ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

Objective To develop an oxybutynin nanotransdermal formulation with high skin permeability based on cubsomes carrier.Methods The oxybutynin loaded cubsomes(OXY-CS)was prepared by ultrasonic method.Using particle size,polydispersity index and encapsulation efficiency as evaluation indexes,stirring temperature,stirring time,stirring speed,ultrasound time,ultrasound power,glycerol monooleate/poloxamer 407 ratio(GMO/F127),carrier(GMO+F127)/drug ratio and drug concentration were optimized.The effects of drug concentration,permeation promoter and gel matrix type on skin permeability were investigated using cumulative permeation and skin retention as evaluation indicators.Results The prepared OXY-CS had small particle size and high encapsulation efficiency at stirring temperature of 50℃,stirring time of 30 min,stirring speed of 1 000 r/min,ultrasound time of 10 min,ultrasound power of 100 W,GMO/F127 ratio of 2∶1,carrier/drug ratio of 3∶1 and drug concentration of 1％,respectively.OXY-CS had high cumulative penetration and skin retention at concentration ≥ 3％.The addition of a permeation promoter to OXY-CS did not increase the cumulative penetration of the drug.The skin permeability of oxybutynin cubsomes gel made with carbomer was significantly better than those of other gel matrices.Conclusion In this study,oxybutynin is made into a topical cubsomes gel,which is expected to reduce the incidence of adverse effects associated with oral administration.

Objective To prepare propranolol hydrochloride loaded cubosomes (PPL-Cubs) with high entrapment efficiency. Methods PPL-Cubs was prepared by pH gradient method. Pressure and cycles of high pressure homogenization, dosage of glyceryl monooleate and poloxamer 407 were optimized to prepare blank cubosomes with particle size and polydispersity index as the indexes. The influences of various factors, including exterior pH values, internal pH values, the ratio of carrier to drug, particle size and polydispersity index of blank cubosomes, incubation temperature and time, and drug concentration on the entrapment efficiency were investigated. Results The blank cubosomes with small particle size and polydispersity index was prepared under homogenization conditions of 900 bar for 7 cycles, glyceryl monooleate dosage of 25%, and poloxamer 407 dosage of 5%. PPL-Cubs showed high entrapment efficiency with exterior pH value of 8.5, internal pH value of 3.0, ratio of carrier to drug of 6∶1, incubation temperature of 20 ℃, and incubation time of 15 min, and drug concentration of 1%. The particle size and polydispersity index of blank cubosomes showed no influence on entrapment efficiency. Conclusion PPL-Cubs with high entrapment efficiency could be prepared under the pH gradient method.

Objective To establish the quality control methods for Qihuang Fuzheng particle .Methods Astragali Ra-dix ,Rehmanniae Radix Praeparata ,Corni Fructus ,Chuanxiong Rhizoma ,Angelicae Sinensis Radix , Paeoniae Radix Rubra ,Moutan Cortex ,and Ophiopogonis Radix were identified with TLC .HPLC method was used for loganin assay in Cor-ni Fructus .Results TLC identification methods for the main components were established .The TLC spots were clear with good separation .No interference was detected from the negative samples .The peak response and concentration of loganin showed good linear relationship over the range of 4 .02-80 .40 μg/ml (r=0 .9999) .The mean recovery of loganin was 99 .02％(RSD=0 .64％ ,n=9) .Conclusion The established quality control methods are accurate ,reliable ,and specific ,which lay a foundation for the quality control of Qihuang Fuzheng particle .

Objective:To establish the quality control methods for Qianliedan particle. Methods:TLC was used to identify Scutel-lariae Barbatae Herba, Astragali Radix, Glycyrrhizae Radix Et, Rhizoma Praeparata Cum Melle, Psoraleae Fructus and Curcumae lon-gae Rhizoma. The content determination item was developed by determining the content of scutellarin in Scutellariae Barbatae Herba by HPLC. Results:The TLC spots were clear and well-separated without any interference from the negative sample. A good linear rela-tionship was established between the peak response and the concentration of scutellarin within the range of 3. 96-79. 20 μg·ml-1(r=0. 999 9). The mean recovery of scutellarin was 99. 34% (RSD=1. 25%, n=9). Conclusion:The established quality control meth-ods are accurate, reliable, stable and specific, which can be well used for the quality control of Qianliedan particle.

Objective To study and establish the extraction technology of hypoglycemic components of total flavonoids and polysaccharides from Gynura divaricata (L .) DC ..Methods Based on the singer factor test ,the influences of extracting times ,diameter of drug powder ,soaking time ,solid-liquid ratio ,ethanol concentration ,and extracting time on extraction ratio of total flavonoids were studied .The best extraction technology of total flavonoids from Gynura divaricata (L .) DC .was es-tablished through L9 (3)4 orthogonal tests .On the base of previous studies combine with L9 (3)4 orthogonal tests ,the best ex-traction technology of total polysaccharides from Gynura divaricata (L .) DC .was established .Results The optimized extrac-tion technology of total flavonoids was confirmed as follows :drug powder of less than 10 mesh diameter were soaking 0 .5 hour with 80% ethanol ,and solid-liquid ratio 1∶20 ,and extracting twice ,each time one hour .The optimized extraction technology of total polysaccharides was confirmed as follows :add 20 times water to the residue of ethanol ,extraction temperature 90℃ , and extracting twice ,each time one hour .The extraction rate of both total flavonoids and polysaccharides were more than 80% .Conclusion The extraction technology of hypoglycemic components of total flavonoids and polysaccharides from Gynura divaricata (L .) DC .established in this study is stable ,reproducible ,and lays a foundation for the further studies on hypogly-cemic components in Gynura divaricata (L .) DC .