。血管紧张素- ii (Ang-II)使H9C2心肌细胞肥大。免疫荧光法检测细胞自噬轻链3 (LC3)和细胞骨架蛋白。自噬检测也采用单胺尸体碱(MDC)进行自噬液泡可视化和细胞id染色进行自噬通量测量。Western blotting和qRT-PCR分析分子变化。流式细胞术和TUNEL法检测细胞凋亡。ATP含量和CCK-8测定用于评估增强的细胞存活率，同时通过测量丙二醛(MDA)和超氧化物歧化酶(SOD)水平分析氧化应激。经hexarelin处理后，Ang-II诱导的心肌细胞肥大、氧化应激、凋亡和细胞存活率降低均明显受到抑制，并增强了肥厚性H9C2细胞的自噬。此外，3-甲基腺嘌呤(3MA)抑制hexarelin诱导的自噬，使hexarelin的抗肥厚功能丧失，也使hexarelin对细胞存活抑制和凋亡的保护作用丧失。相反，自噬刺激剂雷帕霉素在H9C2增厚细胞中的应用抑制了细胞凋亡，细胞存活，细胞大小减小。此外，hexarelin通过抑制哺乳动物雷帕霉素靶蛋白(mTOR)的磷酸化调节自噬的上游信号传导。我们提出，hexarelin通过抑制mTOR信号通路的自噬依赖机制，在减轻心肌细胞肥大和凋亡方面发挥了新的作用。
{"title":"Hexarelin protects cardiac H9C2 cells from angiotensin II-induced hypertrophy via the regulation of autophagy.","authors":"E. Agbo, M. Li, Y.-Q. Wang, R. Saahene, J. Massaro, G. Tian","doi":"10.1691/ph.2019.9324","DOIUrl":"https://doi.org/10.1691/ph.2019.9324","url":null,"abstract":"Hexarelin is a synthetic growth hormone-releasing peptide that exerts cardioprotective effects. Regulation of autophagy is known to be cardioprotective so this study examined the role of autophagy and potential regulatory mechanisms in hexarelin-elicited anti-cardiac hypertrophic action in cardiomyocytes subjected to hypertrophy. H9C2 cardiomyocytes were subjected to hypertrophy by angiotensin-II (Ang-II). Autophagic light chain-3 (LC3) and cytoskeletal proteins were determined by immunofluorescence assay. Autophagy was also detected using monodansylcadaverine (MDC) for autophagic vacuole visualization and Cyto-ID staining for autophagic flux measurement. Molecular changes were analysed by Western blotting and qRT-PCR. Apoptosis was evaluated using flow cytometry and TUNEL assay. ATP content and CCK-8 assay were used in assessing enhanced cell survival whilst oxidative stress was analysed by measuring malondialdehyde(MDA) and superoxide dismutase(SOD) levels. Ang-II induced cardiomyocyte hypertrophy, oxidative stress, apoptosis and decreased cell survival, all of which were significantly suppressed by hexarelin treatment which also enhanced autophagy in hypertrophic H9C2 cells. Furthermore, inhibition of hexarelin induced autophagy by 3-methyladenine (3MA) abolished the anti-hypertrophic function of hexarelin and also abrogated the protection of hexarelin against cell survival inhibition and apoptosis. Conversely, the application of autophagy stimulator rapamycin in H9C2 hypertrophic cells inhibited apoptosis, cell survival and reduced cell size as well. Additionally, hexarelin regulated the upstream signalling of autophagy by inhibiting the phosphorylation of mammalian target of rapamycin(mTOR). We propose that hexarelin plays a novel role of attenuating cardiomyocyte hypertrophy and apoptosis via an autophagy-dependent mechanism associated with the suppression of the mTOR signalling pathway.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"1 1","pages":"485-491"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90999847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minitablets are solid oral forms, which, due to their size (1-3 mm), may be easily swallowed by children. The administration of minitablets in a certain number of units allows for flexible dosing for a broad age group of paediatric patients, which is particularly important for modified-release drugs. In this study, enteric-coated minitablets (3 mm) with pantoprazole were developed and compared to conventional tablets (5 mm). Eudragit L 30D 55® and Acryl Eze II® films, which were 50 and 80 μm thick, respectively, were applied using two different fluid bed systems. The increase in the pantoprazole release rate occurred not only due to the application of a thinner film but also due to the reduction in the size of the core independent of the coating apparatus that was used. In contrast to minitablets, the thin film's thickness was insufficient for 5 mm tablets and a loss of gastro-resistance was observed. The insertion of minitablets into a hard gelatine capsule did not affect drug release from the minitablets under in vitro conditions.
微型片剂是固体口服形式，由于其大小(1-3毫米)，可能很容易被儿童吞下。以一定数量单位给药的微型片剂允许对广泛年龄组的儿科患者灵活给药，这对缓释药物尤其重要。在这项研究中，开发了含泮托拉唑的肠溶微型片剂(3mm)，并与常规片剂(5mm)进行了比较。Eudragit L 30D 55®和Acryl Eze II®薄膜分别为50和80 μm厚，应用于两种不同的流化床系统。泮托拉唑释放率的增加不仅是由于应用了更薄的薄膜，而且是由于与所使用的涂层装置无关的核心尺寸的减小。与微型片剂相比，薄膜厚度不足5毫米片剂，胃阻力丧失。在体外条件下，将微片插入硬明胶胶囊中不影响药物的释放。
{"title":"Comparison of the coating process and in vitro dissolution of 3 mm gastro-resistant minitablets and 5 mm gastro-resistant tablets with pantoprazole.","authors":"M. Szczepańska, M. Sznitowska","doi":"10.1691/ph.2019.8180","DOIUrl":"https://doi.org/10.1691/ph.2019.8180","url":null,"abstract":"Minitablets are solid oral forms, which, due to their size (1-3 mm), may be easily swallowed by children. The administration of minitablets in a certain number of units allows for flexible dosing for a broad age group of paediatric patients, which is particularly important for modified-release drugs. In this study, enteric-coated minitablets (3 mm) with pantoprazole were developed and compared to conventional tablets (5 mm). Eudragit L 30D 55® and Acryl Eze II® films, which were 50 and 80 μm thick, respectively, were applied using two different fluid bed systems. The increase in the pantoprazole release rate occurred not only due to the application of a thinner film but also due to the reduction in the size of the core independent of the coating apparatus that was used. In contrast to minitablets, the thin film's thickness was insufficient for 5 mm tablets and a loss of gastro-resistance was observed. The insertion of minitablets into a hard gelatine capsule did not affect drug release from the minitablets under in vitro conditions.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"93 1","pages":"467-470"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83864390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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