Oral Preparations Research Articles

Comparison of ciprofloxacin, cotrimoxazole, and doxycycline on Klebsiella pneumoniae: Time-kill curve analysis.

Antibiotic resistance is a significant problem in the world, so optimization of antibiotic use is needed. Klebsiella pneumoniae is a Gram-negative bacterium that causes bacteremia, sepsis, UTIs, pneumonia, nosocomial infections and ESBL-producing bacterium. ciprofloxacin, cotrimoxazole, and doxycycline are broad-spectrum antibiotics, including in WHO essential drugs. The study tested antibiotics that most effectively inhibited Klebsiella pneumoniae non-ESBL, Klebsiella pneumoniae ESBL invitro with time-kill curve analysis. This experiment used Klebsiella pneumoniae ATCC isolates, stored clinical isolates of Klebsiella pneumoniae non-ESBL, Klebsiella pneumoniae ESBL, and the control group. Isolates other than control were challenged with ciprofloxacin, cotrimoxazole, and doxycycline oral preparations with concentrations of 1, 2, 4 MIC at 0, 2, 4, 6, 8, 24h. At each hour, the bacteria were cultured, incubated, calculated the number of colonies. The results were analyzed with time-kill curve and tested statistics. Statistical analysis used included ANOVA, post-Hoc, Mann Whitney, and Kruskal Willis tests with p<0.05. Ciprofloxacin, cotrimoxazole, and doxycycline in this study had inhibition effects on Klebsiella pneumoniae non-ESBL and Klebsiella pneumoniae ESBL. Ciprofloxacin had the best inhibitory effect. Statistically, the most meaningful differences of antibiotics in ciprofloxacin and cotrimoxazole at four and 24h (p<0.001), in concentrations of 1 MIC and 4 MIC at 2h (p<0.001), and in Klebsiella pneumoniae ESBL and Klebsiella pneumoniae ATCC at 8h (p=0.024). Ciprofloxacin is the best antibiotic to inhibit the growth of Klebsiella pneumoniae non-ESBL and Klebsiella pneumoniae ESBL compared to cotrimoxazole and doxycycline. The inhibitory effect increases with an increase in concentration.

Mechanical and oral antibiotics bowel preparation for elective rectal cancer surgery: A propensity score matching analysis using a nationwide inpatient database in Japan.

The best bowel preparation method for rectal surgery remains controversial. In this study we compared the efficacy and safety of mechanical bowel preparation (MBP) alone and MOABP (MBP combined with oral antibiotic bowel preparation [OABP]) for rectal cancer surgery. In this retrospective study we analyzed data from the Japanese Diagnosis Procedure Combination (DPC) database on 37 291 patients who had undergone low anterior resection for rectal cancer from 2014 to 2017. Propensity score matching analysis was used to compare postoperative outcomes between MBP alone and MOABP. A total of 37 291 patients were divided into four groups: MBP alone: 77.7%, no bowel preparation (NBP): 16.9%, MOABP: 4.7%, and OABP alone: 0.7%. In propensity score matching analysis with 1756 pairs, anastomotic leakage (4.84% vs 7.86%, P < 0.001), small bowel obstruction (1.54% vs 3.08%, P=0.002) and reoperation (3.76% vs 5.98%, P=0.002) were less in the MOABP group than in the MBP group. The mean duration of postoperative antibiotics medication was shorter in the MOABP group (5.2d vs 7.5d, P < 0.001) than in the MBP group. There was no significant difference between the two groups in the incidence of Clostridium difficile (CD) colitis (0.40% vs 0.68%, P=0.250) and methicillin-resistant Staphylococcus aureus (MRSA) colitis (0.11% vs 0.17%, P=0.654). There was no significant difference in in-hospital mortality between the two groups (0.00% vs 0.11% respectively, P=0.157). MOABP for rectal surgery is associated with a decreased incidence of postoperative complications without increasing the incidence of CD colitis and MRSA colitis.

Dissolution Effectiveness of Moringa Leaf Pills (Moringa Oleifera L.) and Aloe Vera (Aloe Barbadensis Miller)

Oral preparations with level solubility tall so speed dissolution substance active from form preparations Becomes more fast, anyway with preparations with speed dissolution low so speed dissolution substance active from form preparations Becomes slow, so rate absorption drug more slow as well as produce bioavailability low. Materials potion drug traditional for example from ingredient plant natural around which not yet experience processing whatever. Ingredient nature used _ as drug traditional in study this is plant leaf moringa and tongue crocodile. Leaf Moringa (Moringa oleifera L.) has various type effect therapy like antimicrobial, anticancer, anti-inflammatory, effect antidiabetic as well as as antioxidants. Compound chemical in the leaves _ moringa that is there is polyphenols, acids phenolics, flavonoids, glucosinolates, alkaloids, vitamins, acids phenolics, isothiocyanates, tannins and saponins. Plant tongue crocodile (Aloe barbadensis Miller). kindly chemistry, tongue crocodile consists over 90% water and 4% carbohydrates, the rest consists of minerals, 17 kinds amino acids. Gel found on the tongue crocodile there is content substance antibacterial as well as possible antifungal _ stimulate tiroblast . Study this aim for knowing effectiveness dissolution pill from leaf moringa and tongue crocodile with use method study experimental. Result of study this yield extract leaf moringa and tongue crocodile obtained on the leaves moringa by 6.38% and tongue crocodile 6.268%. Assessment test preparations pill Fulfill condition uniformity weight and fulfill dissolution test conditions because time the required crush for 30 minutes.

Iron deficiency and postcovid syndrome: a clinical case

Postcovid syndrome is a serious public health problem affecting millions of people worldwide. There is a growing body of evidence that people may exhibit symptoms after organ damage developed during the acute phase of COVID‑19, while others experience new symptoms after a mild infection, without any evidence of acquired organ or tissue damage. In this regard, understanding the determinants and regulators of COVID‑19 and postcovid syndrome pathology is an important clinical challenge that will enable better management of future variants and pandemic waves. There is presumably a close relationship between iron homeostasis, COVID‑19, and postcovid syndrome, the pathogenetic aspects of which have yet to be determined. Nevertheless, the available literature already indicates that iron deficiency and iron deficiency anemia (without inflammatory anemia) in patients with postcovid syndrome occur in 30% and 9% of cases, respectively. Given the importance and urgency of this problem and the fact that one in three patients with postcovid syndrome may have iron deficiency, this article presents a case from clinical practice in which a patient with postcovid syndrome was found to have iron deficiency and iron deficiency anemia, and treatment of this condition and disease resulted in improvement in general well-being and regression of symptoms. Thus, the effects of COVID‑19 on iron metabolism exist, and they can be corrected. The use of oral iron preparations, in particular iron sulfate, allows optimal therapeutic and clinical effects in this clinical situation along with a good tolerability and safety profile.

Залізо: біохімічні, фармакологічні, клінічні дані

Iron is one of the most important macroelements in the body, which takes part in oxidation-reduction processes, and bioenergetics, and is a part of a number of enzymes. Iron deficiency is associated with food, pregnancy, fetal development, and some diseases. First of all, iron deficiency is established in iron-deficiency anemia, in addition to violations of biochemical indicators, immunological shifts and changes in the activity of vital organs and systems. The purpose of the study was to analyze the properties of iron and its preparations and their effects on the body. Materials and methods. On the topic of the study, a search and analysis of scientific literature was conducted in such databases as PubMed, Google Scholar, Scopus. Results and discussion. Iron reserves in the body are 3–6 g, the daily requirement is 20–30 mg. The need for iron increases in diseases with an increase in cardiac output, an increase in temperature, which requires taking drugs for oral and parenteral administration. In addition, if it is necessary to replenish iron reserves, it is recommended to take extracts from plants that contain it, such as common apricot (fruit pulp), blueberry fruits, beet roots, and common peach fruits. At the same time, it should be noted that iron can be in the oxidizing form of Fe2+ and the reduced form of Fe3+. It was determined that changes in iron metabolism and transport occur in pregnant women, which, in turn, is associated with changes in endothelial protective function. In modern methodological recommendations for the treatment of chronic heart failure, iron preparations are also included in the list of mandatory drugs, because in this condition, in addition to iron deficiency, disorders of the functions of the cardiovascular system have been found. A decrease in iron content has also been determined in various hypoxic conditions. Next they showed changes in iron metabolism in infectious diseases, such as COVID-19, tuberculosis, and HIV infection. In recent years, changes in iron content in neurodegenerative diseases have been noticed. Today, there are oral and parenteral iron preparations, but research is underway to create iron preparations that may have a more targeted effect and less toxicity. Conclusion. The current state of iron research in the functioning of vital organs and the occurrence of diseases presents scientists and clinicians with the task of involving new experimental and clinical methods to expand the understanding of the role of iron in pathobiochemical mechanisms, in pathological conditions, as well as the search for new approaches to treatment

Association of bowel preparation with surgical-site infection in gynecologic oncology surgery: Post-hoc analysis of a randomized controlled trial

ObjectiveTo determine the relationship between bowel preparation and surgical-site infection (SSI) incidence following colorectal resection during gynecologic oncology surgery. MethodsThis post-hoc analysis used data from a randomized controlled trial of patients enrolled from 03/01/2016–08/20/2019 with presumed gynecologic malignancy investigating negative-pressure wound therapy among those requiring laparotomy. Patients were treated preoperatively without bowel preparation, oral antibiotic bowel preparation (OABP), or OABP plus mechanical bowel preparation (MBP) per surgeon preference. Univariate and multivariable analyses with stepwise model selection for SSI were performed for confirmed gynecologic malignancies requiring colorectal resection. ResultsOf 161 cases, 15 (9%) had no preparation, 39 (24%) OABP only, and 107 (66%) OABP+MBP. The overall SSI rate was 19% (n = 31)—53% (n = 8/15) in the no preparation, 21% (n = 8/39) in the OABP alone, and 14% (n = 15/107) in the OABP+MBP groups (P = 0.003). The difference between OABP and OABP+MBP was non-significant (P = 0.44). The median length of stay was 9 (range, 6–12), 6 (range, 5–8), and 7 days (range, 6–10), respectively (P = 0.045). The overall complication rate (34%; n = 54) did not significantly vary by preparation type (P = 0.23). On univariate logistic regression analysis, OABP (OR, 0.23; 95% CI: 0.06–0.80) and OABP+MBP (OR, 0.14; 95% CI: 0.04–0.45) were associated with decreased SSI risk compared to no preparation (P = 0.004). On multivariate analysis, both methods of preparation retained a significant impact on SSI rates (P = 0.004). ConclusionBowel preparation is associated with reduced SSI incidence and is beneficial for patients undergoing gynecologic oncology surgery with anticipated colorectal resection. Further investigation is needed to determine whether OABP alone is sufficient.

Directions of hyaluronic acid application in cosmetology.

Hyaluronic acid is a naturally occurring substance in the human body. It is a component of the intercellular matrix of the dermis and is often used as a raw material in cosmetology. This substance was isolated for the first time in the first half of the twentieth century, while cosmetology treatments and aesthetic medicine have been developing rapidly and gaining popularity. The same applies to companies producing cosmetic care products which contain hyaluronic acid. This is related to the growing desire of the society to improve the quality of the skin and maintain its vitality and firmness. The study investigates different directions and possibilities of using hyaluronic acid in cosmetology. Moreover, the paper describes possible side effects observed after hyaluronic acid injections. The study was based on an anonymous questionnaire conducted between October 10, 2021, and February 21, 2022. 513 responses were collected. The awareness and level of knowledge in this field of cosmetology among potential beauty salon clients are on the rise. Hyaluronic acid is used in injections, as well as in care cosmetics, oral and vaginal preparations. Various areas of the face are injected, most often the lips. Face creams are among the most frequently purchased skincare products. The use of hyaluronic acid in cosmetology is multidirectional. It is mainly focused on skincare and specific anti-aging activities. Treatments of this type help preserve the skin's vitality, which translates into an improved quality of life due to the satisfaction of the need for attractiveness.

AQbD based green UPLC method to determine mycophenolate mofetil impurities and Identification of degradation products by QToF LCMS

We report an ideal method for quantifying impurities in mycophenolate mofetil drug substances and their oral suspension preparations. We developed a systematic and eco-friendly analytical approach utilizing quality by design (QbD) and green chemistry principles. Initially, the critical method parameters (CMPs) were screened using a D-optimal design. The robust final method conditions were optimized using a systematic central composite design (CCD). Through graphical and numerical optimization, the protocol conditions were augmented. The pH of mobile phase buffer (25 mM KH2PO4) (MP-A), initial gradient composition (% MP-A), flow rate (mL min−1), and column oven temperatures (°C) are 4.05, 87, 0.4, and 30, respectively. The best possible separation between the critical pairs was achieved while using the Waters Acquity UPLC BEH C18 (100 × 2.1) mm, 1.7 µm analytical column. A mixture of water and acetonitrile in the ratio of 30:70 (v/v) was used as mobile phase-B for the gradient elution. The analytical method was validated in agreement with ICH and USP guidelines. The specificity results revealed that no peaks interfered with the impurities and MPM. The mean recovery of the impurities ranged between 96.2 and 102.7%, and the linearity results r > 0.999 across the range of LOQ – 150%. The precision results (%RSD) ranged between 0.8 and 4.5%. The degradation products formed during the base-induced degradation were identified as isomers of mycophenolic acid and sorbitol esters using Q-ToF LC–MS and their molecular and fragment ion peaks. The developed method eco-friendliness and greenness were assessed using analytical greenness (AGREE), green analytical procedure index (GAPI), and analytical eco score, and found it is green.

Transdermal drug delivery system of domperidone sustained-release coated microsphere gels: In vitro characterization and in vivo evaluation

Domperidone (DMP) is an effective peripheral D2 dopamine receptor antagonist. It is commonly used in the treatment of nausea and vomiting caused by Parkinson's disease. An oral preparation, which is rapidly absorbed after administration, and reaches a peak plasma concentration within 15–30 min, is commonly used. However, owing to the “first-pass effect” of liver metabolism and intestinal wall metabolism, the oral bioavailability of domperidone is low, and the action period is long. Therefore, in the present study, spray drying and emulsion solvent evaporation were combined to prepare a coated microsphere preparation with sustained release effect, and a gel matrix was selected to prepare a sustained-release coated microsphere gel for transdermal drug delivery. The pharmacokinetic results showed that the transdermal sustained-release coated microsphere gel effectively increased the Tmax, Cmax, T1/2, and AUC compared with those of an oral DMP group (P < 0.05), and the relative bioavailability was 3.2 times that of the oral DMP group. This indicates that the preparation was able to ameliorate the problems associated with a traditional oral DMP formulation. Therefore, the present study may provide a theoretical basis for the transdermal delivery of DMP sustained-release microspheres.

Effective delivery of quality markers in alcohol precipitation of Pudilan Xiaoyan Oral Liquid

Taking Pudilan Xiaoyan Oral Liquid as a demonstration, the effective delivery of quality markers in alcohol precipitation of Chinese medicine oral liquid preparations was studied. With the transfer rates of adenosine, corynoline, cichoric acid, baicalin, and wogonin as evaluation indexes, the effect of the density of concentrate before alcoholic precipitation, volume fraction of ethanol, stirring speed, temperature of concentrated solution, stirring time, alcohol concentration, alcohol precipitation time, alcoholic precipitation temperature, alcohol addition rate, and the pH of concentrate on the alcohol precipitation process was investigated by Plackett-Burman trial design, thus obtaining the key factors that influenced the alcohol precipitation process. The key factors were further optimized by Box-Behnken design to determine the optimal alcohol precipitation conditions. When the density of concentrate before alcoholic precipitation was 1.12 g·mL~(-1), the pH of concentrate was 6.86, and the alcohol concentration was 50.00%, the transfer rates of baicalin and wogonin were 91.86% and 87.78%, respectively. When the density of concentrate before alcoholic precipitation was 1.13 g·mL~(-1), the concentration of alcohol was 74.50%, and the alcoholic precipitation temperature was 17.0 ℃, the transfer rates of adenosine, corynoline, and cichoric acid were 85.95%, 71.62% and 83.19%, respectively. The method of optimizing alcohol precipitation techniques and determining the parameters of Pudilan Xiaoyan Oral Liquid by response surface methodology is reasonable and feasible, which provides guidance and experience for the effective delivery of quality markers in Chinese medicine oral liquid preparations.

Novel Self-Nanoemulsifying Drug Delivery System of Single Bulb Garlic: Stability, Toxicity, and Antiinflammation in 3T3-L1 Cells

Single bulb garlic (SBG) has the potential as an immunomodulator; however, it has low solubility and bioavailability. A lipid-based delivery system, that is, the self-nanoemulsifying drug delivery system (SNEDDS), offers a novel opportunity in drug delivery. SBG can be a suitable candidate for SNEDDS development. This research aims to describe the physical stability, toxicity test of the SNEDDS, and SNEDDS SBG potential as antiinflammation in 3T3-L1 cells. The SNEDDS is made with various ratios of concentrations of carrier oil, surfactants, and cosurfactants, namely, 0.50: 3.45: 0.96, and added with SBG extract (SBGE) of 20 mg/mL. The results of the response test of SNEDDS SBGE formulation indicate an average and standard deviation of emulsification time of 16.38±3.01 (second), pH 7.21±0.08, and transmittance of 98.40±0.23(%). The average nanoemulsion size is 14.333±0.416 nm, polydispersion index of 0.213±0.056, and zeta potential of -14.67±0.72 mV. The results of the physical stability test indicate no segregation, deposition, cracking, or creaming in all nanoemulsion samples and SNEDDS SBG. The MTT test in a dose of 62.5, 125, 250, 500, 100, 2000, and 4000 µg/mL suggests that the highest viability of the 3T3-L1 cells is at a dose of 2000 µg/mL, which is 97.83%±1.55%. Therefore, SNEDDS SBGE can be a potential candidate for oral preparation by increasing bioavailability and reducing toxicity in the 3T3-L1 cells. An antiinflammatory test on the TNF-𝛼 and IL-1𝛽 expressions influences the 3T3-L1 cells. the SNEDDS of SBGE has the potential to reduce the expression of TNF-𝛼 and IL-1𝛽 and increase IL-10 expression in the methylglyoxal-induced 3T3-L1 cells.

Losartan Potassium and Verapamil Hydrochloride Compound Transdermal Drug Delivery System: Formulation and Characterization.

In this study, we developed a sustained-release transdermal delivery system containing losartan potassium (LP) and verapamil hydrochloride (VPH). LP and VPH have low bioavailability and long half-life. Therefore, the development of an optimum administration mode is necessary to overcome these drawbacks and enhance the antihypertensive effect. A transdermal diffusion meter was used to determine the optimal formulation of LP-VPH transdermal drug delivery systems (TDDS). Based on in vitro results, a sustained-release patch was prepared. Physical characteristics, including quality, stickiness, and appearance, were evaluated in vitro, while pharmacokinetics and skin irritation were evaluated in vivo. The results showed that 8.3% polyvinyl alcohol, 74.7% polyvinylpyrrolidone K30, 12% oleic acid-azone, and 5% polyacrylic acid resin II provided an optimized TDDS product for effective administration of LP and VPH. Furthermore, in vitro and in vivo release tests showed that the system continuously released LP and VPH for 24 h. The pharmacokinetic results indicated that although the maximum concentration was lower, both the area under the curve from 0-time and the mean residence time of the prepared patch were significantly higher than those of the oral preparations. Furthermore, the prepared LP-VPH transdermal patch showed good stability and no skin irritation. The developed LP-VPH TDDS showed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it is an ideal formulation.

Deformable Nanovesicle-Loaded Gel for Buccal Insulin Delivery.

Deformable nanovesicles (DNVs) have been widely used in oral mucosal delivery studies of biomolecular drugs. However, their development for oral mucosal preparations has been limited by their physical and chemical instability, the need for small oral volumes, and the complexity of the oral microenvironment. This study aimed to develop a more suitable buccal delivery system for DNVs with improved storage stability. Preliminary stability studies investigated different gel types, the effects of different hydrophilic gel matrices, and matrix temperature sensitivity using DNVs loaded with insulin-phospholipid complex (IPC-DNVs). A temperature-sensitive gel encapsulating IPC-DNVs (IPC-DNV-TSG) prepared with 2% w/v gelatin was stable at 4 °C for three months and maintained an excellent hypoglycemic effect. The delivery efficiency of IPC-DNVs and IPC-DNV-TSG was compared using a TR146 cell model, revealing that cell viability remained high. Cellular uptake was slightly lower for IPC-DNV-TSG than for IPC-DNVs, but total transport did not differ significantly between the two groups, which may have been related to the viscosity of IPC-DNV-TSG and the hydrophilicity, cell adhesion properties, and biocompatibility of gelatin. Moreover, neither IPC-DNVs nor IPC-DNV-TSG induced significant mucosal irritation in rabbit tongue tissue sections. The study findings demonstrate a promising method for possible use as oral mucosal delivery of peptide drugs.

Effect of oral zoledronate administration on bone turnover in older women.

The aim of this work is to assess the safety and efficacy of two oral zoledronate preparations by determining their effects on bone resorption in healthy postmenopausal women. The preparations studied were zoledronic acid in enteric-coated capsules or a microparticle preparation of zoledronic acid in these capsules. Bone resorption was measured as β-C-telopeptideof type I collagen (CTX) in fasting serum. Separate cohorts, each of five women, were recruited and allocated in sequence to single doses of 20 mg, 40 mg, or 60 mg of oral zoledronate. Zoledronate 20 mg enteric capsules were well tolerated, reduced serum CTX by a median 51% at 1 week, but by only 17% at 1 month. Doses of 40 or 60 mg of this preparation produced APR and/or gastrointestinal symptoms in more than half of participants. With these doses, median CTX reduction at 1 week was >80%, ~70% at 1 month, but only ~30% at 6 months. Enteric capsules containing microparticles of zoledronate 20 mg reduced CTX by a median 53% at 1 week, with offset over 3 months. Two or three of these capsules dosed weekly reduced CTX by ~50% at 1 month, and by ~30% at 3 and 6 months. Oral zoledronate 20 mg circumvents the problem of APR symptoms but, even with multiple doses, the anti-resorptive effect is smaller and less sustained than with intravenous zoledronate. Probably a viable oral regimen of zoledronate dosing at intervals of weeks to months could be developed, but the advantage of infrequent dosing would be lost.

Research on pharyngeal bacterial flora in transoral atlantoaxial operation and the postoperative follow-up study

ObjectivesTo study the changes of bacterial flora after a series of preoperative oral disinfection and the postoperative recovery of nerve function of patients with craniovertebral junction disorders who were treated with transoral approach operations.MethodsThis research analyzed 20 cases collected from October 2009 to May 2010. All these patients were with CVJ disorders, including 8 males and 12 females, aged 2 to 66 (38.1 on average), and they were all treated with transoral approach operations. The mucosa samples of the posterior pharyngeal wall were sent for bacteria culture. These samples were collected by sterile cotton swabs at four crucial points, including 3 days before operation/before gargling, 3 days after continuous gargling/after anesthesia intubation on the day of operation, after intraoperative cleaning and washing of the mouth, and after intraoperative iodophor immersion. The microflora was stained by means of smear and further counted after an investigation by microscope. The neural function of patients was evaluated by the ASIA classification and the JOA scores. All patients but two with posterior stabilization performed respectively underwent transoral atlantoaxial reduction plate (TARP) fixation consecutively in the same sitting. A regular reexamination of cervical vertebra with lateral and open mouth X-ray, CT and MRI was conducted after operation to evaluate the reduction of atlantoaxial dislocation, internal fixation position, bone graft fusion, inflammatory lesions and tumor recurrence.ResultsThis bacteriological research showed that the mucosa of the posterior pharyngeal wall of all the patients was in a sterile state after a series of oral preoperative preparations and intraoperative iodophor disinfection, which was considered as type I incision. The bacterial culture results of the mucosa samples of the posterior pharyngeal wall collected at different time points showed significant differences (χ2 = 42.762, P = 0.000). All the patients had improvement in ASIA, and their neural functions were improved to different levels after operation. There was a significant difference in JOA scores before and after operation (t = 8.677, P = 0.000). Postoperative imaging examination showed that the atlantoaxial screw position was good and firm, and the CVJ disorders were treated appropriately.ConclusionIt is safe and effective to cut the posterior pharyngeal muscle layer and implant internal fixation by means of transoral approach.

Biopharmaceutical, preclinical pharmacokinetic and pharmaco-dynamic investigations of an orally administered novel 3-nbutylphthalide prodrug for ischemic stroke treatment

Ischemic stroke (IS) has been contributing in leading causes of disability and death worldwide and the cases are still increasing. In China, naturally sourced compound 3-n-butylphthalide (NBP) is widely applied in clinical practice for IS treatment with established evidences of efficacy and safety. However, NBP is an oily liquid at room temperature and has no active brain targeting ability, quite limiting its broader application in clinical practice. Via intravenous injection (i.v.) a prodrug compound (DB1) we previously developed deriving from NBP had dramatically enhanced the pharmacological effects, where however, this i.v. route still discount future patient compliance. As druggability of DB1 in oral administration has yet to be elaborated, the current study intended to systemically investigate its biopharmaceutical properties, so as to further consider clinical applicability of DB1 oral preparations. Additionally, pharmacokinetics and pharmacodynamics of DB1 via oral administered route were also studied, illustrating broad potential of further DB1 medicine development. After the derivation, aqueous solubility of DB1 improved 3∼400 folds compared with NBP in various pH media, and n-octanol/water partition coefficient kept in the range of 0∼2. In situ single-pass intestinal perfusion on rats showed effective permeability coefficient of DB1 over 10-2 cm/s. In contrast to NBP, oral administration of DB1 could display significant enhanced bioavailability in rats and achieve increased accumulation in brain tissues. As expected, DB1 effectively alleviated oxidative stress damage and reduced infarct volume on ischemia/reperfusion (I/R) modeled rats, resulting in reduced mortality. Additionally, this new prodrug did not add any safety concerns based on NBP. Therefore, biopharmaceutical results and preclinical pharmacodynamic evidences support the conclusion that an oral administration of DB1 may have a good potential for clinical IS treatment.

Advances in traditional Chinese medicine as adjuvant therapy for diabetic foot.

Diabetes mellitus (DM) is a complex disease that often causes multiple systemic complications that have become a major international public health problem. Diabetic foot (DF) is one of the severe and frequent chronic complications of DM due to vascular lesions and neuropathy. DF ulcers (DFU) affect approximately 15% of people with DM and are the leading cause of death and disability. The prevalence and recurrence of DF are worrisome, and morbidity and mortality are also on the rise, which poses a substantial socioeconomic burden. Treating DF is difficult for clinicians and requires multidisciplinary cooperation, combining local and systemic therapy to reduce amputation and case-fatality rates. Traditional Chinese Medicine (TCM) has received extensive attention due to noticeable therapeutic effects and few adverse reactions. In recent years, research on DF treatment by TCM has been increasing, and further progress has been made. TCM includes oral medication, injectable preparations, and adjuvant therapy. This article reviews the relevant research on TCM-related adjuvant therapy for DF. We describe current progress in TCM in terms of external application, acupuncture, massage, acupoint injection, foot bath, fumigation, and moxibustion, as well as the mechanisms involved.

Intelligent-Responsive Enrofloxacin-Loaded Chitosan Oligosaccharide–Sodium Alginate Composite Core-Shell Nanogels for On-Demand Release in the Intestine

Simple SummaryNovel pharmaceutical formulations are attracting interest in their potential to overcome the poor palatability and strong gastric irritation of enrofloxacin. To overcome the difficulty of treating intestinal Escherichia coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)–sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was designed and systematically evaluated. Scanning electron microscopy images revealed that enrofloxacin nanogels were incorporated into the nano-sized cross-linked networks. The physical state and molecular interaction among the components of the nanogel and the enrofloxacin were evaluated by Fourier transform infrared spectroscopy. Furthermore, their biocompatible structure, high drug loading efficacy, ideal stability, “on-demand” release at the target site, and antibacterial activity were confirmed. Thus, the present study may serve as a fruitful platform to explore nanogel to resolve the challenge of enrofloxacin formulation development and the fight against intestinal bacterial infections.Enrofloxacin has a poor palatability and causes strong gastric irritation; the oral formulation of enrofloxacin is unavailable, which limits the treatment of Escherichia coli (E. coli) infections via oral administration. To overcome the difficulty in treating intestinal E. coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)–sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was explored. The formulation screening, characteristics, pH-responsive performance in gastric juice and the intestinal tract, antibacterial effects, therapeutic effects, and biosafety level of the enrofloxacin composite nanogels were investigated. The optimized concentrations of COS, SA, CaCl2, and enrofloxacin were 8, 8, 0.2, and 5 mg/mL, respectively. The encapsulation efficiency, size, loading capacity, zeta potential, and polydispersity index of the optimized formulation were 72.4 ± 0.8%, 143.5 ± 2.6 nm, 26.6 ± 0.5%, −37.5 ± 1.5 mV, and 0.12 ± 0.07, respectively. Scanning electron microscopy images revealed that enrofloxacin-loaded nanogels were incorporated into the nano-sized cross-linked networks. Fourier transform infrared spectroscopy showed that the nanogels were prepared by the electrostatic interaction of the differently charged groups (positive amino groups (-NH3+) of COS and the negative phenolic hydroxyl groups (-COO−) of SA). In vitro, pH-responsive release performances revealed effective pH-responsive performances, which can help facilitate targeted “on-demand” release at the target site and ensure that the enrofloxacin has an ideal stability in the stomach and a responsive release in the intestinal tract. The antibacterial activity study demonstrated that more effective bactericidal activity against E. coli could have a better treatment effect than the enrofloxacin solution. Furthermore, the enrofloxacin composite nanogels had great biocompatibility. Thus, the enrofloxacin composite core-shell nanogels might be an oral intelligent-responsive preparation to overcome the difficulty in treating intestinal bacterial infections.

Expert consensus on the clinical diagnosis and targeted therapy of HER2 breast cancer (2023 edition).

Human epidermal growth factor receptor 2 (HER2) is an important driver gene and prognostic indicator of breast cancer and also a key predictor of HER2-targeted therapies. The emerging anti-HER2 drugs have greatly changed the diagnosis and treatment modalities of breast cancer and dramatically improved the prognosis of HER2-positive breast cancer patients. To optimize the treatment of HER2 breast cancer an update of expert consensus on HER2 positive breast cancer was made to adjust the different recommendation levels from early stage to metastatic stage. Meanwhile, antibody-drug conjugate (ADC) like trastuzumab deruxtecan (T-Dxd) has been shown to have great efficacy in HER2-positive and HER2 low expression breast cancer patients. Clinically, on the basis of the original definition for HER2-negative breast cancer, patients with HER2 immunohistochemistry (IHC) 1+ or IHC 2+ and in-situ hybridization (ISH)-negative are defined as low HER2 expression (HER2-low). As both the low expression and the positive expression of the HER2 protein is clinically significant for disease treatment and prognosis, we added a new chapter of HER2 low to recommend a proper regimen for this kind of patients. In this consensus, we also talk about the importance of clinical research, real world evidence, biosimilars and so on. In addition, the whole-course management of HER2 breast cancer is even more critical during pandemic of coronavirus disease 2019 (COVID-19). An approach that gives preference to "low-toxicity regimens and oral preparations" are also recommended.

S2632 Challenge a Diverticular Bleeding

Introduction: Colonic diverticular bleeding is the most common cause of acute LGI bleeding. Colonoscopy is recommended as the initial diagnostic modality. Although, the detection rate of the bleeding is variable as it is a challenging diagnosis Case Description/Methods: A 67 yo Man with a history of hypertension and diabetes mellitus, on baby aspirin presented to our emergency department with 4 episodes of painless hematochezia of 1day duration. The patient was initially stable but blood pressure dropped to 74/52 mmHg with continuous bleeding. Initial hemoglobin 12.5 g/dL dropped to 7.9 g/dL. A computed tomography (CT) scan showed intraluminal active arterial extravasation in the proximal transverse colon with scattered colonic diverticula. After IV resuscitation and blood transfusions, a selective and subselective angiography of the celiac axis and the superior mesenteric artery showed no evidence of active hemorrhage. Subsequent colonoscopy using a CF-HQ190L with an attached cap was performed, after oral preparation with 4 L of polyethylene glycol 3350. Multiple diverticula with medium openings were seen in the whole colon. Diverticula were washed and examined very carefully. One diverticulum in the transverse colon was noted with a visible clot. The base of the diverticulum was injected with epinephrine 1/10000 which inverted the diverticulum and exposed the culprit vessel. 3 endoclips were applied with successful hemostasis. The patient was followed and showed no recurrent hemorrhage. A repeat non-contrast CT showed the clips at the site of previous active extravasation (Figure 1). Discussion: Colonic diverticular bleeding accounts for 20.8 to 41.6% of LGI bleeding. After resuscitation, colonoscopy is recommended as an initial diagnostic modality. Although the detection rate of the bleeding varies from 6% to 42%. Detecting stigmata of recent bleeding is challenging, but improved if performing the colonoscopy urgently, within 24 h, with oral lavage solutions, by expert endoscopists who have performed >1,000 colonoscopies, and with the use of disposable distal attachments and water-jet systems. Having CT angio ahead of time is beneficial as it guides us anatomically. Therapeutic endoscopic options include clipping, epinephrine injection, band ligation or conservative management. Injecting the diverticulum with saline with or without epinephrine will invert the diverticulum and expose the inside including a clot or visible vessel and make hemostasis easier. This represents a new technique in diverticular bleeding control.Figure 1.: Diverticular bleeding control.