Objective To provide medical institutions with occupational exposure risk prevention and control strategies for cytotoxic drugs.Enhance the protective awareness of medical personnel and reduce potential occupational exposure risks. Methods The World Health Organization (WHO) guideline formulation manual was used to study and design the guidelines for the hierarchical control and protection of occupational exposure to cytotoxic drugs.Guide writing group collect exposure risk problems in various links such as the allocation and use of cytotoxic drugs after entering the hospital retrieval through systematic retrieval.The Delphi method was used to construct identify clinical issues, and evidence-based research methods were used to develop relevant evidences.The Delphi method was used to survey experts and identify clinical issues.Literature research and expert experience methods were utilized to compile relevant evidences.Quality evaluation was conducted using the GRADE method, and consensus was reached on the recommendation opinions and evidence levels through Delphi method.Ultimately,the “Guidelines for Prevention and Control of Occupational Exposure Risks to Cytotoxic Drugs in Medical Institution” was formulated. Results Through the online questionnaire survey of 143 experts, the Delphi method was used to reach a consensus on the guidelines.By combining engineering control, administrative control and personal protective equipment at different levels, a graded control approach was established.A total of 37 clinical issues were finally determined through hierarchical management and control, resulting 36 recommendations. Conclusion The guidelines covers seven steps after cytotoxic drugs enter the hospital, including transportation, reception, storage, unpacking, dispensing, finished product use, and waste treatment,which provide reference for medical institutions to develop cytotoxic drugs related prevention and control measures.Therefore, the possibility of occupational exposure to cytotoxic drugs could be reduced and the safety of medical personnel could be protected.
Objective To determine the chemosensitization effect of trichosanthin (TCS)and cisplatin on cervical cancer HeLa cells,and preliminarily explore its mechanism. Methods The effects of TCS and cisplatin alone or in combination on the proliferation of cervical cancer HeLa cells were detected by CCK8 assay.The combination index (CI)of TCS and cisplatin was detected by CompuSyn software.The effects of drugs on cell migration were detected by wound healing assay and transwell assay.The effect of drugs on cell apoptosis was detected by flow cytometry.The effect of drugs on the expression levels of apoptosis-related proteins in HeLa cells was analyzed by Western blotting. Results TCS and cisplatin alone could inhibit the proliferation of cervical cancer HeLa cells,and the combination of TCS and cisplatin showed more potent inhibition.The sensitization index of TCS to cisplatin was 3.04.The CI values of TCS and cisplatin after 48 h treatment were all less than 1 in a concentration-dependent manner (P<0.05).Cell scratch test and Transwell method showed that the combination group could significantly inhibit the migration of HeLa cells compared with the single drug group (P<0.05).Flow cytometry results showed that the apoptosis rate of HeLa cells increased in the combination therapy group compared with the single therapy group (P<0.05).Western blotting assay showed that compared with the single drug group,the combination drug up-regulated the expression of pro-apoptotic proteins Bax and C-PARP,and down-regulated the expression of apoptotic inhibitory protein Bcl-2 (P<0.05). Conclusions TCS combined with cisplatin has a synergistic effect on inhibiting the growth of cervical cancer HeLa cells.TCS can sensitize HeLa cells to cisplatin by chemotherapy,and the mechanism may be related to the increment of HeLa cell apoptosis and inhibition of migration.
Objective To systematically study the solvatomorphism of 7- hydroxyisoflavone and to provide a scientific basis for the quality control of the solvated polymorphic impurities in this drug. Methods By analyzing the structure characteristics,crystal packing, and interactions of the obtained 7-hydroxyisoflavone solvates,two new solvates of 7-hydroxyisoflavone were prepared by mechanical chemical method.Single crystal X-ray diffraction,powder X-ray diffraction,differential scanning calorimeter,thermo gravimetric analysis and infrared spectroscopy were used to characterize the solvates.Furthermore,the stability of solvates was investigated. Results The two new solvates of 7- hydroxyisoflavone prepared in this work were all metastable crystal forms. Conclusion The metastable crystal forms can be prepared by mechanical chemical methods,providing new materials and technical support for enriching the types and the quality control of crystal forms.
Objective To prepare an amorphous sorafenib system,to evaluate its crystallization dynamic stability,and to discuss the inhibition effect of polymers on amorphous crystallization. Methods Amorphous sorafenib was prepared by the rotary evaporation method.The amorphous forming ability and crystallization kinetics stability of amorphous sorafenib were studied by non-isothermal multi-rate differential scanning calorimetry.The inhibitory effects of polymers on amorphous sorafenib crystallization were investigated by solubility and dissolution experiments in vitro. Results The kinetic fragility index was 48.The ratio of glass transition temperature to melting temperature was about 0.8.The reduced crystallization temperature was 0.51.The crystallization activation energy was 152.15 kJ·mol-1.Avrami index was about 2.In 50 μg·mL-1 methyl cellulose solution,the solubility and cumulative dissolution of the amorphous system were 1.43 and 2.17 times that of the pure amorphous drug,respectively. Conclusion Amorphous sorafenib has high crystallization dynamic stability.Methyl cellulose prolongs the supersaturation time of amorphous sorafenib.
Objective To prepare and analyze phloretin-4,4'-bipyridine cocrystal,and to detect the solubility of the cocrystal. Methods A new cocrystal of phloretin with 4,4'-bipyridine(BPY)was prepared through liquid-assisted grinding,slurry crystallization,and evaporative crystallization.The cocrystal was characterized by powder X-ray diffraction,thermogravimetric analysis-differential scanning calorimetry,Fourier transform infrared spectrometer,and elemental analysis.The dissolution rate,equilibrium solubility,and stability of cocrystal samples were analyzed. Results The phloretin-4,4'-bipyridine cocrystal with higher purity was prepared in liquid-assisted grinding,slurry crystallization,and evaporative crystallization.The ratio of the amount of molecular substance was 1:1.The dissolution behavior of the cocrystal in three kinds of dissolution media reveal certain advantages compared with phloretin and the physical mixture.The solubility in pH=1.2 hydrochloric acid buffer solution was increased approximately by 1.60 folds compared to raw material.Furthermore,the cocrystal products remain stable under high temperatures and high humidity conditions. Conclusion Phloretin-4,4'-bipyridine cocrystal with good stability can significantly improve the solubility of phloretin.
As a new method of drug combination therapy,drug-drug cocrystals can optimize the physicochemical properties of drugs,give play to the synergistic and dual drug therapeutic effects,and overcome the defects in traditional combination drugs without changing the chemical structure of the active components of the drug.In recent years,drug-drug cocrystal has been a hot research topic in solid chemical drug.This paper reviewed the design and prediction methods of drug-drug cocrystal,and the preparation methods and application advantages,to provide some reference for the subsequent application in drug research and development.
Since the first pharmaceutical cocrystal was reported in 1961,it has continuously gained interest from the industry due to its ability to improve the physicochemical properties,especially the thermodynamic solubility,flowability,hygroscopicity and taste of the active pharmaceutical ingredients.Additionally,recent works illustrated that forming cocrystals could improve the therapeutic effects and reduce the side effects,being closely watched in the modern pharmaceutic field.Some cocrystal-loaded drugs have already been marketed,and there are more cocrystals are being investigated or entering clinical trials.Hot melt extrusion is an advanced technologies that allow molecular-level mixing via applying heat,pressure,and mechanical force during the extrusion process.It is an environmentally friendly process because of free of using organic solvents.It is also an identical continuous process that offers higher productivity,better quality,and lower costs.The current review discussed the advantages of cocrystals from both pharmaceutical and physicochemical perspectives,as well as introduced the novel co-crystallization approaches utilizing continuous hot melt extrusion technologies.Furthermore,we analyzed in detail the current advantages and disadvantages of using such technologies and the challenges and opportunities we were facing.
Since the U.S.FDA approved the first deuterated drug,deuterated drugs have gradually become a research hotspot,because they can reduce metabolic efficiency,effectively prolong drug half-life,reduce the frequency of drug use and improve compliance.And they have the advantages of short research time,low cost and patent recognition.The problem that has long restricted the development of deuterated drugs is the detection method.Therefore,this paper summarized the detection methods and prospected the future development of the deuterated drug.
Pharmaceutical cocrystal,as one of the research directions of polymorphic drugs,has become a new hotspot in pharmaceutical research because of their characteristics of improving the physical and chemical properties without involving the chemical structure change of bulk drugs,thus improving the pharmaceutical properties of compounds.This article analyzed and summarized the general situation of patent applications and patent technology content from different perspectives by making statistics of domestic pharmaceutical cocrystal patent applications in last 20 years,and understands the development,current situation and current competition pattern of pharmaceutical cocrystal in China.The active pharmaceutical ingredient(API), cocrystal former(CCF)and patent protection objects in the patents were summarized.Solutions for patent invalidity were discussed to provide reference for the patent strategy planning and industrial policy formulation of pharmaceutical cocrystal development in China.It might also help Chinese research institutions and enterprises to save time and funds in the research and development of pharmaceutical cocrystal,and improve the starting point of research and development.
Objective To summarize the packaging standard system and its development in European Pharmacopoeia, and to provide reference for the establishment and optimization of the pharmaceutical packaging standard system in China. Methods The structure of the packaging standard system and the contents of the standards in European Pharmacopoeia were analyzed, the relationship between the standards was compared,and the applicability of the relevant strategy was evaluated. Results The packaging standard system in European Pharmacopoeia has remained relatively stable and been continuously improved in line with the needs of development.The standards of materials were of distinctive characteristics, and the suitability and operability of the standards are reasonably balanced. Conclusion The expectation management of packaging standards and the management policy of materials and accepted additives in European Pharmacopoeia are of great reference value to the construction of the pharmaceutical packaging standard system in our country.
Objective To study on the pharmaceutical packaging standard system and the latest progress in the United States Pharmacopoeia (USP),and to provide reference for the establishment and optimization of the pharmaceutical packaging standard system in China. Methods The structure of the pharmaceutical packaging standard system in USP and their contents were analyzed,the relationship among the packaging products standards,method standards,guidance for pharmaceutical packaging in USP were compared and analyzed. Results The pharmaceutical packaging standard system in USP is relatively complete,and the evaluation standards for pharmaceutical packaging materials have distinctive characteristics.The applicability of the standards is more comprehensively throughout the entire life cycle of pharmaceutical packaging material and pharmacopoeia forum updates periodically. Conclusion The relatively complete standards for pharmaceutical packaging materials in USP,mutually-supporting product standards plus evaluation standards throughout the entire life cycle of pharmaceutical packaging material are of great reference value to the construction of Chinese pharmaceutical packaging standard system.
Objective To provide a reference for the construction of pharmaceutical packaging materials standards in the 2025 edition of the Chinese Pharmacopoeia by analyzing the relevant content of pharmaceutical packaging materials in the 18th edition of the Japanese Pharmacopoeia. Methods The standards for pharmaceutical packaging materials in the Japanese Pharmacopoeia were summarized and sorted.The form of the standard,the variety and items of packaging materials control,and the focus of quality control were introduced. Results The Japanese Pharmacopoeia adopts a general rule form,focusing on the quality control of glass,plastic,and rubber closure for injections by combining test methods and requirements.The standard also focuses on the evaluation of the packaging suitability, full life cycle management,establishment of control items based on the characteristics of the preparations,packaging integrity evaluation of sterile materials, and coordination with international standards. Conclusion The standard for packaging of preparations is an important basis for quality control of pharmaceutical packaging materials. Learning from the standard form and quality control focus in the Japanese Pharmacopoeia can help to improve and enhance the standards of pharmaceutical packaging materials in China to meet the needs of scientific regulation and industry development.
Objective To introduce the standard system and content of International Organization for Standardization (ISO) for pharmaceutical packaging materials, to provide reference for building China's standard system for pharmaceutical packaging materials,and to promote the development of China's pharmaceutical packaging industry. Methods The latest data and standards related to pharmaceutical packaging materials formulated by ISO/TC76 were collected and sorted.The structure and main content of ISO/TC76's standard system for pharmaceutical packaging materials were analyzed.And the latest progress in developing and revising standards was introduced. Results The ISO standard system for pharmaceutical packaging materials had a complete and clear structure,and the content of the standards was good both in scientific rigor and flexibility. Conclusion The ISO standard system is comprehensive,and most of the standards in ISO/TC76's standard system for pharmaceutical packaging materials are product standards.The Chinese Pharmacopoeia is an independent standard system structure.And its pharmaceutical packaging materials standards include not only conventional technical specifications,but also product testing methods, inspection rules,naming principles and other aspects.The ISO standard system for pharmaceutical packaging materials can provide some guidance for building China's standard system.We should pay attention to the scientificity and influence of ISO standards,while also dialectically understand ISO standards combining actual situations in China.
Objective To compare the differences in chemical constituents between a traditional decoction and dispensing granules of traditional Chinese medicine of Guizhi Gancao decoction. Methods Under real-world conditions,the above two kinds of decoction were collected and prepared,and the characteristic chromatograms of Guizhi Gancao decoction were established by HPLC method.The types of chemical components,the content of index components (liquiritin,ammonium glycyrrhizinate,cinnamic acid,cinnamaldehyde),the area of common peaks,and the similarity of characteristic chromatograms were used as evaluation indexes. Results The amounts of chromatographic peaks were 25 (traditional decoction),23 (granule of factory A),22 (granule of factory B),and 20 (granule of factory C),respectively.The content of the index components of each manufacturer in the granules was different (P<0.05).The contents of liquiritin were in the following order: factory A > factory B (P<0.01)≈traditional decoction(P>0.05)> factory C (P< 0.05).The order of cinnamic acid content was factory B > traditional decoction (P<0.01)≈factory A(P>0.05)> factory C (P< 0.05).The order of ammonium glycyrrhizinate content was factory A > factory B (P<0.01) ≈traditional decoction(P>0.05)> factory C (P<0.01).The content of cinnamaldehyde was almost undetectable in all 3 granules.The sum of the common peak area of the 3 granules were lower than that of the traditional decoction.The sum of the common peak area of the traditional decoction was normalized to 1,and the other (A,B,C 3 manufacturers) were equivalent to 0.64,0.47,0.14,respectively.The similarity between 3 granules was high (above 0.8),and the similarity between granules and traditional decoction was lower (below 0.4). Conclusions Under this experiment condition,there are differences in the chemical composition of traditional decoction and dispensing granules,especially the volatile components.There are also differences in the quality of granules of different manufacturers,indicating that a unified quality standard in formula granules of Guizhi Gancao decoction is needed.
The release of the Announcement on Ending the Pilot Work of Traditional Chinese Medicine Formula Granules in 2021 marked the end of the pilot work of Chinese medicine formula granules in 1993. With the successful introduction of national and provincial standards related to traditional Chinese medicine formula granules,the quality standard of formula granules gradually increased.The formula granule industry has also entered a new stage of development with the advent of the "post-pilot era".However,the research on the difference between a traditional decoction and the standardization of clinical application may not be solved by implementing these policies,so systematic and in-depth research is still needed.In this paper,the related articles on the comparative research between the formula granule decoction and the traditional decoction were reviewed,the problems existed in the theoretical design ideas and the unreasonable application of the experimental methods in the existing comparative research were summarized,and methods and suggestions were proposed based on the actual situation,in order to provide more open ideas and more technical choices for the future comparative research,and provide a specific reference for the rational application of formula granules in clinical and industry standard development.
The consistency evaluation of traditional Chinese medicine dispensing granules (TCM dispensing granules) and traditional Chinese medicine decoction (TCM decoction) is the key to solving the problem of whether they are equivalent.In recent years,many researchers have compared the consistency of TCM dispensing granules and TCM decoction in terms of chemical components and ingredients absorbed into the blood.However,due to the lack of a suitable evaluation process and clear evaluation standards,their consistent evaluation has a series of problems,such as the lack of systematic index selection and evaluation level,unreasonable data processing methods,and so on.Therefore,taking the consistency evaluation process of TCM dispensing granules and TCM decoction as the context,this article makes a review of the problems that arise in the consistency evaluation process of them,and provides suggestions from the selection of evaluation objects and evaluating methods and the establishment of evaluation standards.It is expected to provide a reference for the establishment of consistency evaluation system of traditional Chinese medicine formula granule decoction or other imitation traditional Chinese medicine dosage forms,to promote the rational application of traditional Chinese medicine formula granules and other relevant traditional Chinese medicine dosage forms.
As an important part of traditional Chinese medicine decoction pieces,multi-source traditional Chinese medicine decoction pieces account for about 24% of the total number of medicinal materials and decoction pieces in the 2020 edition of Chinese Pharmacopoeia.However,there are some problems in multi-source traditional Chinese medicine decoction pieces,such as easy confusion and difficult identification,which need to be solved by scientific and efficient identification methods.Therefore,we analyzed the varieties of multi-source traditional Chinese medicine and the methods for identifying multi-source traditional Chinese medicine decoction pieces in the current Chinese Pharmacopoeia and combed the literature on the identification of multi-source traditional Chinese medicine decoction pieces in this study.To comprehensively reflect the research progress of the identification methods of multi-source traditional Chinese medicine decoction pieces,provide a reference for the accurate identification of the source of traditional Chinese medicine decoction pieces,and also provide a particular reference for the adulteration identification of traditional Chinese medicine decoction pieces.
Interventional therapy is the first choice for treating advanced hepatocellular carcinoma (HCC).The embolization effect of embolic material directly determines the therapeutic effect.In recent years,multifunctional embolic microspheres based on electrospray technology have been developed with the development of interdisciplinary subjects including materials science,medical imaging and biomedical engineering.By accurately controlling the size of microspheres and introducing the inherent visibility under medical imaging techniques,it provides a solid foundation for the precise interventional treatment of HCC.In addition,the preparation method is easy to introduce a variety of functional substances,which provides convenience for the combination of interventional therapy and other therapeutic methods.This article reviewed the advantages of multifunctional embolic microspheres fabricated by electrospray technology and looked forward to the opportunities and challenges of functional embolic microspheres in interventional therapy of tumors.
The pathogenesis of depression is highly complicated and has not been fully elucidated.Numerous clinical and preclinical studies suggested that serotonergic (5-HT) neurological dysfunction critically contributed to depression.In addition to the serotonin transporter (SERT),multiple subtype receptors in the 5-HT nervous system are related to depression.Among them,5-HT1A and 5-HT2A receptors are most closely associated.Brain widely distributed 5-HT2A receptors provide a fundamental basis for regulating mood and perception.5-HT2A receptors modulate the level of monoamine transmitters in the brain by directly or indirectly regulating monoamine transmitters' release to participate in depression development.5-HT2A receptors antagonists enhanced the therapeutic effects of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) for treatment-resistant depression and reduced adverse reactions such as sexual dysfunction and sleep disorder.Several 5-HT2A receptor-targeted antidepressants were approved for clinical treatment,and many compounds are currently being researched in clinical or preclinical studies.This review briefly discussed the relationship between 5-HT2A receptors and depression and summarized the research progress of antidepressants targeting 5-HT2A receptors to provide information for antidepressant research.
Objective To establish a method for tracing the origins of Lonicera japonica. Methods Fourier transform infrared (FTIR) and ultra-high performance liquid chromatography (UPLC) were used to establish fingerprints of L.japonica of different varieties in Shandong and Yunnan Province.The samples' geographical origin was investigated using FTIR and UPLC combined with pattern recognition analysis,including similarity analysis,principal component analysis (PCA),and hierarchical cluster analysis (HCA). Results The similarities of UPLC fingerprints were greater than 0.9,which suggested that the quality of these samples was uniform.Moreover,the UPLC fingerprint can discriminate the origins of different individuals from various sources.But it cannot distinguish the other L.japonic varieties from the same place.Furthermore,FTIR was applied to trace the origins and varieties of L.japonica,and satisfactory results were achieved. Conclusion The method based on FTIR,UPLC fingerprints,and chemometrics in this paper can provide a technical basis for tracing the source of L.japonica from different places.
Objective To investigate the effects of different drying methods (drying,sun drying,vacuum drying and freeze drying) on the physical property and alkaloid dissolution of Corydalis rhizoma processed with vinegar,and to provide a theoretical basis for the selection of drying methods of Corydalis rhizoma processed with vinegar. Methods After preparing Corydalis rhizoma processed with vinegar, heat drying,sun drying,vacuum drying, and vacuum freeze drying were carried out respectively. The physical property parameters such as rehydration rate, drying rate and hardness were compared. At the same time, the dissolution of tetrahydroclofenac,protopine, tetrahydrocoptimetine, tetrandrine, tetrahydropalmatine,berberine hydrochloride, palmatinehydrochloride, dehydroviodecanine were measured by UPLC method. Multi-index combined with chemometrics to evaluate the effects of different drying methods on the quality and component dissolution of Corydalis rhizoma processed with vinegar. Results After drying,the surface of the medicinal materials shrinks,forming a relatively dense structure,and the ingredients dissolve slowly.After freeze-drying,the medicinal materials are loose and porous, light in texture and low in water content, and the ingredients dissolve quickly. Conclusion Considering multiple indicators such as physical parameters and internal components,the freeze-dried vinegar-processed Corydalis rhizoma is significantly different from other drying methods.In the first 20 minutes, the dissolution rate of the components after the freeze-drying method was significantly higher than that of the other three methods. According to the actual clinical decoction,freeze-drying method should be used.
Objective To compare the cost-effectiveness of different anticoagulants for the treatment of portal vein thrombosis (PVT) in cirrhosis,and to provide a reference for clinical selection of economic anticoagulants for these patients. Methods A decision tree model was constructed to compare the economics of different anticoagulants for the treatment of PVT in cirrhosis from the healthcare provider's perspective.The treatment success rate was used as the health outcome,and cost data were obtained from prices in a real medical setting of our hospital.A cost-effectiveness analysis was performed for each anticoagulation regimen,and sensitivity analysis was performed on the results to verify the robustness of the results. Results Compared to the non-anticoagulation group,the incremental cost-effectiveness ratio (ICER) of the warfarin regimen was 1 204.70 yuan,the ICER of the direct oral anticoagulants (DOACs) regimen was 2 600.73 yuan,and the ICER of the low molecular weight heparin (LMWH) regimen was 17 689.32 yuan.DOACs regimen was most cost-effective at a willingness-to-pay(WTP) threshold of 14 590.90 yuan.The results of the univariate sensitivity analysis showed that the daily cost of DOACs had the greatest impact on the outcome.Warfarin was more cost-effective than DOACs when the daily cost of DOACs was higher than 21.03 yuan.The cost-effectiveness acceptability curve indicated that WTP was 14 590.90 yuan,the probability of being cost-effective of DOACs was 53.7%. Conclusion DOACs regimen for PVT in cirrhosis is cost-effective compared to warfarin and LMWH regimens,which needs to be confirmed by more clinical studies.
Objective To evaluate therapeutic drug monitoring and efficacy of meropenem in patients with continuous renal replacement therapy(CRRT) and patients with renal insufficiency but without CRRT,and to evaluate the effect of CRRT on the clearance of meropenem. Methods Patients with renal insufficiency receiving meropenem treatment and therapeutic drug monitoring in the Affiliated Suzhou Hospital of Nanjing Medical University from January 2019 to June 2021 were collected retrospectively.They were divided into the CRRT group and the non-CRRT group.Dosage regimen,blood trough concentration,and clinical efficacy were compared between the two groups. Results A total of 74 patients were included and divided into the CRRT group(21 cases)and the non-CRRT group(53 cases).The blood trough concentration of CRRT group was higher than that of non-CRRT group(P<0.01).The blood trough concentration of the CRRT group in dose of 1 g,q8h was higher than that of the non-CRRT group(P<0.05).The rate of clinical efficacy in the non-CRRT group was higher than that in the CRRT group(P<0.05).The clearance rate of gram-negative bacteria in the group with blood trough concentration>4MIC was higher than that of another group with blood trough concentration<4MIC(P<0.01).The linear regression analysis results indicated a certain correlation between blood trough concentration and ultrafiltration rate(r=-0.454,P<0.05). Conclusion Patients with CRRT had higher blood trough concentration and less clearance of meropenem than patients with renal insufficiency but without CRRT.There was a certain correlation between blood trough concentration and ultrafiltration rate in CRRT patients.For patients with Multi-resistant pathogens,keep blood through concentration>4MIC can obtain better clearance of gram-negative bacteria.
This article mainly examines the precautions in prescription check,blending,reexamination,and drug distribution of Chinese herbal pieces.The six categories include the following: decocted and ingested Chinese herbal pieces,Chinese herbal pieces with toxic ingredients,anesthesia herbal pieces,herbal pieces contraindicated during pregnancy,herbal pieces with liver and kidney toxicants,and prescription-based herbal pieces.The article also underscores vital technical points while preparing specific Chinese herbal pieces.These necessary measures also offer a reference for traditional Chinese medicine dispensing personnel in pharmaceutical care.