301 results about "Drug loading dose" patented technology

Disclosed is an oral apparatus for injection administration in the digestive tract, comprising a housing, a trigger assembly, and an administration assembly. The housing comprises a top cover at the upper part thereof, a middle housing placed in the middle, and a base located at the bottom. The material density of the middle housing is less than the material density of the base, so that the apparatus is in the shape of a roly-poly toy. The trigger assembly comprises a soluble fixing member, an elastic member, and a transmission member. The administration assembly comprises a microneedle and a drug. The apparatus provided by the present invention, by means of an arranged liquid storage bag, greatly increases the drug loading capacity and can theoretically achieve a drug loading capacity of 50 mg, which is a significant improvement over the prior art.

The invention provides a sustained-release microneedle for treating ill-conditioned pregnancy and a preparation method and application thereof, and relates to the technical field of biological medicines.The sustained-release microneedle for treating ill-conditioned pregnancy comprises a base and a needle tip on the base, the needle tip part of the gel microneedle is made of heparin medicine, and the needle tip part of the gel microneedle is made of gelatin. The heparin medicine comprises heparin, heparin sodium, low-molecular heparin, low-molecular heparin sodium or low-molecular heparin calcium; the needle point part comprises a heparin photo-crosslinking monomer, and the base comprises a biocompatible polymer matrix. The sustained-release microneedle for treating pathological pregnancy provided by the embodiment of the invention has good mechanical strength, skin permeability and anticoagulant activity, can reduce skin bruises caused by subcutaneous injection of heparin, improves abortion caused by infection and inflammation and abortion caused by APS (anti-phospholipid antibody syndrome), can realize sustained release of drugs and increase of drug loading capacity, and has good application prospects. Sustainable drug delivery is achieved, and frequent injection is avoided.

The invention is applicable to the technical field of biomedicine, and provides dipeptide-photosensitizer molecule co-assembled nanoparticles as well as a preparation method and application thereof. According to the invention, cationic diphenylalanine (CDP) and a biological cross-linking agent genipin are self-assembled to form a dipeptide carrier, and then the dipeptide carrier and a photosensitizer molecule chlorin e6 (Ce6) are co-assembled, so that nanoparticles with controllable size, controllable drug loading capacity and good biocompatibility are successfully prepared. The preparation method is simple and easy to implement, effectively solves the key problems that the traditional photosensitizer molecule Ce6 is poor in biocompatibility and easy to gather, not only can efficiently deliver Ce6, but also obviously improves the application safety and biocompatibility of Ce6. The Ce6 is almost free of dark toxicity under a dark condition, can play a strong photodynamic killing role under illumination, and greatly improves the possibility and application potential of the Ce6 in tumor photodynamic therapy by virtue of the flexible regulation and control advantages of the size and the drug loading capacity.

The invention discloses a colchicine external preparation with high intradermal residual quantity and percutaneous transmittance as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. The invention provides a colchicine external preparation with high intradermal residue and transdermal transmittance. The colchicine external preparation comprises: a) colchicine or a pharmaceutically acceptable salt thereof; b) a penetration enhancer; c) pharmaceutically acceptable excipients and / or excipients; the penetration enhancer is at least one of polyglycerol oleate or isosorbide dimethyl ether. The drug loading capacity and the percutaneous transmittance of the colchicine external preparation disclosed by the invention are remarkably improved. When polyglycerol oleate is selected as a penetration enhancer to prepare colchicine gel, the intradermal retention volume can reach 358.08 micrograms within 20 hours. When isosorbide monomethyl ether is selected as a penetration enhancer to prepare ethosome gel, the accumulated penetration amount can reach 106.87 mu g / cm < 2 >, and the intradermal residual amount can reach 90.58 mu g or above.

The invention relates to an application of a CAR exosome drug carrier in tumor treatment. The application of the CAR exosome loaded medicine in tumor treatment is based on the strategy of CAR exosome coupling medicine, so that the completeness of the exosome and the controllability of the medicine loading capacity are greatly protected, the purpose of accurately delivering the medicine to tumors in a targeted manner is achieved, and a new direction is provided for tumor treatment.

The invention discloses folate receptor mediated manganese ion coordination type cabazitaxel-loaded albumin nanoparticles as well as a preparation method and application thereof. Human serum albumin is covalently linked with folic acid through an amide condensation reaction to obtain a folic acid-albumin modifier with folic acid targeting; further combining with manganese ions through metal coordination to form a folic acid-albumin-manganese ion modifier with a targeting function; finally, efficient loading of cabazitaxel is achieved through a simple heating polymerization method, and the folate receptor mediated cabazitaxel-loaded albumin nanoparticles are formed. According to the nanoparticles provided by the invention, the particle size is about 140 nm, the stability is good, and the drug loading capacity and the encapsulation efficiency of cabazitaxel are high; the compound has a slow release effect, is good in in-vitro release behavior, and has important application value in the aspect of targeted delivery of drugs to tumors. Compared with other traditional nanoparticles, the nanoparticles show a remarkable anti-tumor effect.

This invention discloses a protein-polysaccharide ternary nanoparticle loaded with cordycepin, its preparation method, and its applications. The invention employs a layer-by-layer self-assembly method to modify the surface of zein nanoparticles. Since zein has a positive surface charge, the first layer modification uses the anionic polysaccharide sodium alginate for electrostatic bonding, and the second layer modification uses the cationic polysaccharide chitosan, constructing positively charged ternary composite nanoparticles. These nanoparticles have small particle size, high encapsulation efficiency, high drug loading capacity, and a sustained-release effect, significantly reducing cytotoxicity and significantly improving the therapeutic effect on osteoarthritis. This invention develops a novel cordycepin formulation, overcoming the limitations of cordycepin's clinical use.

The invention relates to the technical field of burn and scald treatment, in particular to an intelligent hydrogel dressing for targeted regulation and control of Mongolian medicine release. The dressing comprises a core-shell microsphere drug loading system used for realizing physical segmentation of a functional area; the dual-release system is used for realizing surface adsorption of quick-release drug nanoparticles and internal wrapping of sustained-release microspheres; a hydrogel matrix for forming a nanofiber network; and the magnetic control regulator is magnetic nanoparticles dispersed in the hydrogel matrix, and regulates the aperture of the hydrogel network through the action of an external magnetic field. According to the intelligent hydrogel dressing for targeted regulation and control of Mongolian medicine release, the Mongolian medicine compound intelligent hydrogel dressing is developed on the basis of a TRIZ innovative method; through a core-shell microsphere drug loading system and a dual release design, high drug loading capacity and accurate drug release control are synchronously realized.

The invention belongs to the field of polymer chemistry and biological medicine materials, and relates to application of a polymer polysaccharide slow-release carrier in medicinal and edible components and a preparation method of the polymer polysaccharide slow-release carrier. The carrier is composed of phytic acid-genipin cross-linked modified chitosan, tannic acid, sodium lactate, glycerin, vitamin E acetate, sodium alginate and deionized water. The phytic acid-genipin cross-linked modified chitosan is prepared by reacting chitosan with phytic acid and genipin, and has reversible cross-linking and polydentate coordination properties; the tannic acid and the modified chitosan can form a multi-point hydrogen bond and esterification network. The carrier is prepared through sol-gel forming or spray drying, is stable in structure, good in dispersity, high in drug loading capacity, stable in an acid environment and controllable in release under a neutral condition, remarkably improves the slow release performance and bioavailability of medicinal and edible components, and is suitable for functional food and drug delivery systems.

The invention relates to the technical field of pharmaceutical preparations, in particular to a pure drug-based nano preparation constructed by super-solubilization of a natural polyphenol material and a biguanide drug and a preparation method of the pure drug-based nano preparation. The pure drug-based nano preparation constructed by super solubilization of the natural polyphenol material and the biguanide drug provided by the invention is composed of the natural polyphenol material and the biguanide drug, and a phenolic hydroxyl group of the natural polyphenol material and an amino group of the biguanide drug are self-assembled into the nano preparation through electrostatic interaction and hydrophilic and hydrophobic effects, namely the pure drug-based nano preparation. The mass ratio of the natural polyphenol material to the biguanide drug is 1: (0.0001-10000). The pure drug-based nano preparation provided by the invention has the advantages of high drug loading capacity, simple preparation process, greenness, high efficiency, safety and suitability for industrial application.

The invention discloses a gelatin-silk fibroin composite drug-loaded nanoparticle, which is characterized in that gelatin and silk fibroin are co-assembled through physical crosslinking to form a stable composite structure, the silk fibroin forms a physical crosslinking network through a beta-folding structure, and the gelatin is distributed in the network. The invention further discloses a preparation method of the nano-particles and application of the nano-particles in preparation of drugs for treating inflammatory diseases. The nanoparticle does not need a chemical cross-linking agent, has the characteristics of controllable particle size, high drug loading capacity, high encapsulation efficiency and MMP-9 enzyme response drug release, has good biocompatibility and anti-inflammatory effect, and can be used for treating inflammatory diseases.

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a cromolyn sodium eye drop without antioxidant. The cromolyn sodium eye drop comprises cromolyn sodium liposome and pharmaceutically acceptable additives; a formula is preferred in the preparation process of the cromolyn sodium liposome, so that the cromolyn sodium liposome has a high drug loading and encapsulation efficiency, and lays a foundation for further preparation into a preparation. In addition, the cromolyn sodium liposome eye drop of the application does not add antioxidant, and also has high stability, and is qualified in a sterile test and has high light stability.

The invention discloses a curcumin nanocrystal preparation as well as a preparation method and application thereof. The invention relates to a curcumin nanocrystal composition which is prepared by drying and curing a curcumin nanocrystal suspension to a blank pellet core, the curcumin nanocrystal suspension contains 20-35% of curcumin nanocrystals, 1-10% of a three-dimensional protective agent and 1-10% of a charge protective agent, and the average particle size of the curcumin nanocrystals is 200-320 nm. The curcumin nanocrystal composition prepared by the invention can effectively prevent and treat heat stroke and complications thereof, remarkably improve heat tolerance, prolong survival time, reduce the level of inflammatory factors in blood, protect intestinal epithelial cells and intestinal barrier functions, reduce damage caused by heat stroke, prevent and treat body and organ damage caused by heat stroke, and improve the curative effect of the curcumin nanocrystal composition. The preparation has the advantages of being high in drug loading capacity, good in stability, high in bioavailability, safe, effective, convenient to carry and the like.

A pyridine amide compound-containing composition and a pharmaceutical composition, a preparation method therefor and a use thereof. The composition comprises an active ingredient and at least one matrix material, wherein the active ingredient is a compound represented by formula I or a pharmaceutically acceptable salt, a stereoisomer, a solvate, an isotopically labeled compound, a polymorph, a metabolite or a prodrug thereof. The composition has a high drug loading capacity, improves drug solubility, and has good stability. The in vivo bioavailability of the composition can reach the same level of bioavailability as that of a clear drug solution.

This invention discloses a GLP-1 peptide drug microneedle and its preparation method. The microneedle is composed of PVP, NVP, a photoinitiator, and a GLP-1 receptor agonist. The preparation method includes two steps: material preparation and peptide microneedle patch preparation. First, a certain amount of PVP is dissolved in NVP to prepare a solution with appropriate specific gravity and viscosity. Then, the photoinitiator and GLP-1 receptor agonist are added to the solution to form a liquid system that is as uniformly suspended as possible. Second, the suspension is filled into a microneedle mold, and NVP is polymerized into solid PVP by ultraviolet light irradiation. Under the constraint of the mold, the solid PVP forms the geometric shape of the microneedle. Subsequently, a small amount of NVP is spread evenly on the backing layer of the microneedle and covered with a plastic film. Ultraviolet light irradiation is applied again to crosslink the plastic film with the PVP microneedle, and the microneedle is then peeled out of the mold. The advantage of this application is that it uses PVP to prepare an NVP solution with suitable specific gravity and viscosity, so that the subsequently added drug is uniformly suspended in the solution, thereby improving the uniformity of drug loading on microneedles and increasing the drug loading capacity, which is beneficial to improving the efficacy and consistency of drug efficacy.

Disclosed are an epinastine hydrochloride oral dissolving film composition, a preparation method therefor, and use thereof. The present invention provides an epinastine hydrochloride oral dissolving film composition comprising an active drug, a film-forming material, and a flavoring agent. The active drug is one or more of 3-amino-9,13-dihydro-1H-dibenzo[c,f]-imidazo[1,5-a]azepine hydrochloride, which is represented by formula I, and a solvate thereof. The epinastine hydrochloride oral dissolving film composition of the present invention has the advantages of a small thickness, rapid disintegration, stable properties, good mechanical properties, a pleasant taste, instant oral dissolution without the need for water, and quick oral absorption. Moreover, the composition is uniform in appearance and good in flexibility, and the process is simple; no sedimentation occurs in the process of preparing a film solution; the content uniformity meets the requirement, and the drug loading capacity is high.

The invention discloses a PH response type modified polydopamine nano preparation loaded with icariin and application of the PH response type modified polydopamine nano preparation in myocardial ischemia resistance, and belongs to the technical field of biological medicine. The nano preparation takes polydopamine (PDA) as a carrier core, the carrier core is modified by methoxy polyethylene glycol (mPEG) and then loaded with icariin (ICA), and the nano preparation is named as mPEG-PDA (at) ICANPs; the preparation process comprises the steps of synthesis of mPEG-OTs, synthesis of mPEG-EDA, synthesis of PDA, preparation of mPEG-PDANPs and preparation of mPEG-PDA (at) ICANPs, under the optimal condition, the particle size of the preparation is 179.6 + / -0.432 nm, PDI is 0.130 + / -0.004, the Zeta potential is 23.4 + / -0.436 mV, the stability is good after the preparation is stored in a dark place at 4 DEG C for 30 days, the ICA drug loading capacity is 14.6 + / -1.08%, the encapsulation efficiency is 64.37 + / -2.31%, and the drug cumulative release rate reaches 73.31 + / -1.64% (pH response drug release) in an environment with the pH value of 6.5 for 72 hours. An in-vitro H9c2 cell OGD model experiment proves that the preparation can remarkably improve the survival rate of ischemic myocardial cells, inhibit apoptosis and reduce LDH release, and the effect of the preparation is superior to that of free ICA. The invention provides an efficient targeting drug delivery system for resisting myocardial ischemia, and has important clinical application value.

The present application relates to the application of traditional Chinese medicine active ingredient composition and its preparation in synergistic anti-tumor of PD-1 inhibitor. The traditional Chinese medicine active ingredient composition is a composition of oxymatrine and astragaloside B. The combination of the two can improve the anti-tumor effect of PD-1 inhibitor. In addition, it can also be used in the form of preparation to realize in vivo drug delivery in cooperation with its pharmaceutically acceptable carrier. The carrier can be selected from iron-based MOF and liposome, etc. to realize the co-loading of oxymatrine and astragaloside B with different polarity and efficient drug delivery. The iron-based MOF carrier has the advantages of high drug loading capacity and Fe ion which can cooperate with astragaloside B to improve the activity of tumor infiltrating T cells. The ferromagnetism and platelet membrane modification can also precisely target tumor tissue. The preparation technology of liposome is mature, which is conducive to industrialized production and has broad prospects for clinical transformation. The combination of the two with PD-1 inhibitor can significantly improve the anti-tumor effect of PD-1 inhibitor.

Methods of administering an anti-arrhythmic, such as dofetilide, to a patient in an amount effective for treating a cardiovascular condition are described. The drug can be administered intravenously for at least one hour. A loading dose of 0.1 to 12 μg / kg bodyweight over a duration of up to 60 minutes can be administered and / or a maintenance dose of 0.1 to 10 μg / kg / hr can be administered intravenously over a duration of at least 1 hour, optionally alternatively or in addition wherein the amount of the loading dose and / or the IV maintenance dose is in the range of about ±50% of a maintenance dofetilide dose. The cardiovascular condition can include atrial fibrillation or flutter, ventricular tachycardia, hemodynamically stable or unstable ventricular tachycardia, paroxysmal atrial fibrillation, ventricular fibrillation, paroxysmal supraventricular tachycardia, heart failure, coronary artery disease, or pulmonary artery hypertension. A patient's QT interval and / or a creatinine clearance can be measured, and the effective amount can be selected based on either or both of the QT interval or the creatinine clearance measurements.

The application provides a zwitterionic polypeptide modified paclitaxel derivative, a prodrug nanocarrier micelle and a preparation method thereof, and belongs to the field of biological medicines. The preparation method comprises the following steps: mixing a zwitterionic polypeptide containing a sulfhydryl group with 2,2'-dithiodipyridine in a polar solvent, stirring and reacting, crystallizing, and obtaining a polypeptide derivative containing a disulfide bond; and then dissolving the polypeptide derivative and a sulfhydrylated paclitaxel (PTX-SH) in a polar solvent, adding glacial acetic acid to adjust the pH, stirring and reacting, and obtaining the paclitaxel derivative. The paclitaxel derivative is used for preparing a prodrug nanocarrier micelle by loading a hydrophobic anticancer drug, the prodrug nanocarrier micelle has a long blood circulation time in the body, a high drug loading capacity, small toxic side effects, excellent glutathione response and fast on-demand controlled release characteristics, and good tumor inhibition effect.

The invention discloses an improved loading method of a nano-drug carrier, which comprises the following steps: adding a carrier of recombinant human heavy-chain ferritin or a derivative thereof into a high-concentration urea solution, mixing and reacting to depolymerize a shell of the recombinant human heavy-chain ferritin; adding a medicine, mixing and incubating; and diluting a reaction solution obtained by incubation into a low-concentration urea solution by using a Tris buffer solution, reacting for 8-15 hours to re-polymerize the recombinant human heavy chain ferritin shell, and finally changing the solution by using a membrane bag with the molecular weight cutoff of 50 KD through the Tris buffer solution to obtain the loaded ferritin drug composite particles. According to the preparation method provided by the invention, the effect of obviously improving the protein recovery rate and the drug loading capacity is achieved by providing a preparation method of replacing liquid after dilution and then standing and optimizing the drug-mass ratio, the protein recovery rate can reach 100%, and the drug loading capacity can reach 186 mu g / mL.

This invention discloses a meglumine-luteolin complex, its preparation method, and its applications, belonging to the interdisciplinary field of microbiome and drug delivery. Using luteolin as the main material, this invention employs a dual inclusion technique with hydroxypropyl-β-cyclodextrin and meglumine to synergistically prepare a meglumine-luteolin complex with colon-targeted delivery capabilities. This invention significantly improves the delivery efficiency and drug loading of luteolin in the colon through the dual inclusion technique. The preparation process is simple, and it exhibits excellent hypoglycemic effects and colon-targeted release characteristics in the treatment of diabetes and its complications.

The application belongs to the technical field of pharmaceutical preparations, and specifically provides a kind of indobufen freeze-dried oral disintegrating tablet and a preparation method thereof.The freeze-dried oral disintegrating tablet contains indobufen and xanthan gum, and the freeze-dried oral disintegrating tablet can be obtained by freeze-drying technology after the above components are prepared into a suspension.The freeze-dried oral disintegrating tablet provided by the application has the technical characteristics of good properties, complete demolding, high drug loading, good content uniformity, rapid disintegration and rapid dissolution, and can meet the needs of rapid anti-platelet therapy in acute thrombosis events.

The invention involves a novel method of converting atrial fibrillation (AF) or atrial flutter (AFL) in a patient presenting with highly symptomatic AF or AFL by administering at least a loading dose of dofetilide intravenously, or if that fails cardioversion and a maintenance infusion followed by a switch to chronic oral dosing.

The present invention relates to a coating material for drug-coated balloons, drug-coated balloons, and a coating solution for drug-coated balloons, as well as their preparation and application. The coating solution comprises an aqueous solvent and a plurality of core-shell structures dispersed in the aqueous solvent, each of which comprises a lipid bilayer coated with a drug. The core of the core-shell structure contains a plurality of drug-loaded particles, and the shell of the core-shell structure is a lipid bilayer with an outer hydrophilic group and an inner hydrophobic group. The drug-loaded particles comprise a plurality of drug-loaded nanocrystalline particles. The combination of nanocrystals and liposomes combines the advantages of these two types of drug carriers. The resulting lipid bilayer improves the solubility of poorly soluble drugs in drug-coated balloons, resulting in a high drug loading capacity, high drug carrier stability, and stable drug crystal form, allowing for controllable drug release rates.

The application relates to the technical field of medical materials, in particular to a novel degradable metal drug loading method. 6 Pa to 3.0x10 7 Pa pressure conditions to press into an ellipsoidal metal block, then the metal block is secondarily pressed under the condition of 5-20 GPa pressure, then pressure is kept for 5-20 hours, finally the pressure is released to normal pressure, and the target drug-loaded metal sample is obtained. The novel degradable metal drug loading method uniformly loads and slowly releases drugs in the degradable metal through a pure physical method for the first time, and solves the problems of small drug loading dose, short release time, drug burst release and the need to introduce a drug carrier in the traditional drug loading method.

The application discloses a low-oxygen and pH dual-response nano-carrier, a drug-loaded nanoparticle and application thereof, and belongs to the technical field of biological medicines. The nano-carrier with moderate particle size and low-oxygen and pH dual-response is obtained by using the reaction of aldehyde benzoic acid, nonaethylene glycol and azo-p-phenetidine, the nano-carrier is specifically targeted to a tumor site, and then specifically releases drugs, thereby reducing toxic side effects; meanwhile, after the nano-carrier responds, benzaldehyde groups are released, the benzaldehyde groups are covalently connected with proteins on a lysosome membrane, the structure and activity of the proteins are changed, the lysosome membrane is broken after the proteins are denatured, the permeability of the lysosome membrane is increased, the nano-carrier cannot be discharged to the extracellular, the drug concentration in cells is greatly improved, and the drug bioavailability of the nano-carrier is significantly improved; in addition, the drug loading capacity of the nano-carrier is high, and therefore, the nano-carrier has a good application prospect.

The utility model provides a spherical tablet, and belongs to the field of pharmaceutical preparations. The spherical tablet comprises an upper hemisphere, a lower hemisphere and a middle belt, and the middle belt is located in the middle of the spherical tablet and is in a belt shape with the same thickness. The upper hemisphere and the lower hemisphere are located on the two end faces of the middle belt, and the two hemispheres are the same in size and shape. The diameter of the middle zone is larger than the diameter of the hemisphere, the diameter of the hemisphere of an upper stamping die and the diameter of the hemisphere of a lower stamping die of a tablet pressing die adopted when the spherical tablet is pressed ranges from 6.5 mm to 10 mm, and the ratio of the arc depth to the diameter of the hemisphere is (0.2-0.4): 1. The spherical tablet is small in size, easy to swallow, high in drug loading capacity and less in taking quantity; and the tablet has the advantages of good compressibility, good hardness, strong shock resistance and wear resistance, small tablet weight difference, facilitation of later coating and other operations, and good uniformity and reproducibility.

The invention belongs to the technical field of traditional Chinese medicine preparations, and provides a pharmaceutical composition for recurrent urinary tract infection and a preparation method thereof. According to the invention, a compound extract for warming yang, promoting diuresis and activating blood and baicalin are synergistically compounded in an ion composite network formed by sodium alginate and chitosan, and are subjected to shear dispersion or homogenization treatment to form ion composite nanoparticles, and then the ion composite nanoparticles are subjected to calcium chloride cross-linking solidification and chitosan coating to prepare a multi-layer synergistic carrier design of the pellet; the dispersion uniformity, the forming strength, the pH response release and the storage stability of the ionic composite nanoparticles under the condition of high drug loading capacity are realized, and the core contradiction that the mechanical strength, the in-vivo swelling response release and the low-water-content storage and transportation stability are difficult to consider at the same time in the existing calcium alginate carrier system is solved; the method has wide clinical application value in comprehensive prevention and treatment of recurrent urinary tract infection.

The invention discloses a load ICGamp. The invention discloses ZIF-8 nano-particles of CBF, and belongs to the technical field of preparation of nano-drug particles. The multifunctional nanoparticles are formed by simultaneously encapsulating indocyanine green (ICG) and cinobufagin (CBF) components by ZIF-8, and the drug loading capacities of the two drugs are both not lower than 5%. The preparation method comprises the following steps: slowly adding a solution containing cinobufagin and zinc nitrate into a mixed solution containing indocyanine green, bovine serum albumin and 2-methylimidazole, and carrying out centrifugal filtration, washing and drying on a reaction product to obtain the cinobufagin zinc oxide. The multifunctional nano-particles prepared by a one-step synthesis method are uniform in particle size and good in stability, indocyanine green and cinobufagin are uniformly distributed in a carrier, the multifunctional nano-particles have pH and near-infrared light dual response drug release characteristics, triple synergy of chemotherapy, photothermal therapy and photodynamic therapy can be realized, and the multifunctional nano-particles are simple in preparation process and suitable for popularization and application.