[Objectives]To enhance the skin permeability of hydroxypropyl tetrahydropyrantriol and provide a reference for the subsequent prevention or treatment of skin aging.[Methods]The lyophilization process of hydroxypropyl ...[Objectives]To enhance the skin permeability of hydroxypropyl tetrahydropyrantriol and provide a reference for the subsequent prevention or treatment of skin aging.[Methods]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was investigated using a single factor method,and a quality evaluation system was established based on the appearance,particle size,PDI,and re-dispersibility of the lyophilized samples.[Results]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was determined by single factor experiments.The pre-freezing period was 16 h at-80℃,the total drying time was 36 h,and the addition of 10%mannitol-sucrose was used as the lyoprotectant.[Conclusions]The product prepared by the lyophilization method exhibits a fluffy and full appearance,with minimal shrinkage and collapse.The volume remains consistent before and after lyophilization,and the re-dispersibility is satisfactory.The re-dissolution process is rapid,and the particle size and polydispersity index(PDI)remain largely unchanged before and after lyophilization.展开更多
Pre-freezing is an important stage in freeze-drying processes.For the lyophilization of a cell,freezing not only plays a role for primary dehydration,but it also determines the amount of residual(intracellular or extr...Pre-freezing is an important stage in freeze-drying processes.For the lyophilization of a cell,freezing not only plays a role for primary dehydration,but it also determines the amount of residual(intracellular or extracellular)water,which in turn can influence the solution properties and the choice of operation parameters.The freezing of human platelets in lyoprotectant solution is theoretically investigated here.A two-parameter model and an Arrhenius expression are used to describe cell membrane permeability and its temperature dependency.It is assumed that the intracellular solution is composed of four components:sodium chloride,trehalose,serum protein and water,while the extracellular solution consists of three components.Non-ideal solution behaviors are predicted using measured data.The concentration of maximally freeze-concentrated solution is estimated on the basis of an assumption of solute hydration.The impacts of lyoprotectant composition and extracellular sub-cooling on intracellular supercooling and residual water content in the cell are analyzed.The values of activation energy of hydraulic permeability at low temperatures are tested to study their impact on the critical cooling rate.As the mass fraction extracellular lyoprotectant(trehalose+bovineserum albumin)increases from 5 wt%to 20 wt%,the intracellular water content at the end of freezing does not change,but the intracellular solution undergoes much higher super-cooling degree.Increasing the mass ratio of trehalose to bovine serum albumin does not change the intracellular water content,but can mitigate intracellular super-cooling.While 0.05 mol/kg trehalose is loaded into platelet,the total quantity of residual water at the end of freezing may raise by 4.93%.The inclusion of dimethyl sulfoxide(Me2SO)in protectant may bring negative impacts to the drying stage by increasing the residual water content and lowering the drying temperature.展开更多
Freeze-drying or lyophilization is a multi-stage operation of effectively drying a material while preserving its biological properties.The material is subject to being frozen and sublimated under vacuum upon heating.L...Freeze-drying or lyophilization is a multi-stage operation of effectively drying a material while preserving its biological properties.The material is subject to being frozen and sublimated under vacuum upon heating.Lyophillized products are more stable,easily transported and quickly reconstituted.A benefit of low-temperature operation envisages its applications in pharmaceuticals for heat-sensitive components including vaccine and biological products.To date,analyses of the freeze-drying process have been changed from physical aspects of freezing and sublimation to a more sophisticated examination of the effects of the process on the chemical structures and the biological properties of the products themselves[1].展开更多
Nifedipine-solid-lipid nanoparticles lyophilized with trehalose (NI-SLN-Tre) were prepared by the high pressure homogenization of a roll mixture consisting of NI and hydrogenated soybean phosphatidylcholine and dipalm...Nifedipine-solid-lipid nanoparticles lyophilized with trehalose (NI-SLN-Tre) were prepared by the high pressure homogenization of a roll mixture consisting of NI and hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol, and in vivo pharmacokinetic properties and their hemocompatibility were determined and compared with those of a NI-SLN suspension. The resulting pharmacokinetic data demonstrated that although no significant differences were observed between the time of peak concentration (Tmax), peak plasma concentration (Cmax), and the area under the curve (AUC0→∞) values of both administrated samples, NI tended to be absorbed to a much greater extent from the lyophilized NI-SLN-Tre suspensions because of the enhanced solvation of NI-SLN in gastrointestinal fluid, derived from formation of hydrogen bonds between the polar head groups of the lipids and the O-H groups of trehalose. Furthermore, the results of a hemolysis assay revealed that the NI-SLN and NI-SLN-Tre suspensions showed good hemocompatibility properties with hemolysis values of less than 5%. Taken together, the results of this study demonstrate that NI-SLN-Tre exhibits suitable pharmacokinetic properties and good biocompatibility.展开更多
This paper reviewed the unique biological function of trehalose and its mechanism of stabilizing biological macromolecules and the research progress in the protective effect of trehalose on lactic acid bacteria fermen...This paper reviewed the unique biological function of trehalose and its mechanism of stabilizing biological macromolecules and the research progress in the protective effect of trehalose on lactic acid bacteria fermentation starters during lyophilization in food production.The application of trehalose in food industry was prospected.展开更多
Objectives: To improve the aqueous solubility and dissolution of fexofenadine HCl, an attempt was made to prepare its fast dissolving tablets by lyophilization technique. Methods: For the preparation of lyophilized ta...Objectives: To improve the aqueous solubility and dissolution of fexofenadine HCl, an attempt was made to prepare its fast dissolving tablets by lyophilization technique. Methods: For the preparation of lyophilized tablets (F1-F32), the drug was dispersed in a hydrated solution of water-soluble polymers (gelatin/maltodextrin/acacia) containing glycine and mannitol. The blend was pelted down into the patches of a blister pack, frozen down and then lyophilized. Different characterization parameters viz. differential scanning calorimetry, hardness, weight variation, X-ray diffraction (XRD), scanning electron microscopy (SEM), mercury porosimetry, solubility, wetting time and water absorption ratio, lyophilization tablet index, drug content, in vitro dissolution and stability were evaluated. Key findings: Tablets (F32) containing acacia were found to have fast disintegration and relatively higher mechanical strength with improved drug solubility. X-ray diffractogram and scanning electron micrograph indicated decrease in crystallinity of drug and a good porous structure property for prepared tablet, respectively. Dissolution study showed complete drug released within 5 min. Moreover, tablets (F32) were found to be stable for one month at 25 ± 2 °C/60 ± 5% relative humidity.展开更多
The aim of present study was to use QbD approaches to evaluate the effect of independent product variables and their interaction on particle size of sodium fluoride and then obtain the optimized experimental condition...The aim of present study was to use QbD approaches to evaluate the effect of independent product variables and their interaction on particle size of sodium fluoride and then obtain the optimized experimental condition for predefined particle size of sodium fluoride. The sodium fluoride is mainly used in dental preparation for delivering the fluoride ion to the tooth enamel for that nano-particle size is required. Nowadays the milling process is used to reduce the particle size. But that process has some limitations due to crystalline nature of sodium fluoride;for overcoming those limitations, lyophilization method is used. A 4<sup>3</sup> level full factorial design was used to study the significant influence of process and product variables i.e. 1) Concentration of sodium fluoride, 2) Concentration of PVP, 3) Sample volume, 4) Drying surface, on particle size of sodium fluoride. The experimental design result shows that independent product variables significantly modify the structure and improve particle size reduction of sodium fluoride.展开更多
In the probiotics manufacturing process,lyophilization damages the cell membrane of microorganisms,reducing their viability and delaying reactivation of their cellular metabolism.The growth phase of microorganisms at ...In the probiotics manufacturing process,lyophilization damages the cell membrane of microorganisms,reducing their viability and delaying reactivation of their cellular metabolism.The growth phase of microorganisms at the time of lyophilization is thought to significantly affect their viability during storage and reactivation in the intestine.However,no study has systematically investigated the differences in overcoming mechanisms in microorganisms harvested at different growth phases against lyophilization.Therefore,in this study,we comparatively assessed the resistance mechanism of Bifidobacterium animalis ssp.lactis and Lacticaseibacillus rhamnosus harvested at exponential and stationary growth phases.We found that B.animalis ssp.lactis and L.rhamnosus harvested at the stationary phase had shorter lag phase in growth and higher survival rates during storage than those harvested at the exponential phase.As a result of metabolome analysis,the cells harvested at the stationary phase accumulated trehalose and arabinose,which function as cryoprotectants and protect cells from lyophilization-induced damage.These findings could provide a basis for establishing a manufacturing protocol for lyophilized probiotics that can be rapidly reactivated in the intestine to achieve optimal metabolic activity and induce health benefits.展开更多
Objective To observe changes on membrane integrity and ultrastructure of human sperm after freeze-drying.Methods Semen samples from both normospermic donors（group A, n=15） and infertile men with abnormal sperm param...Objective To observe changes on membrane integrity and ultrastructure of human sperm after freeze-drying.Methods Semen samples from both normospermic donors（group A, n=15） and infertile men with abnormal sperm parameters（group B, n=15） were enrolled into this study. These samples were freeze-dried by using a freeze-drying method. The membrane integrity in the head and tail regions of individual spermatozoon was examined by using the combined hypo-osmotic swelling-eosin Y exclusion test. Sperm ultrastructure in groups A（n=3） and B（n=3） was observed by scanning electron microscopy（SEM）.Results After freeze-drying, all spermatozoa were types I（damaged both head and tail membranes） and III（damaged head membrane and intact tail membrane） membrane integrity in groups A and B. Type III of group B had lower value than that of group A（P〈0.01）. Under SEM, intact freeze-dried spermatozoa including abnormal morphology and normal-looking morphology were observed in both groups A and B. A few freezedried sperm heads had unsmooth or fuzzy surface. Isolated sperm heads, bent tails,broken sperm tails or fragmentary tails were more frequently seen in group B than those in group A.Conclusion Freeze-dried human spermatozoa could have intact structural components. However, freeze-drying resulted in severe damage on membrane integrity and ultrastructure of sperm. Samples from infertile men would have less resistance to freeze-drying.展开更多
Hybrid aerogels have been prepared by freeze-drying technique after mixing water dispersions of cellulose microfibers or cellulose nanofibers and silica(SiO2)of type SBA-15(2D-hexagonal).The prepared composites were c...Hybrid aerogels have been prepared by freeze-drying technique after mixing water dispersions of cellulose microfibers or cellulose nanofibers and silica(SiO2)of type SBA-15(2D-hexagonal).The prepared composites were characterized by different analysis techniques such as SEM,hot-filament,DMA,etc.These composites are compared to those previously prepared using nanozeolites(NZs)as mineral charge.The morphology studied by SEM indicated that both systems have different structures,i.e.,individual fibers for cellulose microfibers WP-based aerogels and films for nanofibrillated cellulose NFC-based ones....These differences seem to be driven by the charge of the particles,their aspect ratio and concentrations.These hybrid materials exhibit tunable thermal conductivity and mechanical properties.The thermal conductivity values range between^18 to 28 mW.m^-1.K^-1 and confirm the superinsulation ability of these fibrous aerogels.Synergism on the thermal insulation properties and mechanical properties was shown by adjunction of mineral particles to both cellulose-based aerogels by reaching pore size lower than 100 nm.It significantly reduces the thermal conductivity of the hybrid aerogels as predicted by Knudsen et al.Furthermore,the addition of mineral fillers to aerogels based on cellulose microfibers induced a significant increase in stiffness.展开更多
The main objective of the present work is to design aspirin nanoparticles loaded suppositories which will reduce the side effects caused by aspirin suppositories. Aspirin nanoparticles were prepared initially based on...The main objective of the present work is to design aspirin nanoparticles loaded suppositories which will reduce the side effects caused by aspirin suppositories. Aspirin nanoparticles were prepared initially based on ionic-gelation mechanism and lyophilized. The prepared nanoparticles were evaluated, and the results confirmed that Fa9 formulation was the best with greater drug entrapment efficiency. Aspirin suppositories were prepared in order to investigate the best base composition. The prepared suppositories were evaluated and FS1, FS3, FS4, FSS, FS1 l, and FS12 were proved to be the best base compositions based on dissolution performed. The lyophilized aspirin nanoparticles of Fa9 were used to prepare aspirin nanoparticles loaded suppositories. The in vitro results revealed that Fasl 1 was the best formulation.展开更多
Poly（Imino Ketone） （PIK） is a group of novel high performance polymer material with excellent thermal properties and dissolubility. Aiming at the requirements of inertial confined fusion （ICF） studies on low den...Poly（Imino Ketone） （PIK） is a group of novel high performance polymer material with excellent thermal properties and dissolubility. Aiming at the requirements of inertial confined fusion （ICF） studies on low density polymer foams, we firstly synthesized poly（imino imino ketone） （PIIK） by palladium catalyzed C-N cross-coupling reaction, and successfully prepared the PIIK foam material with a density of 80-300 mg/cm3 by using PIIK as the raw material with thermal-induced phase separation and lyophilization technique. Mercury injection method was used to determine the structure of PIIK foams, and the results indicated that the mean pore diameter was lower than 5 ~tm and it had relatively high voidage and specific surface area.展开更多
The shelf-life of a bioherbicide product is an important factor with regard to its commercial potential. The bioherbicidal efficacy of freshly fermented Myrothecium verrucaria (strain IMI 368023) (MV) mycelia formulat...The shelf-life of a bioherbicide product is an important factor with regard to its commercial potential. The bioherbicidal efficacy of freshly fermented Myrothecium verrucaria (strain IMI 368023) (MV) mycelia formulations and MV mycelia preparations that had been freeze-dried and then stored at -20°C for 8 years was compared. Two concentrations of each formulation (1.0x and 0.5x) were tested, utilizing bioassays on seedlings of the weed, hemp sesbania (Sesbania exaltata) under greenhouse conditions or in darkness utilizing hydroponically grown seedlings. Freeze drying of freshly prepared MV mycelium produced a light, brownish-colored powder. Efficacy tests of this reconstituted 8-year-old dried material showed that some bioherbicidal activity was lost during long-term storage, i.e., ~20% and ~60% seedling dry weight reduction at the 1.0x and 0.5x rate, respectively. Although plant mortality was greater in the fresh mycelial preparations treatments versus the freeze-dried and stored samples at all time points in the time-course, the stored material still caused >80% mortality, 15 days after treatment. Comparative disease progression ratings also showed a similar trend. Overall results show that freeze-drying MV is a useful method to reduce the bulk and cumbersomeness of storing heavy liquid fermentation product, while retaining bioherbicidal activity. These findings increase the utility of this bioherbicide and offer the potential to use the dried material in soil treatments or in a more concentrated form than attainable via the fermented product.展开更多
BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative t...BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.展开更多
Objective： To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection （SSLA） in treating coronary heart diseases angina pectoris （CHD-AP） of Xin-blood stasis syn...Objective： To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection （SSLA） in treating coronary heart diseases angina pectoris （CHD-AP） of Xin-blood stasis syndrome type, and to conduct the non-inferiority trial with Danshen injection （丹参注射液, DSI） as positive control. Methods： An non-inferiority clinical layered, segmented, randomized, and blinded trial on three parallel and multiple centered groups was conducted in 480 patients with stable effort angina grade Ⅰ , Ⅱand Ⅲ, who had two or more times of attack every week. The 240 patients in test group A were treated with SSLA 200 mg added in 250 ml of 5% glucose solution for intravenous dripping every day; the 120 patients in test group B were treated with SSLA but the dosage doubled; and the 120 patients in the control group were treated with DSI 20 ml daily in the same method as SSLA was given. The clinical effectiveness and safety were evaluated after the patients were treated for 14 days. Results： The results showed that the markedly effective rate in test groups A, B and control group was 37.45 %, 36.75 % and 30.09 % respectively, while the total effective rate in them was 88.09%, 89.74% and 67.26% respectively. Statistical significance was shown in comparisons of the therapeutic effect between control group with test group A and test group B, with that in the two test groups superior to that in the control group, and non-inferiority trial showed eligibility （P〈0.01）. Adverse reaction appeared in 8 patients in the test groups and 2 in the control group. Conclusion： SSLA has definite therapeutic effect in treating patients with CHD-AP, with its effect not inferior to that of DSI, and no evident toxic-adverse reaction.展开更多
Highly attenuated modified vaccinia Ankara（MVA） is sensitive to repeat freeze-thaw cycle and easy to lose activity. In order to make the activity of MVA vaccine remain stable during its manufacturing, storage, and a...Highly attenuated modified vaccinia Ankara（MVA） is sensitive to repeat freeze-thaw cycle and easy to lose activity. In order to make the activity of MVA vaccine remain stable during its manufacturing, storage, and administration, the lyophilization as a good option could be resorted to; through screening, the right stabilizer composition and its production procedure were obtained. The final moisture content of freezing-dried recombinant MVA-HIV vaccine was lower than 3%. It can be reconstituted quickly and shows regular physical appearance and stable potency. In vivo functional experiment, mice were divided randomly into the liquid vaccination group, the lyophilized vaccination group, and the control group. Having been DNA vaccine priming, the mice were boosted with a dose of 10^7 pfu MVA- HIV vaccine, which produced indistinguishable antibody titer and cytotoxic T-lymphocyte（CTL） level compared with those of liquid vaccination group （ P 〉 0.05 ）. These results demonstrate that lyophilized MVA vaccine can induce high immunogenicity in mice.展开更多
Many researchers have employed the cryopreserved amniotic membrane（CAM） and corneal epithelial cells in the treatment of a severely damaged burned cornea, with corneal epithelial cells cultured on an amniotic membra...Many researchers have employed the cryopreserved amniotic membrane（CAM） and corneal epithelial cells in the treatment of a severely damaged burned cornea, with corneal epithelial cells cultured on an amniotic membrane （AM）. The lyophilized amniotic membrane（LAM） has a higher graft take and a longer shelf life; it is easier to store and safer because of gamma irradiation. Two Teflon rings（ Ahn＇s supporter） were made for culturing the cells on the LAM, and were then used to support the LAM. To reconstruct a corneal layer composed of corneal fibroblasts and epithelium, the corneal fibroblasts were first cultivated on the stromal side of LAM for five days, foUowed by epithelial cells culture on the epithelial side, by using the air-liquid interface culture. The reconstructed corneal layer composed of corneal fibroblasts and corneal epithelial cells has a much healthier basal layer of corneal epithelium than the reconstructed corneal epithelium, which was got by using only corneal epithelial cells, and resembles the epithelium of normal corneas, without the horny layer. Thus, the reconstruction of the corneal layer by using a LAM is considered to be a good in vitro model, not only for its application in toxicological test kits, but also for transplantation in patients with a severely damaged cornea.展开更多
Fibronectin has a good repair effect on skin,but its practical application is limited by its easy degradation and difficult preservation.Freeze-drying technology can extend the shelf life of biological products,but ma...Fibronectin has a good repair effect on skin,but its practical application is limited by its easy degradation and difficult preservation.Freeze-drying technology can extend the shelf life of biological products,but may cause damage to some of their biological activities.Therefore,it is necessary to conduct comprehensive and scientific testing of fibronectin lyophilized powder prepared by freeze-drying technology to evaluate its actual efficacy.In this study,by means of in vitro cell experiment,zebrafish animal model experiment and the experiment on the human skin,the safety of fibronectin lyophilized powder prepared by the new formula and the actual efficacy of skin repair were preliminarily and multidimensionally evaluated,so as to provide reference and basis for further research,human clinical trial and application.The results showed that fibronectin lyophilized powder prepared by the new formula had low cytotoxicity,significant ability of promoting cell migration and proliferation,and had stronger skin repair effect.The new Fibronectin lyophilized powder has the characteristics of good safety and strong skin repair effect,which shows that it has good development prospects.These results provide a new strategy for the development of skin repair products.展开更多
Lipid nanoparticles(LNPs)are critical for the delivery of drugs and nucleic acids.However,current mRNA-LNP formulations require stringent freezing for storage,which limits their global distribution.Our previous studie...Lipid nanoparticles(LNPs)are critical for the delivery of drugs and nucleic acids.However,current mRNA-LNP formulations require stringent freezing for storage,which limits their global distribution.Our previous studies demonstrated that optimizing the lipid type or molar ratio of Comirnaty-type mRNA-LNPs could enhance their lyophilization stability,thus improving their long-term storage stability under mild conditions.This study aims to enhance the storage stability of Spikevax-type mRNA-LNPs by optimizing lipid compositions and utilizing lyophilization for storage at 4�C.Fifteen mRNA-LNP formulations were evaluated for their physicochemical properties and transfection efficiency(TE)in human embryonic kidney(HEK)-293T cells using the I-optimal design of mixture experiments.Mathematical models were developed to predict the relationships among encapsulation efficiency,transfection performance and lipid ratios.The optimized mRNA-LNP formulation(N4),with a 1,2-distearoyl-sn-glycero-3-phosphocholine(DSPC)-to-cholesterol ratio of 0.36,exhibited superior stability and TE after lyophilization.N4 outperformed the original Spikevax formulation in several cell lines,including eye-derived ARPE-19 cells and lung-derived A549 cells.In vivo,N4 demonstrated high TE in the spleen of C57BL/6 mice both before and after lyophilization,with no signals observed in the kidneys,heart or eyes.These findings suggest that the optimized N4 formulation offers a robust,stable and efficient delivery system for gene therapy and vaccines,potentially overcoming the storage limitations of current Spikevax-type mRNA-LNPs and broadening their therapeutic applications.展开更多
Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying m...Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.展开更多
基金Youth Science Foundation Project of Sichuan Provincial Department of Science and Technology(2022NSFSC1437)Special Project of Scientific and Technological Research of Sichuan Provincial Administration of Traditional Chinese Medicine(2021MS121)Fundamental Research Funds for the Central Universities of Southwest Minzu University(ZYN2022040).
文摘[Objectives]To enhance the skin permeability of hydroxypropyl tetrahydropyrantriol and provide a reference for the subsequent prevention or treatment of skin aging.[Methods]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was investigated using a single factor method,and a quality evaluation system was established based on the appearance,particle size,PDI,and re-dispersibility of the lyophilized samples.[Results]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was determined by single factor experiments.The pre-freezing period was 16 h at-80℃,the total drying time was 36 h,and the addition of 10%mannitol-sucrose was used as the lyoprotectant.[Conclusions]The product prepared by the lyophilization method exhibits a fluffy and full appearance,with minimal shrinkage and collapse.The volume remains consistent before and after lyophilization,and the re-dispersibility is satisfactory.The re-dissolution process is rapid,and the particle size and polydispersity index(PDI)remain largely unchanged before and after lyophilization.
基金supported by the National Natural Science Foundation of China[grant number 51876185]archaeological artifact protection technology project of Zhejiang Province grant number 2017008].
文摘Pre-freezing is an important stage in freeze-drying processes.For the lyophilization of a cell,freezing not only plays a role for primary dehydration,but it also determines the amount of residual(intracellular or extracellular)water,which in turn can influence the solution properties and the choice of operation parameters.The freezing of human platelets in lyoprotectant solution is theoretically investigated here.A two-parameter model and an Arrhenius expression are used to describe cell membrane permeability and its temperature dependency.It is assumed that the intracellular solution is composed of four components:sodium chloride,trehalose,serum protein and water,while the extracellular solution consists of three components.Non-ideal solution behaviors are predicted using measured data.The concentration of maximally freeze-concentrated solution is estimated on the basis of an assumption of solute hydration.The impacts of lyoprotectant composition and extracellular sub-cooling on intracellular supercooling and residual water content in the cell are analyzed.The values of activation energy of hydraulic permeability at low temperatures are tested to study their impact on the critical cooling rate.As the mass fraction extracellular lyoprotectant(trehalose+bovineserum albumin)increases from 5 wt%to 20 wt%,the intracellular water content at the end of freezing does not change,but the intracellular solution undergoes much higher super-cooling degree.Increasing the mass ratio of trehalose to bovine serum albumin does not change the intracellular water content,but can mitigate intracellular super-cooling.While 0.05 mol/kg trehalose is loaded into platelet,the total quantity of residual water at the end of freezing may raise by 4.93%.The inclusion of dimethyl sulfoxide(Me2SO)in protectant may bring negative impacts to the drying stage by increasing the residual water content and lowering the drying temperature.
文摘Freeze-drying or lyophilization is a multi-stage operation of effectively drying a material while preserving its biological properties.The material is subject to being frozen and sublimated under vacuum upon heating.Lyophillized products are more stable,easily transported and quickly reconstituted.A benefit of low-temperature operation envisages its applications in pharmaceuticals for heat-sensitive components including vaccine and biological products.To date,analyses of the freeze-drying process have been changed from physical aspects of freezing and sublimation to a more sophisticated examination of the effects of the process on the chemical structures and the biological properties of the products themselves[1].
文摘Nifedipine-solid-lipid nanoparticles lyophilized with trehalose (NI-SLN-Tre) were prepared by the high pressure homogenization of a roll mixture consisting of NI and hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol, and in vivo pharmacokinetic properties and their hemocompatibility were determined and compared with those of a NI-SLN suspension. The resulting pharmacokinetic data demonstrated that although no significant differences were observed between the time of peak concentration (Tmax), peak plasma concentration (Cmax), and the area under the curve (AUC0→∞) values of both administrated samples, NI tended to be absorbed to a much greater extent from the lyophilized NI-SLN-Tre suspensions because of the enhanced solvation of NI-SLN in gastrointestinal fluid, derived from formation of hydrogen bonds between the polar head groups of the lipids and the O-H groups of trehalose. Furthermore, the results of a hemolysis assay revealed that the NI-SLN and NI-SLN-Tre suspensions showed good hemocompatibility properties with hemolysis values of less than 5%. Taken together, the results of this study demonstrate that NI-SLN-Tre exhibits suitable pharmacokinetic properties and good biocompatibility.
基金Supported by School-based Scientific Research Project of Hebi Polytechnic in 2022 (2022-KJZD-001).
文摘This paper reviewed the unique biological function of trehalose and its mechanism of stabilizing biological macromolecules and the research progress in the protective effect of trehalose on lactic acid bacteria fermentation starters during lyophilization in food production.The application of trehalose in food industry was prospected.
文摘Objectives: To improve the aqueous solubility and dissolution of fexofenadine HCl, an attempt was made to prepare its fast dissolving tablets by lyophilization technique. Methods: For the preparation of lyophilized tablets (F1-F32), the drug was dispersed in a hydrated solution of water-soluble polymers (gelatin/maltodextrin/acacia) containing glycine and mannitol. The blend was pelted down into the patches of a blister pack, frozen down and then lyophilized. Different characterization parameters viz. differential scanning calorimetry, hardness, weight variation, X-ray diffraction (XRD), scanning electron microscopy (SEM), mercury porosimetry, solubility, wetting time and water absorption ratio, lyophilization tablet index, drug content, in vitro dissolution and stability were evaluated. Key findings: Tablets (F32) containing acacia were found to have fast disintegration and relatively higher mechanical strength with improved drug solubility. X-ray diffractogram and scanning electron micrograph indicated decrease in crystallinity of drug and a good porous structure property for prepared tablet, respectively. Dissolution study showed complete drug released within 5 min. Moreover, tablets (F32) were found to be stable for one month at 25 ± 2 °C/60 ± 5% relative humidity.
文摘The aim of present study was to use QbD approaches to evaluate the effect of independent product variables and their interaction on particle size of sodium fluoride and then obtain the optimized experimental condition for predefined particle size of sodium fluoride. The sodium fluoride is mainly used in dental preparation for delivering the fluoride ion to the tooth enamel for that nano-particle size is required. Nowadays the milling process is used to reduce the particle size. But that process has some limitations due to crystalline nature of sodium fluoride;for overcoming those limitations, lyophilization method is used. A 4<sup>3</sup> level full factorial design was used to study the significant influence of process and product variables i.e. 1) Concentration of sodium fluoride, 2) Concentration of PVP, 3) Sample volume, 4) Drying surface, on particle size of sodium fluoride. The experimental design result shows that independent product variables significantly modify the structure and improve particle size reduction of sodium fluoride.
基金supported by a National Research Foundation of Korea Grant,funded by the Korean government(MEST)(NRF-2021R1A2C3011051)Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2022M3A9I5018286).
文摘In the probiotics manufacturing process,lyophilization damages the cell membrane of microorganisms,reducing their viability and delaying reactivation of their cellular metabolism.The growth phase of microorganisms at the time of lyophilization is thought to significantly affect their viability during storage and reactivation in the intestine.However,no study has systematically investigated the differences in overcoming mechanisms in microorganisms harvested at different growth phases against lyophilization.Therefore,in this study,we comparatively assessed the resistance mechanism of Bifidobacterium animalis ssp.lactis and Lacticaseibacillus rhamnosus harvested at exponential and stationary growth phases.We found that B.animalis ssp.lactis and L.rhamnosus harvested at the stationary phase had shorter lag phase in growth and higher survival rates during storage than those harvested at the exponential phase.As a result of metabolome analysis,the cells harvested at the stationary phase accumulated trehalose and arabinose,which function as cryoprotectants and protect cells from lyophilization-induced damage.These findings could provide a basis for establishing a manufacturing protocol for lyophilized probiotics that can be rapidly reactivated in the intestine to achieve optimal metabolic activity and induce health benefits.
基金supported by Science and Technology Planning Project of Guangdong Province,China(No.2014A020213007)
文摘Objective To observe changes on membrane integrity and ultrastructure of human sperm after freeze-drying.Methods Semen samples from both normospermic donors（group A, n=15） and infertile men with abnormal sperm parameters（group B, n=15） were enrolled into this study. These samples were freeze-dried by using a freeze-drying method. The membrane integrity in the head and tail regions of individual spermatozoon was examined by using the combined hypo-osmotic swelling-eosin Y exclusion test. Sperm ultrastructure in groups A（n=3） and B（n=3） was observed by scanning electron microscopy（SEM）.Results After freeze-drying, all spermatozoa were types I（damaged both head and tail membranes） and III（damaged head membrane and intact tail membrane） membrane integrity in groups A and B. Type III of group B had lower value than that of group A（P〈0.01）. Under SEM, intact freeze-dried spermatozoa including abnormal morphology and normal-looking morphology were observed in both groups A and B. A few freezedried sperm heads had unsmooth or fuzzy surface. Isolated sperm heads, bent tails,broken sperm tails or fragmentary tails were more frequently seen in group B than those in group A.Conclusion Freeze-dried human spermatozoa could have intact structural components. However, freeze-drying resulted in severe damage on membrane integrity and ultrastructure of sperm. Samples from infertile men would have less resistance to freeze-drying.
文摘Hybrid aerogels have been prepared by freeze-drying technique after mixing water dispersions of cellulose microfibers or cellulose nanofibers and silica(SiO2)of type SBA-15(2D-hexagonal).The prepared composites were characterized by different analysis techniques such as SEM,hot-filament,DMA,etc.These composites are compared to those previously prepared using nanozeolites(NZs)as mineral charge.The morphology studied by SEM indicated that both systems have different structures,i.e.,individual fibers for cellulose microfibers WP-based aerogels and films for nanofibrillated cellulose NFC-based ones....These differences seem to be driven by the charge of the particles,their aspect ratio and concentrations.These hybrid materials exhibit tunable thermal conductivity and mechanical properties.The thermal conductivity values range between^18 to 28 mW.m^-1.K^-1 and confirm the superinsulation ability of these fibrous aerogels.Synergism on the thermal insulation properties and mechanical properties was shown by adjunction of mineral particles to both cellulose-based aerogels by reaching pore size lower than 100 nm.It significantly reduces the thermal conductivity of the hybrid aerogels as predicted by Knudsen et al.Furthermore,the addition of mineral fillers to aerogels based on cellulose microfibers induced a significant increase in stiffness.
文摘The main objective of the present work is to design aspirin nanoparticles loaded suppositories which will reduce the side effects caused by aspirin suppositories. Aspirin nanoparticles were prepared initially based on ionic-gelation mechanism and lyophilized. The prepared nanoparticles were evaluated, and the results confirmed that Fa9 formulation was the best with greater drug entrapment efficiency. Aspirin suppositories were prepared in order to investigate the best base composition. The prepared suppositories were evaluated and FS1, FS3, FS4, FSS, FS1 l, and FS12 were proved to be the best base compositions based on dissolution performed. The lyophilized aspirin nanoparticles of Fa9 were used to prepare aspirin nanoparticles loaded suppositories. The in vitro results revealed that Fasl 1 was the best formulation.
基金Funded by the National Natural Science Foundation of China(No.11447215)Scientific Research Project of Mianyang Normal University(No.2013A02)Research Fund of Education Department of Sichuan Province(No.13ZB0118)
文摘Poly（Imino Ketone） （PIK） is a group of novel high performance polymer material with excellent thermal properties and dissolubility. Aiming at the requirements of inertial confined fusion （ICF） studies on low density polymer foams, we firstly synthesized poly（imino imino ketone） （PIIK） by palladium catalyzed C-N cross-coupling reaction, and successfully prepared the PIIK foam material with a density of 80-300 mg/cm3 by using PIIK as the raw material with thermal-induced phase separation and lyophilization technique. Mercury injection method was used to determine the structure of PIIK foams, and the results indicated that the mean pore diameter was lower than 5 ~tm and it had relatively high voidage and specific surface area.
文摘The shelf-life of a bioherbicide product is an important factor with regard to its commercial potential. The bioherbicidal efficacy of freshly fermented Myrothecium verrucaria (strain IMI 368023) (MV) mycelia formulations and MV mycelia preparations that had been freeze-dried and then stored at -20°C for 8 years was compared. Two concentrations of each formulation (1.0x and 0.5x) were tested, utilizing bioassays on seedlings of the weed, hemp sesbania (Sesbania exaltata) under greenhouse conditions or in darkness utilizing hydroponically grown seedlings. Freeze drying of freshly prepared MV mycelium produced a light, brownish-colored powder. Efficacy tests of this reconstituted 8-year-old dried material showed that some bioherbicidal activity was lost during long-term storage, i.e., ~20% and ~60% seedling dry weight reduction at the 1.0x and 0.5x rate, respectively. Although plant mortality was greater in the fresh mycelial preparations treatments versus the freeze-dried and stored samples at all time points in the time-course, the stored material still caused >80% mortality, 15 days after treatment. Comparative disease progression ratings also showed a similar trend. Overall results show that freeze-drying MV is a useful method to reduce the bulk and cumbersomeness of storing heavy liquid fermentation product, while retaining bioherbicidal activity. These findings increase the utility of this bioherbicide and offer the potential to use the dried material in soil treatments or in a more concentrated form than attainable via the fermented product.
文摘BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.
基金Supported by the Fund of National Project of High.technicResearch and Development,(No.2003AA223269)
文摘Objective： To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection （SSLA） in treating coronary heart diseases angina pectoris （CHD-AP） of Xin-blood stasis syndrome type, and to conduct the non-inferiority trial with Danshen injection （丹参注射液, DSI） as positive control. Methods： An non-inferiority clinical layered, segmented, randomized, and blinded trial on three parallel and multiple centered groups was conducted in 480 patients with stable effort angina grade Ⅰ , Ⅱand Ⅲ, who had two or more times of attack every week. The 240 patients in test group A were treated with SSLA 200 mg added in 250 ml of 5% glucose solution for intravenous dripping every day; the 120 patients in test group B were treated with SSLA but the dosage doubled; and the 120 patients in the control group were treated with DSI 20 ml daily in the same method as SSLA was given. The clinical effectiveness and safety were evaluated after the patients were treated for 14 days. Results： The results showed that the markedly effective rate in test groups A, B and control group was 37.45 %, 36.75 % and 30.09 % respectively, while the total effective rate in them was 88.09%, 89.74% and 67.26% respectively. Statistical significance was shown in comparisons of the therapeutic effect between control group with test group A and test group B, with that in the two test groups superior to that in the control group, and non-inferiority trial showed eligibility （P〈0.01）. Adverse reaction appeared in 8 patients in the test groups and 2 in the control group. Conclusion： SSLA has definite therapeutic effect in treating patients with CHD-AP, with its effect not inferior to that of DSI, and no evident toxic-adverse reaction.
基金Supported by the National Natural Science Foundation of China(No30371317)
文摘Highly attenuated modified vaccinia Ankara（MVA） is sensitive to repeat freeze-thaw cycle and easy to lose activity. In order to make the activity of MVA vaccine remain stable during its manufacturing, storage, and administration, the lyophilization as a good option could be resorted to; through screening, the right stabilizer composition and its production procedure were obtained. The final moisture content of freezing-dried recombinant MVA-HIV vaccine was lower than 3%. It can be reconstituted quickly and shows regular physical appearance and stable potency. In vivo functional experiment, mice were divided randomly into the liquid vaccination group, the lyophilized vaccination group, and the control group. Having been DNA vaccine priming, the mice were boosted with a dose of 10^7 pfu MVA- HIV vaccine, which produced indistinguishable antibody titer and cytotoxic T-lymphocyte（CTL） level compared with those of liquid vaccination group （ P 〉 0.05 ）. These results demonstrate that lyophilized MVA vaccine can induce high immunogenicity in mice.
文摘Many researchers have employed the cryopreserved amniotic membrane（CAM） and corneal epithelial cells in the treatment of a severely damaged burned cornea, with corneal epithelial cells cultured on an amniotic membrane （AM）. The lyophilized amniotic membrane（LAM） has a higher graft take and a longer shelf life; it is easier to store and safer because of gamma irradiation. Two Teflon rings（ Ahn＇s supporter） were made for culturing the cells on the LAM, and were then used to support the LAM. To reconstruct a corneal layer composed of corneal fibroblasts and epithelium, the corneal fibroblasts were first cultivated on the stromal side of LAM for five days, foUowed by epithelial cells culture on the epithelial side, by using the air-liquid interface culture. The reconstructed corneal layer composed of corneal fibroblasts and corneal epithelial cells has a much healthier basal layer of corneal epithelium than the reconstructed corneal epithelium, which was got by using only corneal epithelial cells, and resembles the epithelium of normal corneas, without the horny layer. Thus, the reconstruction of the corneal layer by using a LAM is considered to be a good in vitro model, not only for its application in toxicological test kits, but also for transplantation in patients with a severely damaged cornea.
文摘Fibronectin has a good repair effect on skin,but its practical application is limited by its easy degradation and difficult preservation.Freeze-drying technology can extend the shelf life of biological products,but may cause damage to some of their biological activities.Therefore,it is necessary to conduct comprehensive and scientific testing of fibronectin lyophilized powder prepared by freeze-drying technology to evaluate its actual efficacy.In this study,by means of in vitro cell experiment,zebrafish animal model experiment and the experiment on the human skin,the safety of fibronectin lyophilized powder prepared by the new formula and the actual efficacy of skin repair were preliminarily and multidimensionally evaluated,so as to provide reference and basis for further research,human clinical trial and application.The results showed that fibronectin lyophilized powder prepared by the new formula had low cytotoxicity,significant ability of promoting cell migration and proliferation,and had stronger skin repair effect.The new Fibronectin lyophilized powder has the characteristics of good safety and strong skin repair effect,which shows that it has good development prospects.These results provide a new strategy for the development of skin repair products.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LQ24H120006)the Wenzhou Municipal Science and Technology Bureau(Y2023799)+3 种基金the Startup Foundation for Scientific Research,Eye Hospital,Wenzhou Medical University(KYQD20211204)the National Natural Science Foundation of China(52250710155)the National Key Research and Development Program of China(2021YFA1101200,2022YFA1105501)the Project of State Key Laboratory of Ophthalmology,Optometry and Visual Science,the Wenzhou Medical University(J02-20210201).
文摘Lipid nanoparticles(LNPs)are critical for the delivery of drugs and nucleic acids.However,current mRNA-LNP formulations require stringent freezing for storage,which limits their global distribution.Our previous studies demonstrated that optimizing the lipid type or molar ratio of Comirnaty-type mRNA-LNPs could enhance their lyophilization stability,thus improving their long-term storage stability under mild conditions.This study aims to enhance the storage stability of Spikevax-type mRNA-LNPs by optimizing lipid compositions and utilizing lyophilization for storage at 4�C.Fifteen mRNA-LNP formulations were evaluated for their physicochemical properties and transfection efficiency(TE)in human embryonic kidney(HEK)-293T cells using the I-optimal design of mixture experiments.Mathematical models were developed to predict the relationships among encapsulation efficiency,transfection performance and lipid ratios.The optimized mRNA-LNP formulation(N4),with a 1,2-distearoyl-sn-glycero-3-phosphocholine(DSPC)-to-cholesterol ratio of 0.36,exhibited superior stability and TE after lyophilization.N4 outperformed the original Spikevax formulation in several cell lines,including eye-derived ARPE-19 cells and lung-derived A549 cells.In vivo,N4 demonstrated high TE in the spleen of C57BL/6 mice both before and after lyophilization,with no signals observed in the kidneys,heart or eyes.These findings suggest that the optimized N4 formulation offers a robust,stable and efficient delivery system for gene therapy and vaccines,potentially overcoming the storage limitations of current Spikevax-type mRNA-LNPs and broadening their therapeutic applications.
基金supported by the National Key Research and Development Program of China(No.2017YFC1700400,2017YFC1700405)the National Natural Science Foundation of China(No.81921001,82122073)。
文摘Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.
