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1.
Zhonghua Gan Zang Bing Za Zhi ; 30(6): 612-617, 2022 Jun 20.
Artículo en Zh | MEDLINE | ID: mdl-36038322

RESUMEN

Objective: To compare and analyze the clinical curative effect and safety of chemoembolization with drug-loaded microspheres of different particle sizes (D-TACE) for the treatment of hepatocellular carcinoma. Methods: Clinical data of 281 cases with hepatocellular carcinoma treated with drug-loaded microspheres-transarterial chemoembolization (TACE) were retrospectively analyzed. According to the different particle sizes of drug-loaded microspheres, they were divided into 100~300 µm (small particle size) and 300~500 µm (large particle size) group. Tumor response rate and complication conditions at 1, 3, and 6 months after chemoembolization were compared. The overall survival time of the two groups were analyzed. Quantitative data conformed to normal distribution and homogeneity of variance were compared using t-test, while other with Wilcoxon signed rank-sum test. Qualitative data were compared using χ2 test. Kaplan-Meier method was used for survival analysis, and the differences in survival were analyzed using Log-rank test. P<0.05 was considered as statistically significant. Survival curves and histograms were drawn using GraphPad Prism9.1 software. Results: The complete remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 31.25%, 30.15%, and 42.45% and 18.25%, 15.79% and 24.74%, respectively, and the differences were statistically significant between groups (P1 month=0.012, P3 month=0.009, P6 month=0.008, P<0.05). The objective remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 88.19%, 76.99%, and 70.75% and 81.02%, 72.81% and 53.60%, respectively. Six months after surgery, the small particle size group (objective response rate = 70.75%) was significantly higher than the large particle size group (objective response rate=53.6%, P=0.012). The disease control rates of the small particle size group were 95.14%, 83.33%, and 74.53%, while large particle size group were 91.24%, 81.58%, and 64.95%, respectively, with no statistically significant difference between the two groups. However, the incidence of postoperative biliary tumors (6.20%) was significantly higher in the small-size than large-size group (0.70%), and the difference was statistically significant (P<0.05, P=0.03). There were no statistically significant differences between other adverse events such as post-embolization syndrome, liver abscess, and myelosuppression. The median survival time of the small and large particle size groups was 31.8 months and 20.5 months, respectively, but the difference was not statistically significant (P=0.182). Conclusions: In the treatment of hepatocellular carcinoma with D-TACE, the short-term curative effect of the small particle size group was better than large particle size group, but the incidence of biliary tumors was high, and D-TACE of different particle sizes had no significant effect on long-term survival.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/métodos , Humanos , Neoplasias Hepáticas/patología , Microesferas , Tamaño de la Partícula , Estudios Retrospectivos , Resultado del Tratamiento
2.
Zhonghua Fu Chan Ke Za Zhi ; 56(10): 705-711, 2021 Oct 25.
Artículo en Zh | MEDLINE | ID: mdl-34823320

RESUMEN

Objective: To investigate the effect and mechanism of tumor necrosis factor α (TNF-α) and its inhibitor etanercept (ETA) on the invasion ability of extravillous trophoblast in patients with unexplained recurrent spontaneous abortion (URSA). Methods: (1) Patients were collected from March to June in 2019. They were divided into the URSA group (n=15) and the normal control group (n=15), according to whether diagnosed with URSA or not. The mRNA expression levels of TNF-α in villi tissue of patients in the two groups were detected by quantitative real-time PCR (qRT-PCR). (2) The mRNA and protein expression levels of matrix metalloproteinase-2 (MMP-2), Slug and CXC chemokine rceptor 4 (CXCR4) in HTR-8/SVneo cells were detected by qRT-PCR or western blot after being stimulated by exogenous TNF-α (0.2, 2, 20 ng/ml) alone or TNF-α along with ETA, or phosphate buffered saline (PBS) as control. (3) The invasion ability of HTR-8/SVneo cells was investigated by transwell test after stimulating by TNF-α alone or TNF-α along with ETA. (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells, which were stimulated by TNF-α (2 ng/ml) alone after nuclear factor-κB (NF-κB) inhibitor, BAY 11-7028, preconditioning, were detected by qRT-PCR or western blot. Results: (1) The mRNA expression level of TNF-α in villi tissue of URSA group (4.10±0.49) was 4.1 times as much as the normal control group (t=10.51, P<0.05). (2) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells of TNF-α group were significantly lower than those in PBS control group (P<0.05) and those in TNF-α along with ETA group (P<0.05). (3) The invasion ability of HTR-8/SVneo cells in TNF-α group was significantly decreased than PBS group and TNF-α along with ETA group (78±14 vs 373±26 vs 227±44, P<0.05). (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells with BAY 11-7028 preconditioning (mRNA: 1.03±0.10, 1.03±0.06, 1.09±0.08; protein: 1.09±0.03, 1.49±0.03, 1.12±0.03) were significantly higher than without preconditioning after being stimulated by TNF-α (all P<0.05). Conclusions: The expression of TNF-α in the villi of URSA patients is much higher than normal early pregnant women. TNF-α could decrease the capacity of invasion by suppressing the expression of MMP-2, Slug and CXCR4 through NF-κB signaling pathway in extravillous trophoblast cells. While ETA could improve the invasiveness capability of extravillous trophoblast cells through inhibiting the negative effect of TNF-α.


Asunto(s)
Aborto Habitual , Etanercept , Factor de Necrosis Tumoral alfa , Línea Celular , Movimiento Celular , Etanercept/farmacología , Femenino , Humanos , Metaloproteinasa 2 de la Matriz/genética , Embarazo , Receptores CXCR4 , Factores de Transcripción de la Familia Snail , Trofoblastos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología
3.
Zhonghua Fu Chan Ke Za Zhi ; 54(5): 324-329, 2019 May 25.
Artículo en Zh | MEDLINE | ID: mdl-31154714

RESUMEN

Objective: To compare the expression of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in tissue and fluid samples from patients with endometriosis, and investigate whether LIF and IL-6 regulate VEGF in human endometriotic stromal cells (ESC). Methods: The levels of VEGF, LIF, IL-6 in serum, peritoneal fluid of patients with and without endometriosis were measured by ELISA. The mRNA of these three factors in the ectopic and eutopic endometrial tissue and stromal cells were measured by real-time PCR. ESC derived from ovarian endometriomas were cultured using the method of primary cell culture with LIF and IL-6, and the level of VEGF mRNA and protein were measured by the method of real-time PCR and ELISA respectively. Results: VEGF and IL-6 concentration were 1.2 and 1.3 times higher in the serum of patients with endometriosis than in the control group [(94±19) versus (78±17) ng/L; (45±14) versus (35±9) ng/L; all P<0.05]. VEGF and IL-6 concentration were 1.2 and 1.4 times higher in the peritoneal fluid of patients with endometriosis than in the control group [(110±25) versus (91±21) ng/L; (69±20) versus (49±15) ng/L; all P<0.05]. VEGF and IL-6 concentrations in peritoneal fluid of patients with endometriosis were 1.2 and 1.5 times higher than in serum (all P<0.01). VEGF, LIF and IL-6 mRNA expression were 2.2, 8.6, 44.7 times higher in ESC compared with the matching eutopic endometrial stromal cells (all P<0.01). LIF and IL-6 mRNA were 2.0 and 64.8 times higher in ectopic endometrial tissue than the matching eutopic endometrial tissue (all P<0.05).ESC cultured with LIF, IL-6 and LIF+IL-6 induce VEGF protein secretion [(106±18), (124±30), (140±27) ng/L] by 1.3, 1.5 and 1.7 times (all P<0.05). Conclusion: Overexpression of LIF and IL-6 may synergistically contribute to upregulation of VEGF in ESC and promote development of endometriosis.


Asunto(s)
Endometriosis/metabolismo , Interleucina-6/análisis , Factor Inhibidor de Leucemia , Células del Estroma/metabolismo , Regulación hacia Arriba/fisiología , Factor A de Crecimiento Endotelial Vascular , Células Cultivadas , Endometriosis/patología , Endometrio , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Células del Estroma/patología , Factores de Crecimiento Endotelial Vascular
4.
BMC Cancer ; 18(1): 281, 2018 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-29530011

RESUMEN

BACKGROUND: The primary pulmonary lymphoma (PPL), with a low incidence, was highly misdiagnosed in clinic. The present study analyzes the clinical features, laboratory and imaging data, pathologic characteristics, and summarizes misdiagnosis reasons of PPL cases, aims to provide a better understanding and increase the accuracy of early diagnosis and minimize the misdiagnosis of PPL. METHODS: The clinical data of 19 cases were collected from the first affiliated hospital of Wenzhou medical university (PRC) from April 2010 to May 2016. All cases were confirmed by pathology. The process of misdiagnosis was described. This study retrospectively analyzed the incidence, clinical presentation, laboratory examination, Chest CT scan and diagnosis of the cases. RESULTS: The symptoms of the 19 cases were dyspnea, fever, hemoptysis, chest pain or physical findings without obvious symptoms. Five patients were pneumonia-like, nine patients had lung single nodule or mass and four patients got pleural effusion, which were reported by computed tomography (HRCT) scan. There were 2 cases of Hodgkin lymphoma (HL), and 17 cases of non-Hodgkin lymphoma (NHL). In NHL cases, 12 cases were confirmed mucosa associated lymphoid tissue B lymphoma type, 3 cases were confirmed diffuse large B-cell lymphoma, angioimmunoblastic T-cell lymphoma and ALK positive anaplastic large cell lymphoma were one case separately. Clinical and imaging manifestation of PPL is untypical, but there are still some hints: 1) Fuzzy shadow at the edge of lung mass with air bronchogram; 2) Lung mass shadow stable for a long time; 3) Pneumonia-like changing without infections clinical and lab manifestation. Thirteen patients (68.4%) were misdiagnosed as pneumonia, lung cancer and tuberculosis initially. The term between initial diagnosis and final diagnosis lasted for half a month up to 2 years, with median time of 6 months. Two cases were misdiagnosed as tuberculosis. One case was misdiagnosed as small cell lung cancer. CONCLUSION: Clinical and imaging manifestation of PPL is untypical. Biopsies should be taken actively if the imaging findings don't match the symptoms or the anti-infection treatments to "lung infection" don't work. Accurate diagnosis requires adequate tissue sampling with appropriate ancillary pathologic studies. If clinical manifestation and the diagnosis don't match, repeated biopsy should be ordered.


Asunto(s)
Errores Diagnósticos , Enfermedad de Hodgkin/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfoma no Hodgkin/diagnóstico , Adulto , Anciano , Biopsia , Femenino , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/patología , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/patología , Tórax/diagnóstico por imagen , Tórax/patología , Tomografía Computarizada por Rayos X
6.
Clin Exp Dermatol ; 40(4): 438-40, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25683325

RESUMEN

Erythema induced by ultraviolet (UV)B light is a common skin reaction. Currently, three techniques, the Chromameter(®) CR-400, the Mexameter(®) MX16 and full-field laser perfusion imaging (FLPI), are widely used for dermatological evaluation of UVB-induced erythema. However, there is little known about the comparative performance of these three techniques. This study was therefore designed to evaluate the effectiveness of the three techniques. Our findings showed that the performance of Chromameter and Mexameter for measurement of UVB-induced erythema was very similar, while FLPI indicated acute erythema at D1 with the greatest fold change. Further studies of UVB dose-dependence need to be carried out.


Asunto(s)
Colorimetría/instrumentación , Dermoscopía/instrumentación , Eritema/diagnóstico , Imagen de Perfusión/métodos , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Enfermedad Aguda , Adulto , Eritema/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto Joven
7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(12): 2021-2025, 2022 Dec 10.
Artículo en Zh | MEDLINE | ID: mdl-36572479

RESUMEN

Objective: To analyze the performance of emergency response to 2019 novel coronavirus (2019-nCoV) positive cases in an international test competition in an Winter Olympic Game venue and provide evidences for the COVID-19 prevention and control in similar competitions. Methods: A retrospective analysis on the epidemiological investigation and nucleic acid test results of the cases, the implementation of prevention and control measures, including the communication with sport teams and others, was conducted. Results: The positive cases of 2019-nCoV among entering people were detected before entry, at airport, hotel and venue. Two positive cases were reported before entry, 2 positive cases infected previously and 3 asymptomatic cases were reported after the entry. The venue public health team and local CDC conducted epidemiological investigation and contact assessment jointly in a timely and efficient manner. No local secondary transmission occurred, but the nucleic acid test results of positive persons fluctuated, posing serious challenges to the implementation of prevention and control measures. Conclusion: In large scale international competition, there is high risk of imported COVID-19. It is necessary to fully consider the fluctuation of nucleic acid test results, the criteria for determination and cancellation of positive results and give warm care to positive cases in the emergency response.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Estudios Retrospectivos , Estaciones del Año
8.
Hereditas ; 147(2): 62-9, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20536544

RESUMEN

The direct sequencing of the Kit cDNA obtained from mutant mice was used to reveal the molecular nature of the W(-3Bao) ENU-induced mutation. There was a T to A transversion at the 441st nucleotide in the W(-3Bao) open reading frame (ORF), which introduced a pre-mature termination codon at residue 147. The gross embryonic development, hematopoiesis and spermatogenesis were examined in the mutant mice. There was no visible difference among the W(-3Bao/+), W(-3Bao/3Bao) and wild type embryos before embryonic day 12.5. W(-3Bao/3Bao) embryos appeared pale after E14.5 and dwarf after E16.5. An extremely low level of hematochrome and large red blood cells were found in W(-3Bao/3Bao) 18.5 days old embryos, leading to the stillbirth of the homozygotes. In 18.5 days old embryos the spermatogonia of W(-3Bao/3Bao) embryos did not migrate to the contorted seminiferous tubules properly, but instead were found in the interstitial tissue. The spermatogonia of W(-3Bao/+) or W(+/+) mice were present in both the interstitial tissue and contorted seminiferous tubules. In the adult male hetereozygotes, there are contorted seminiferous tubules with no spermatogonia, suggesting that the migration defect was dominant. In female W(-3Bao/3Bao) ovaries, primordial follicles were absent while primordial follicles appeared clearly in the ovaries of W(-3Bao/+) or W(+/+) mice. With a nonsense mutation in the Kit gene, W(-3Bao/+) mice show white spotting and an abnormal development of the contorted seminiferous tubules and W(-3Bao/3Bao) mice are stillborn due to severe macrocytic anemia, and have abnormal genital glands in both the male and female.


Asunto(s)
Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Animales , Ratones , Fenotipo
10.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(5): 315-321, 2019 May 09.
Artículo en Zh | MEDLINE | ID: mdl-31091564

RESUMEN

Objective: To investigate the effect of overexpression of Notch intracellular domain (NICD) on proliferation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSC). Methods: The third generation hPDLSC with stable overexpressing of NICD were assigned as experimental group, normal hPDLSC were as negative control group and hPDLSC transfected with empty vector were as blank control group. The effect of overexpressing NICD on proliferation ability of hPDLSC was detected by using cell counting kit-8 (CCK-8). Alizarin Red staining and real-time quantitative PCR (qPCR) were used to detect the effects of NICD on cementum attachment proteins (CAP), osteocalcin (OCN), Runt-related transcription factor 2 (RUNX2) and Notch signal pathway receptor Notch1. The effect of overexpressing NICD on hPDLSC osteogenic protein RUNX2 and flag marker protein (used to label NICD) were detected by using Western blotting. Results: CCK-8 results showed that there were no significant differences in A values amongst the three groups for 1-2 days (P>0.05). The number of cells in the experimental group was significantly increase than that of the two control groups from the third to seventh days (A values were 0.203±0.016, 0.364±0.014, 0.449±0.020, 0.549±0.020 and 0.570±0.020, respectively) (P<0.05). Alizarin red staining showed that compared with the blank control group and negative control group, the mineralized nodules in the experimental group had smaller formation range and lighter color, and the differences were statistically significant (P<0.05). The expressions of CAP gene (0.751±0.058, 0.887±0.025), osteocalcin gene (0.592±0.051, 0.670±0.045) and RUNX2 gene (0.319±0.038, 0.684±0.055) at 14 and 21 days in the experimental group were significantly lower than those in the negative control group respectively (P<0.05). However, the expression levels of Notch1 gene at 14 and 21 days (2.507±0.047, 4.041±0.219) were significantly higher than those of negative and blank control groups (P<0.05). The results of Western blotting showed that the expressions of flag marker protein (0.167±0.007, 0.204±0.010) at 14 and 21 days in the experimental group were significantly higher than those in the negative and blank control groups (P<0.05). However, the expressions of RUNX2 protein (0.075±0.006, 0.074±0.013) at 14 and 21 days were significantly lower than that in the negative control group (0.092±0.003, 0.118±0.008) and blank control group (0.174±0.006, 0.212±0.008) (P<0.05). Conclusions: Overexpression of NICD can promote the proliferation capacity of hPDLSC and inhibit its osteogenic differentiation.


Asunto(s)
Proliferación Celular , Osteogénesis , Ligamento Periodontal , Diferenciación Celular , Células Cultivadas , Humanos , Ligamento Periodontal/citología , Células Madre
11.
Zhonghua Er Ke Za Zhi ; 56(8): 628-632, 2018 Aug 02.
Artículo en Zh | MEDLINE | ID: mdl-30078247

RESUMEN

Objective: To investigate the clinical, immunological, and molecular manifestations of nuclear factor kappa-B subunit 2 (NFκB2) gene mutation associated common variable immunodeficiency (CVID) . Methods: A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children's Hospital of Chongqing Medical University in December 2015. The clinical manifestations, biochemical tests, immunological function, molecular features, treatment, and follow-up of the patient were analyzed. The Chinese and PUBMED databases were searched with the key words "NFκB2" and "immune deficiency" and related literatures were reviewed. Results: The patient had 4 episodes of pneumonias and one otitis media since the age of 6 months. The serum immunoglobulin levels were IgG 2.73 g/L, IgA<0.07 g/L, and IgM 0.12 g/L. The percentage of peripheral lymphocyte subsets demonstrated increased CD3(+)T lymphocyte (81.8%), increased CD4(+) naïve T cell (39.1%), normal B cell (14.1%), low switched memory B and plasmablast B (respectively 0.1% and 0), and lightly diminished natural killer(NK) cell (4.13%). Within the peripheral CD4(+)T cells, the percentage of regulatory T cells (1.49% (control 4.08%)), T follicular helper (3.66% (control 11.0%)), and T helper 17 (9.65% (control 15.7%)) were decreased, while the percentage of T helper 2 (60.9% (control 46.5%)) was elevated. T lymphocyte proliferative response and T cell receptor repertoire diversity were normal. NK-cell cytotoxic activity was impaired. The whole-exome sequencing harbored a de novo heterozygous nonsense mutation in exon 22 (c.2557C>T; p. Arg853X) in the C-terminus of NF-κB2. The western blotting confirmed the decreased expression of NF-κB2 (p52) protein. The patient received intravenous immunoglobulin infusion monthly (400-600 mg/kg), followed by improvement of pulmonary infection. After searching the databases, a total of 28 cases (1 Chinese and 27 non-Chinese) were identified. There were 12 cases of nonsense mutation (5 were gain-of-function mutation), and 8 cases of missense and frameshift mutations, respectively. The main clinical manifestation was respiratory infection, followed by autoimmune diseases such as alopecia and trachyonychia. Fifteen cases developed adrenocorticotrophic hormone (ACTH) deficiency. Conclusions: NF-κB2 signaling pathway played an important role in T and B lymphocyte differentiation, and NK-cell cytotoxic activity. NFκB2 mutation should be considered in cases with recurrent infections, hypogammaglobulinemia, and decreased memory B cells and plasma cells, especially when combined with ACTH deficiency.


Asunto(s)
Inmunodeficiencia Variable Común , Mutación , Subunidad p52 de NF-kappa B , Agammaglobulinemia , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/genética , Inmunodeficiencia Variable Común/inmunología , Heterocigoto , Humanos , Lactante , Masculino , Subunidad p52 de NF-kappa B/genética , Secuenciación del Exoma
12.
Phytochemistry ; 43(1): 133-40, 1996 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8987508

RESUMEN

Five new carbazole alkaloids, clausines B, E, H, I and K, as well as 22 known compounds, were isolated from the stem bark of Clausena excavata. The structures were established from spectral data and chemical transformation. These compounds showed significant inhibition of rabbit platelet aggregation and caused vasocontraction. The crude methanol extract, partitioned layers and chromatographic fractions revealed the presence of promotive and inhibitive constituents, simultaneously. These results might explain the philosophy of use in Chinese medicine, in that the dose and content variation in a prescription produced different, promotive or inhibitive, effects on therapy.


Asunto(s)
Alcaloides/aislamiento & purificación , Plantas Medicinales/química , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Vasoconstrictores/aislamiento & purificación , Alcaloides/química , Alcaloides/farmacología , Animales , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Medicina Tradicional China , Estructura Molecular , Inhibidores de Agregación Plaquetaria/química , Inhibidores de Agregación Plaquetaria/farmacología , Conejos , Espectrofotometría Ultravioleta , Vasoconstrictores/química , Vasoconstrictores/farmacología
13.
Phytochemistry ; 49(7): 2001-3, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9883591

RESUMEN

The continuing investigation of the root of Rhinacanthus nasutus afforded a 1,4-naphthoquinone ester, rhinacanthin-Q, accompanied by twenty-four known compounds. The structure was elucidated on the basis of spectroscopic analyses. The cytotoxicity and antiplatelet effect of this compound was also discussed.


Asunto(s)
Naftoquinonas/aislamiento & purificación , Naftoquinonas/farmacología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Plantas Medicinales/química , Humanos , Células KB/efectos de los fármacos , Naftoquinonas/química , Resonancia Magnética Nuclear Biomolecular , Extractos Vegetales/química , Raíces de Plantas/química , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología
14.
J Pharm Sci ; 72(6): 587-92, 1983 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-6875815

RESUMEN

The extended Hildebrand solubility approach was used to reproduce the solubilities of p-hydroxybenzoic acid in a dioxane-water system. The solubility parameter of p-hydroxybenzoic acid was determined and found to be approximately 15 (cal/cm3)1/2. Residual plots (scattergrams) were used in conjunction with R2, F, and standard deviation values to determine whether a quadratic, cubic, quartic, or higher degree polynomial was required in the calculations. The earlier iteration method for back-calculations of solubilities was replaced by the more reliable root-finder method. The solubility profile of p-hydroxybenzoic acid in dioxane-water mixtures did not follow a log linear relationship even in the ranges where the solubility parameters of the water-cosolvent mixture might be expected to produce a straight-line function, as observed in other studies.


Asunto(s)
Hidroxibenzoatos/análisis , Parabenos , Fenómenos Químicos , Química , Dioxanos , Estabilidad de Medicamentos , Cinética , Solubilidad , Solventes , Agua
15.
J Pharm Sci ; 73(2): 179-88, 1984 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6707879

RESUMEN

An expanded solubility parameter system was tested in conjunction with the extended Hansen solubility approach and the UNIFAC method to calculate the solubilities of naphthalene and benzoic acid in polar and nonpolar solvents. The expanded parameter system is characterized by delta d for the dispersion force, delta p for dipolar forces, a basic or electron-donor parameter, delta b, and an acidic or electron-acceptor parameter delta a. The correlation between the calculated and observed solubilities of benzoic acid was increased by use of the four-parameter system. An indicator variable was required to bring the solubilities into line in strongly dipolar solvents such as N,N-dimethylformamide. For naphthalene, use of the four-parameter approach proved not to be an improvement over the three-parameter extended Hansen solubility approach. The UNIFAC method was not successful in calculating solubilities of benzoic acid in the 40 polar and nonpolar solvents. A triangular plot of the three Hansen parameters for benzoic acid, p-hydroxybenzoic acid, and methyl p-hydroxybenzoate illustrated the contributions of dispersion, dipolar, and Lewis acid-base (hydrogen bonding) interaction forces among the three benzoic acid compounds and the various classes of solvents. A multiple regression procedure for calculating the four partial solubility parameters of drug solutes was developed.


Asunto(s)
Benzoatos , Naftalenos , Ácido Benzoico , Calorimetría , Fenómenos Químicos , Química Física , Modelos Químicos , Solubilidad , Solventes
16.
J Pharm Sci ; 73(2): 188-94, 1984 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6707880

RESUMEN

The recently introduced four-parameter extended Hansen approach was used to study the solubility of p-hydroxybenzoic acid and methyl p-hydroxybenzoate in 32 and 35 individual solvents, respectively. The results are compared with those for benzoic acid in 40 solvents. Seventeen of the thirty-two or 53% of the calculated solubilities of p-hydroxybenzoic acid were within the established solubility criterion (i.e., less than 30% error from the experimental value). Twenty-two of thirty-six or 61% of the calculated solubility values for methyl p-hydroxybenzoate met the solubility criterion. Experimental excess free energies of solution for p-hydroxybenzoic acid and methyl p-hydroxybenzoate were plotted against theoretical values using the expanded four-parameter solubility regression equations. From such results, adjustments may be made in the partial solubility parameters to bring the calculated solubilities in line with experimental results. Multiple regression analyses were used to estimate the total solubility parameter and the four partial solubility parameters of the two benzoic acid derivatives. Satisfactory results were obtained for methyl p-hydroxybenzoate, but poor agreement was found for p-hydroxybenzoic acid for the total parameter when compared with the Fedors group contribution method. Both the multiple regression and group contribution methods may yield inaccurate solubility parameters for relatively polar solid solutes. Factor analysis was used to test the adequacy of three- and four-parameter approaches in the evaluation of drug solubility. A principal factor method without iteration and orthogonal factor rotation were used to compare the two expanded solubility parameter approaches.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Hidroxibenzoatos , Parabenos , Fenómenos Químicos , Química Física , Análisis Factorial , Modelos Químicos , Solubilidad , Solventes , Termodinámica
17.
J Pharm Sci ; 71(11): 1285-7, 1982 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7175725

RESUMEN

A multiple linear regression method, known as the extended Hansen solubility approach, was used to estimate the partial solubility parameters, delta d, delta p, and delta h for crystalline solutes. The method is useful, since organic compounds may decompose near their melting points, and it is not possible, to determine solubility parameters for these solid compounds by the methods used for liquid solvents. The method gives good partial and total solubility parameters for naphthalene; with related compounds, less satisfactory results were obtained. At least three conditions, pertaining to the regression equation and the solvent systems, must be met in order to obtain reasonable solute solubility parameters. In addition to providing partial solubility parameters, the regression equations afford a calculation of solute solubility in both polar and nonpolar solvents.


Asunto(s)
Solubilidad , Fenómenos Químicos , Química Física , Naftalenos , Solventes , Temperatura
18.
J Pharm Sci ; 74(3): 277-82, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-4009435

RESUMEN

The extended Hildebrand solubility approach is used to estimate the solubility of sulfonamides in binary and ternary solvent systems. The solubility of sulfisomidine in the binary solvent, dioxane-water, shows a bell-shaped profile with a solubility maximum well above the ideal solubility of the drug. This is attributed to solvation of the drug with the dioxane-water solvent, and indicates that the solute-solvent interaction energy (W) is larger than the geometric mean (delta 1 delta 2) of regular solution theory. The solubilities of sulfadiazine, sulfisomidine, sulfathiazole, and sulfamethoxazole were determined in mixtures of dimethylacetamide, glycerol, and water, and the solubility profiles were well reproduced by use of the extended Hildebrand solubility approach. Since the solubility parameter (delta 1 = 11) of the solvent (dimethylacetamide) was approximately equal to the solubility parameters of the sulfonamides, and because of the powerful solvating power of dimethylacetamide, the solubility profiles did not exhibit peaks as observed for sulfisomidine in dioxane-water. When sulfisomidine was dissolved in a ternary mixture, i.e., butyl acetate (delta 1 = 8.5), dimethylacetamide (delta 1 congruent to 11), and methanol (delta 1 = 14.5), a spike was produced in the solubility profile at the solubility parameter of dimethylacetamide. This sharply peaked profile suggests that the two branches be treated as separate solubility curves, which are then independently well reproduced by the extended Hildebrand solubility approach. None of the four sulfonamides yielded log-linear relationships in the ternary mixtures.


Asunto(s)
Sulfonamidas/análisis , Acetamidas , Acetatos , Fenómenos Químicos , Química Física , Dioxanos , Metanol , Solubilidad , Solventes , Agua
19.
J Pharm Sci ; 74(6): 638-42, 1985 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-3839531

RESUMEN

In nonpolar solvents a solute may self-associate through polar interactions, exposing its nonpolar surface to a solvent with a low solubility parameter, delta 1. In polar solvents a solute is solvated, presumably, by the polar groups of the solvent. This "chameleonic" effect results in different solubility parameters for a solute, depending on the polarity of the solvent. This report presents data for solute solubility parameters in solvents of variable polarity and gives suggestions for dealing with the chameleonic effect associated with solute-solvent interaction.


Asunto(s)
Solubilidad , Solventes , Benzoatos , Ácido Benzoico , Alcohol Bencilo , Alcoholes Bencílicos , Fenómenos Químicos , Química Física , Densitometría , Modelos Teóricos , Peso Molecular , Programas Informáticos , Teofilina
20.
J Pharm Sci ; 71(12): 1334-40, 1982 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7153879

RESUMEN

Solubilities of testosterone and testosterone propionate in binary solvents composed of the inert solvent, cyclohexane, combined with the active solvents, chloroform, octanol, ethyl oleate, and isopropyl myristate, were investigated with the extended Hildebrand solubility approach. Using multiple linear regression, it was possible to obtain fits of the experimental curves for testosterone and testosterone propionate in the various binary solvents and to express these in the form of regression equations. Certain parameters, mainly K and log alpha 2, were employed to define the regions of self-association, nonspecific solvation, specific solvation, and strong solvation or complexation.


Asunto(s)
Testosterona , Química Farmacéutica , Cloroformo , Cristalización , Ciclohexanos , Modelos Químicos , Solubilidad , Solventes
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