Arsenic trioxide albumin microspheres (As2O3-BSA-NS) were prepared by using methods of chemical cross-linking. The desirability function (DF), calculated according to the size (<1 microm) distribution, drug loading and drug trapping efficiency, was introduced as a total index for the microspheres formulation. Four factors, inculding W/O ratio, decentralization speed, BSA concentration and stirring stabilization time, were selected and arranged in an orthogonal experimental table. The release characteristic was studied by the drug release experiment in vitro. The four factors affected DF differently. Decentralization speed behaved as the maximum (P<0.01), followed by BSA concentration (P<0.05) and the W/O ratio dose (P<0.05). Stirring stabilization time did not influence DF (P>0.05). The release experiment in vitro showed that As2O3 in As2O3-BSA-NS was released more slower than pure As2O3. It was concluded that regular As2O3-BSA-NS may be prepared by the methods of chemical cross-linking, which was optimized by orthogonal experimental analysis of different factors, and the microspheres can release As2O3 slowly.
Arsenicals/*chemistry ; Cross-Linking Reagents/pharmacology ; Delayed-Action Preparations ; Drug Carriers/*chemistry ; Drug Delivery Systems ; Microspheres ; Oxides/*chemistry ; Serum Albumin, Bovine/*chemistry ; Technology, Pharmaceutical

Some of traditional Chinese medicine (TCM) contain arsenide, such as realgar. The total amount of arsenic in the TCM exceeds the limits according to related regulations. But the roles of arsenic in TCM or its side-effects depend on its species existed in those therapies, not the total amount of arsenic. Therefore, in recent years, the analysis of arsenic in TCM focuses on the species of arsenic. The present paper summarized some methods and techniques in the speciation analysis of arsenic in TCM, in order that optimal methods can be chosen and the roles of arsenic could be evaluated properly.
Arsenicals ; analysis ; Chromatography ; methods ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; Electrophoresis, Capillary ; methods ; Materia Medica ; chemistry ; Plants, Medicinal ; chemistry ; Spectrophotometry, Atomic ; methods

OBJECTIVETo explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic.

METHODThe realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing.

RESULTAsenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain.

CONCLUSIONAsenic can be absorbed and extensively distributed in various organs or tissesses after realgar administration in rats. Long-term use of realgar caused high asenic accumulation in various tissueses, including blood, kidney, liver, and brain. The nephrotoxicity and hepatotoxicity of realgar could be associated with the asenic accumulation in relative organs. Blood is the target of the most highest distribution and accamulation of asenic after realgar treatment, that could be associated with the efficacy of realgar on the treatment of leakemia.

Animals ; Arsenic ; analysis ; chemistry ; pharmacokinetics ; toxicity ; Arsenicals ; administration & dosage ; adverse effects ; chemistry ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Solubility ; Sulfides ; administration & dosage ; adverse effects ; chemistry ; Time Factors

Sepiae Endoconcha is a common marine animal medicine,which generally contains high concentration of arsenic( As).The Chinese Pharmacopoeia( 2010 edition,part I) stipulated that the total As content of Sepiae Endoconcha should not exceed 2 mg·kg~(-1),while this limit was revised to 10 mg·kg~(-1) in the 2015 edition. So far,there is no research on the speciation of As in Sepiae Endoconcha,which made it hard to accurately evaluate its security risk. In this study,32 batches of Sepiae Endoconcha from different sources were collected. The safety risk assessment was carried out by determining the total As content and As speciation,inorganic As[As( Ⅲ),As( Ⅴ) ]and organic As( MMA,DMA,As C,As B) by HPLC-ICP-MS,and then the limit standard was discussed. The results showed that As B was the main form of As in Sepiae Endoconcha,followed by DMA and As( Ⅴ) ． Of the 32 batches of Sepiae Endoconcha,9 batches( accounting for 28%) were detected possessing i As. The maximum concentration of As( Ⅲ) was 103. 3 μg·kg~(-1),and the maximum concentration of As( Ⅴ) was 222. 4 μg·kg~(-1). According to the limit of i As in food,18. 75% of the samples exceeded the standard. The results indicate that there is no simple positive correlation between total As and As morphology in Sepiae Endoconcha. Besides,there is a risk in the total As limit,especially after the relaxation of the total As limit. The problem of high i As content caused by pollution and other factors is difficult to regulate. Since the toxicity of inorganic As is much higher than that of organic As,it is of great practical significance to establish inorganic As form limits in Sepiae Endoconcha.
Animals ; Arsenic/analysis* ; Arsenicals/analysis* ; Chromatography, High Pressure Liquid ; Drug Contamination ; Environmental Pollution ; Mass Spectrometry ; Medicine, Chinese Traditional ; Sepia/chemistry*

OBJECTIVETo optimize the different components proportions of the Realgar floating tablets for gastric retention by uniform design and correlation analysis.

METHODWith the different dosage of hydroxypropyl methyl cellulose (HPMC) as the tablets frame matrix, uniform design and correlation analysis were used to optimize the best component proportions of formula, and to measure the dissolution of the tablets in vitro.

RESULTDissolution of the tablets in vitro was conformed to the expectation of experiment. The drug-release mechanism was by diffusion and corrosion at the same time.

CONCLUSIONThe Realgar floating tablets for gastric retention achieved the goal of design, which demand sustained release and safety.

Administration, Oral ; Arsenicals ; administration & dosage ; chemistry ; pharmacokinetics ; Delayed-Action Preparations ; Hypromellose Derivatives ; Materia Medica ; administration & dosage ; chemistry ; pharmacokinetics ; Methylcellulose ; analogs & derivatives ; chemistry ; Povidone ; chemistry ; Solubility ; Stomach ; metabolism ; Sulfides ; administration & dosage ; chemistry ; pharmacokinetics ; Tablets ; Technology, Pharmaceutical ; methods

Realgar-containing Niuhuang Jiedu tablet (NHJD) has been applied in clinic for more than 800 years. However, because realgar contains arsenic (As), it has aroused wide concerns and controversies both at home and abroad. Currently, there are two misunderstandings about realgar-containing Chinese patent medicines. First, some people exaggerated realgar's toxicity as that of arsenic. Second, they recommended to remove realgar from traditional Chinese medicine compounds. In this paper, the authors summarized the advance in studies on NHJD, and proposed different opinions: (1) It is inappropriate to take total As as the index in safety evaluation of NHJD. (2) The toxicity of NHJD is dependent on the dose and duration of administration. (3) Realgar is an active ingredient of NHJD, and shall be deeply studied. Classic realgar-containing traditional Chinese medicine prescriptions, such as Niuhuang Jiedu tablet, shall be evaluated with rigorous modern scientific basis, with the aim to guide rational and safe application.
Animals ; Arsenicals ; adverse effects ; chemistry ; therapeutic use ; Chemistry, Pharmaceutical ; methods ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; adverse effects ; methods ; Sulfides ; adverse effects ; chemistry ; therapeutic use ; Tablets ; Time Factors ; Treatment Outcome

This study was aimed to investigate the modulating effects on telomere length and telomerase activity in K562 cells treated by arsenic trioxide, ginseng saponin, beta-elemene alone or in combination with cyclophosphamide (CTX) and to explore the possible mechanism and new therapy for acute leukemia. Human erythroleukemic cell line K562 was co-cultured with the above-mentioned drugs. Cells were collected after 24, 48 and 72 hours for further detection. Telomere length and telomerase activity were detected by Southern-blot and PCR-ELISA respectively. The effects of these drugs were observed at different concentrations and exposure time. The results showed that (1) ginseng saponin, arsenic trioxide, beta-elemene, or CTX could completely inhibit the telomerase activity of K562 cells at proper concentrations and exposure time. The inhibiting effects were enhanced when the three former drugs were used with CTX. Telomerase activity decreased proportionally with the concentrations and length of time. (2) viability of K562 cells was decreased after being co-cultured with arsenic trioxide, ginseng saponin, beta-elemene and CTX. The level of inhibition depends on the concentration and exposure time. (3) telomere length of K562 cells was 5.36 +/- 0.18 kb. After being co-cultured with those drugs for 72 hours, telomere length was 5.90 kb -6.50 kb, significantly longer than that of control (5.18 - 5.35 kb). It is concluded that arsenic trioxide, ginseng saponin, and beta-elemene can inhibit the growth and telomerase activity of K562 cells. The inhibiting effects were enhanced when they were used in combination with CTX. The depression of telomerase activity may be one of the mechanisms of anti-tumor effect. Less dosage and shorter course can be expected when arsenic trioxide, ginseng saponin, and beta-elemene are used in combination with CTX. When telomerase activity was depressed, the telomere length prolonged a little, indicating K562 cell line may extend telomeres by some alternative way other than telomerase activation.
Arsenicals ; pharmacology ; Cyclophosphamide ; pharmacology ; Drug Synergism ; Humans ; K562 Cells ; Oxides ; pharmacology ; Panax ; chemistry ; Saponins ; pharmacology ; Sesquiterpenes ; pharmacology ; Telomerase ; drug effects ; metabolism ; Telomere ; drug effects

OBJECTIVEModeling HAdV-3 infect Hep-2 cells in vitro. The effect of realgar nanoparticles on the expression of HAdV-3 is detected by using fluorescent quantitative PCR.

METHODSThe experiment is divided into four groups: Hep-2 cells control group, HAdV-3 virus control group, realgar nanoparticle group and ribavirin group. In order to detect HAdV-3 viral load, add realgar nanoparticles and ribavirin in vitro and remain that vitro for 24 hours when HAdV-3 has infected Hep-2 cells, extract total DNA of Hep-2 cells infected by HAdV-3, and establish Real-time PCR reaction system of every experimental groups.

RESULTThe Hep-2 cells group has no amplification curve, the Ct value is greater than 35, which illustrate HAdV-3 pathogen detection is negative. However, realgar nanoparticles group, ribavirin group and the HAdV-3 group have amplification curve, the Ct values are 29.30 +/- 0.08, 33.05 +/- 1.29, 26.01 +/- 0.25 respectively, which illustrate HAdV-3 pathogen detection is positive. The viral copy amount of the adenovirus group(66 699 932 +/- 23.85) is more than that of realgar nanoparticles group (912 435.44 +/- 16.57), and much greater than that of ribavirin group (459 124.84 +/- 12.82) (P < 0.05).

CONCLUSIONThe model of Hep-2 cell infected by HAdV-3 is reliable. The method of quantitative PCR is sensitive and specific. Realgar nanoparticles have a certain inhibition role for adenovirus nucleic acid replication.

Adenoviridae Infections ; virology ; Adenoviruses, Human ; drug effects ; genetics ; physiology ; Arsenicals ; chemistry ; pharmacology ; Gene Expression Regulation, Viral ; drug effects ; Hep G2 Cells ; Humans ; Nanoparticles ; chemistry ; Sulfides ; chemistry ; pharmacology ; Virus Replication ; drug effects

Disinfection means killing or removing pathogenic microorganisms in media to realize a harmless process. A disinfectant, which is also referred to as a disinfection medicine in relevant regulations, is the medicine used to kill microorganisms for the purpose of disinfection. The disinfectants prepared from plants (including traditional Chinese herbal medicines) and the extracts thereof are called herbal disinfectants. China has a long history of using herbal disinfectants. As early as in 533 A.D., the use of Cornel to sterilize well water was recorded in Necessary Techniques for Qi People by Jia Enxie of the Beiwei Dynasty. During the Dragon Boat Festival, people often use fumigants made of traditional Chinese herbal medicines like Chinese Atractylodes, Argy Wormwood Leaf and Red Arsenic Sulfide to smoke their houses, so as to ward off plagues and drive away evils. In fact this is now a kind of disinfection practice.
Arsenicals ; pharmacology ; Atractylodes ; chemistry ; China ; Disinfectants ; pharmacology ; Fumigation ; Medicine, Chinese Traditional ; Mucous Membrane ; microbiology ; Plant Extracts ; chemistry ; pharmacology ; Plant Leaves ; chemistry ; Skin Diseases, Infectious ; microbiology ; prevention & control ; Sulfides ; pharmacology

OBJECTIVE: To investigate the effect of nano-realgar on proliferation and apoptosis of cervical cancer cells.
 METHODS: Different cervical cancer cell lines (Caski/HPV16+, adeno carcinoma; Hela/HPV18+, squmous carcinoma; C33A/HPV-, adeno carcinoma) were incubated with nano-realgar at different concentrations (5, 10, 20, 40 mg/L) for different times (24, 48, 72, 96 h). The morphology was observed under phase contrast microscope. The cell viability and apoptosis were examined by MTT and flow cytometry, respectively.
 RESULTS: The inhibitory effect of nano-realgar on the proliferation of cervical cancer cells was in a dose-dependent manner, with a range of inhibitory rate from 9.02% to 49.06%. Taking the group (20 mg/L) for an example, the inhibitory rates for Caski, Hela and C33A were 39.15%, 36.17% and 30.56%, respectively. The results of flow cytometry showed that the nano-realgar induced apoptosis in a concentration-dependent manner, with a range of apoptosis rate from 19.29% to 99.54%. Also taking the group (20 mg/L) for an example, the apoptosis rates for Caski, Hela and C33A were (60.43 ± 2.88)%, (41.95 ± 3.01)% and (43.49 ± 2.19)%, respectively. High concentration of nano-realgar (20 or 40 mg/L) could induce block of Hela and Caski at G2/M stage.
 CONCLUSION Nano-realgar can inhibit the proliferation of different cervical carcinoma cell lines and can induce the cell apoptosis. The inhibitory effect on cell proliferation is strongest for Caski, followed by Hela and C33A. It can also induce G2/M stage block on HPV positive cervical cancer cells at high enough concentration.
Adenocarcinoma ; pathology ; Apoptosis ; drug effects ; Arsenicals ; chemistry ; Carcinoma, Squamous Cell ; pathology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Female ; HeLa Cells ; drug effects ; Humans ; Nanoparticles ; chemistry ; Sulfides ; chemistry ; Uterine Cervical Neoplasms ; pathology